**(Novo 7) to patient (X)**

#### **Example of an incident Investigation Incident: Issue of time expired product**

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 263

between order and product availability for use. An SOP is a written document / instruction detailing all steps and activities of a process or procedure. These should be carried out without any deviation or modification to guarantee the expected outcome. Any modification or deviation from a given SOP should be thoroughly investigated and outcomes of the investigation documented according the internal deviation procedure. All quality impacting processes and procedures should be laid out in Standard Operating Procedures (SOPs). These SOPs should be the basis for the routine training program of each employee. SOPs should be available, followed strictly in laboratory analysis and regularly updated to assure compliance to CPA Standard F (Examination process) and sub standard F2 (Examination procedures) requirements. Changes of SOPs are in gen-

eral triggered by process or procedural changes / adjustments.

1. Removed all remaining time expired Novo 7 out from stock to prevent

3. Conveyed advice of consultant Haematologist to consultant managing

4. On advise of the consultant Haematologist, requested an in date unit of

1. Issue of time expired batch product. This observation constitutes a noncompliance to CPA Standard D (Equipment, information system and materials) and sub standard D3 (Management of reagents, calibration and

2. Absence of SOP on inventory control management of batch products. This observation constitutes a non- compliance to CPA Standard F (Examination process) and sub standard F2 (Examination procedures).

3. Inadequate pre and post product allocation checks before issue of batch product. This observation constitutes a non- compliance to CPA Standard F (Examination process) and sub standard F2 (Examination procedure).

**Describe the corrective and preventive action that could be taken to eliminate root cause.** 1. Devise a more effective inventory /stock control system for batch products.

**Describe the immediate remedial action taken to prevent harm to patient:**

2. Rang the transfusion manager on call for advice.

the said patient in the high dependency unit.

the batch product from the nearest sister Hospital.

re-occurrence of incident.

**Non-compliances identified:**

quality control).

#### **Investigator's name: Erhabor Osaro Date of Incident: 3rd April 2010**

**Give brief information of incident.** On the 3rd day of April 2010 a time expired unit of batch product (NOVO 7) was mistakenly issued on a patient in HDU who had post partum haemorrhage and had continued to bleed even after the issue of several units of red cells, adult dose of fresh frozen plasma (FFP) and two units of platelet. The Novo 7 had been requested by the consultant to facilitate the immediate arrest of the life threatening haemorrhage. The discovery that the said batch product expired 4 months ago had been noted by the doctors and nursing staff during the pre- product administration checks by the patient bed side. The reconstitution fluid was however in date.

**State the reasons for identifying this learning.** I had identified this learning (incident) with the aim of carrying out a full investigation of the incident with the hope of determining the root causes, suggesting corrective and preventive measures to prevent the root causes, instigating policy and procedural changes and to enhance our drive as a department for continuous quality improvement.

#### **Describe the root causes of this incident.**


between order and product availability for use. An SOP is a written document / instruction detailing all steps and activities of a process or procedure. These should be carried out without any deviation or modification to guarantee the expected outcome. Any modification or deviation from a given SOP should be thoroughly investigated and outcomes of the investigation documented according the internal deviation procedure. All quality impacting processes and procedures should be laid out in Standard Operating Procedures (SOPs). These SOPs should be the basis for the routine training program of each employee. SOPs should be available, followed strictly in laboratory analysis and regularly updated to assure compliance to CPA Standard F (Examination process) and sub standard F2 (Examination procedures) requirements. Changes of SOPs are in general triggered by process or procedural changes / adjustments.

### **Describe the immediate remedial action taken to prevent harm to patient:**


### **Non-compliances identified:**

262 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

10. Blood administration errors

greater than 30 minutes.

for transplant).

blood products.

reconstitution fluid was however in date.

**Describe the root causes of this incident.**

ous quality improvement.

product.

**(Novo 7) to patient (X)**

9. Blood transfusion reaction and other transfusion-related adverse events.

11. Issue of wrong component/specification (for example Kell positive unit given to woman of child bearing age, CMV positive unit transfused to HIV or immunocompromised patient and transfusion of non-irradiated blood and blood product for patient in whom it is indicated (patient on purine analogue chemotherapy and patient who are potential candidates

12. Poor/inappriopriate component storage issues such as storage of platelet in the fridge and transfusion of units that has been out of cold storage for

13. Blood component quality problems such as bacterial contamination of

**Example of an incident Investigation Incident: Issue of time expired product** 

**Give brief information of incident.** On the 3rd day of April 2010 a time expired unit of batch product (NOVO 7) was mistakenly issued on a patient in HDU who had post partum haemorrhage and had continued to bleed even after the issue of several units of red cells, adult dose of fresh frozen plasma (FFP) and two units of platelet. The Novo 7 had been requested by the consultant to facilitate the immediate arrest of the life threatening haemorrhage. The discovery that the said batch product expired 4 months ago had been noted by the doctors and nursing staff during the pre- product administration checks by the patient bed side. The

**State the reasons for identifying this learning.** I had identified this learning (incident) with the aim of carrying out a full investigation of the incident with the hope of determining the root causes, suggesting corrective and preventive measures to prevent the root causes, instigating policy and procedural changes and to enhance our drive as a department for continu-

1. Poor inventory/stock control management of batch product (Novo 7).

2. Inadequate pre and post product allocation checks before issue of batch

3. Absence of SOP on inventory control management of batch products stipulating minimum, maximum and re-order level as well as lead time

**Investigator's name: Erhabor Osaro Date of Incident: 3rd April 2010**


#### **Describe the corrective and preventive action that could be taken to eliminate root cause.**

1. Devise a more effective inventory /stock control system for batch products.

2. Draw up a standard operating procedure inventory /stock control system for batch products.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 265

If our aim is to detect the presence of antibody in the plasma or serum, we react the plasma/ serum against red cell panel containing known antigen to facillitae the identification of the corresponding antibody in the plasma. This reaction is based on the principle that antigen

**Sources of Antigen Testing.** In almost all blood bank techniques we have red cells with antigens present. These red cells may either be reagent red cells with known antigens, patient red cells, or donor red cells. The reagent red cells are commercially prepared and have all the red cell antigens identified. When we use red cells where the antigens have already been determined, we can identify the possible antibodies present. A1 and B cells for confirmation of the ABO type in all patients and donors other than newborn babies. Antibody screening cells are O cells that have been studied to determine the presence of a number of antigens for specific antibodies that are known to cause transfusion reactions and hemolytic disease of the newborn. The antibody screening technique is part of all compatibility tests done before blood is transfused. Some of the more common antibodies detected are anti-D, anti-E and anti-K. Antibody identification cell panel are again O cells with the specific antigens known. Usually there are between 8 and 12 different cells in a cell panel. The pattern of positive and

**Sources of Antibody for Testing.** Antibody is found in serum. If it is the patient's serum that is being tested, we do not know what antibody may be present so we are using one of the 3 types of reagent cells listed above. If the serum is commercial reagent, the specific antibody present is already known. The commercial serum reagent is referred to as antisera. Therefore, we use Anti-A antisera to determine if a patient or donor has antigen A on his red cells. If we are trying to determine if the patient is Rh + or Rh -, we will use anti-Rho (D) antisera. Table 1

**gen or antibody Source with known component Source with unknown component**

Antigen Reagent Red Blood Cells Patient or Donor red blood cells

Antibody Commercial Antisera Patient or donors plasma/serum

**Testing procedures routinely done in blood banking.** In a transfusion service there are a number of procedures routinely done. They include; ABO/Rh(D) typing, antigen typing from other blood group systems such as Rh antigens other than D, Kell, Kidd, and Duffy, allontibody screening for antibodies formed to blood group antigens other than A and B, alloantibody identification to determine the specificity of the antibodies detected in the antibody screening to allow for the selection of antigen negative red cells for transfusion, crossmatch, or compatibility testing, which determines whether donor blood can probably be safely transfused to the recipient. Other procedures include determination of Direct and indirect antihuman globulin test,

Table: Sources of known and unknown antigen red cells and antibody plasma/ serum reagents

is a summary of known and unknown sources of both antigens and antibodies.

and antibody reaction are specific.

negative reactions helps identify the antibody.

**Source of anti-**


### **42. Laboratory techniques and transfusion sample requirements**

**Blood banking reagents.** The techniques used in blood bank involve mixing/reacting antigens, usually on red blood cells with antibodies. The environment where this reaction occurs can range in temperature from 4°C to 37°C. With the most common being room temperature for ABO and the initial Rh(D) testing and 37°C when screening and identifying other clinically significant antigen-antibody reactions. Situations for testing in the blood bank range from determination of antigens on the red cell (A or B antigens to determine a patient's ABO type and to determine the Rhesus group) to looking for particular antibodies that may cause transfusion reactions or hemolytic disease of the newborn. Depending on whether we are looking for a particular antigen or antibody will determine what reagents we are going to use. If we are looking for an antigen on a patient's red cells, we will use known antibody containing the group specific antibody that will cause agglutination of the antigens on the red cells. If our aim is to detect the presence of antibody in the plasma or serum, we react the plasma/ serum against red cell panel containing known antigen to facillitae the identification of the corresponding antibody in the plasma. This reaction is based on the principle that antigen and antibody reaction are specific.

264 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

for batch products.

diluents.

new SOP.

(Novo 7).

been eliminated.

2. Draw up a standard operating procedure inventory /stock control system

3. Train all employees carrying out the specific activity on the SOP and get them to sign the SOP as an attestation that they are aware of the presence of a standard procedure for the task and that they will continue to carry

4. Re-iterate in the continuous improvement meetings held every morning the need to do a pre and post batch product allocation checks before des-

5. State the steps that should be taken to implement the corrective actions arising from this investigation and how lessons learnt from this incident

6. Amend SOP on issue of batch products (Novo 7) to reflect suggested change with regards to separating the batch product (Novo 7) from the

7. Communicate change to all staff performing task by way of training on

8. Devise a more effective inventory control measure for batch products

9. Draw up an SOP on inventory control management of batch products.

**42. Laboratory techniques and transfusion sample requirements** 

10. Review process in the next 3 months to ensure that the root causes has

**Blood banking reagents.** The techniques used in blood bank involve mixing/reacting antigens, usually on red blood cells with antibodies. The environment where this reaction occurs can range in temperature from 4°C to 37°C. With the most common being room temperature for ABO and the initial Rh(D) testing and 37°C when screening and identifying other clinically significant antigen-antibody reactions. Situations for testing in the blood bank range from determination of antigens on the red cell (A or B antigens to determine a patient's ABO type and to determine the Rhesus group) to looking for particular antibodies that may cause transfusion reactions or hemolytic disease of the newborn. Depending on whether we are looking for a particular antigen or antibody will determine what reagents we are going to use. If we are looking for an antigen on a patient's red cells, we will use known antibody containing the group specific antibody that will cause agglutination of the antigens on the red cells.

enhanced the department quest for continuous improvement?

out the task based on the Standard operating procedure.

patching products to the wards or satellite fridges.

**Sources of Antigen Testing.** In almost all blood bank techniques we have red cells with antigens present. These red cells may either be reagent red cells with known antigens, patient red cells, or donor red cells. The reagent red cells are commercially prepared and have all the red cell antigens identified. When we use red cells where the antigens have already been determined, we can identify the possible antibodies present. A1 and B cells for confirmation of the ABO type in all patients and donors other than newborn babies. Antibody screening cells are O cells that have been studied to determine the presence of a number of antigens for specific antibodies that are known to cause transfusion reactions and hemolytic disease of the newborn. The antibody screening technique is part of all compatibility tests done before blood is transfused. Some of the more common antibodies detected are anti-D, anti-E and anti-K. Antibody identification cell panel are again O cells with the specific antigens known. Usually there are between 8 and 12 different cells in a cell panel. The pattern of positive and negative reactions helps identify the antibody.

**Sources of Antibody for Testing.** Antibody is found in serum. If it is the patient's serum that is being tested, we do not know what antibody may be present so we are using one of the 3 types of reagent cells listed above. If the serum is commercial reagent, the specific antibody present is already known. The commercial serum reagent is referred to as antisera. Therefore, we use Anti-A antisera to determine if a patient or donor has antigen A on his red cells. If we are trying to determine if the patient is Rh + or Rh -, we will use anti-Rho (D) antisera. Table 1 is a summary of known and unknown sources of both antigens and antibodies.


Table: Sources of known and unknown antigen red cells and antibody plasma/ serum reagents

**Testing procedures routinely done in blood banking.** In a transfusion service there are a number of procedures routinely done. They include; ABO/Rh(D) typing, antigen typing from other blood group systems such as Rh antigens other than D, Kell, Kidd, and Duffy, allontibody screening for antibodies formed to blood group antigens other than A and B, alloantibody identification to determine the specificity of the antibodies detected in the antibody screening to allow for the selection of antigen negative red cells for transfusion, crossmatch, or compatibility testing, which determines whether donor blood can probably be safely transfused to the recipient. Other procedures include determination of Direct and indirect antihuman globulin test, dtermination of feto maternal haemorrhage (FMH), issue of prophylactic anti-D to pregnant rhesus negative women or following potentially sensitising event in pregnancy.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 267

**Grading Agglutination Reactions.** Swirling off. A fine suspension indicates a negative reaction. Agglutination in chunks indicates a positive reaction. Continue shaking till all cells resuspended. Tilt tube, read and grade reaction. Solid agglutination clump is graded as 4+, several large clumps as 3+, small to medium sized clumps on a clear background as 2+, small clumps with cloudy background as 1+ and tiny aggregates with cloudy background as 0.5+. Sometimes agglutination can be observed microscopically and can either be positive upon microscopic examination or negative. Observation of small clumps amidst many unagglutinated cells is called mixed field reaction (MF). Haemolyzed reaction is indicative of a positive reaction. If no agglutination, the test is said to be negative. It is not advisable to use (**-**) to represent a negative reaction as it may be mis-understood. Rather it is more appriopriate to use either **Neg or 0**.

**Preparation of red cells suspension.** Between 2-5% cell suspension provides optimum antigen concentration for the tube method for red blood cells typing. To make sure your suspen-

**Washing red blood cells prior to preparing the 3% suspension**. The purpose of washing the red blood cells is to remove plasma, which contains substance that may interfere with antigen-antibody reaction. The following may be in the plasma and may interfere with testing. Such substances include; soluble antigens such as A and B may be present and neutralize your reagent, interfering proteins such as Wharton's jelly that is seen in newborn cord blood, cold-acting autoimmune antibodies and increased levels of immunoglobulins that may cause either agglutination or rouleaux, haemolyzed red blood cells due to a difficult draw will interfere in your grading interpretation and fibrinogen can result in fibrin strands forming that

**Good technique in preparation of a 3% cell suspension involves the following**

sion is within this range use reagent red cells for comparison.

1. Place 1 to 3 drops of blood in the tube

makes grading reactions difficult.


Summary the sources of both the antigen and antibody

#### **Grading agglutination reactions in the blood transfusion laboratory**

Grading agglutination reactions gives an indication of the relative amount of antigen or antibody present. All tubes tests should be graded. The technique used in the resuspension of the cells will affect the grading of the reaction. The correct procedure for resuspending and grading reactions includes;


Figure : Example of lighted agglutination viewer

**Grading Agglutination Reactions.** Swirling off. A fine suspension indicates a negative reaction. Agglutination in chunks indicates a positive reaction. Continue shaking till all cells resuspended. Tilt tube, read and grade reaction. Solid agglutination clump is graded as 4+, several large clumps as 3+, small to medium sized clumps on a clear background as 2+, small clumps with cloudy background as 1+ and tiny aggregates with cloudy background as 0.5+. Sometimes agglutination can be observed microscopically and can either be positive upon microscopic examination or negative. Observation of small clumps amidst many unagglutinated cells is called mixed field reaction (MF). Haemolyzed reaction is indicative of a positive reaction. If no agglutination, the test is said to be negative. It is not advisable to use (**-**) to represent a negative reaction as it may be mis-understood. Rather it is more appriopriate to use either **Neg or 0**.

266 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

Antigen typing

Antibody screening

Compatibility testing or Crossmatch

cludes;

Antibody identification Identifies the specificity

Summary the sources of both the antigen and antibody

1. Use lighted agglutination viewer 2. Read only one tube at a time

3. Hold tube upright

Figure : Example of lighted agglutination viewer

dtermination of feto maternal haemorrhage (FMH), issue of prophylactic anti-D to pregnant

**Procedure Purpose Source of antigen Source of antibody**  ABO/Rh typing Detects A, B, and D Patient's RBC's Commercial anti-A,

> Patient's RBC's or Donor RBC's

Commercial Screening

of RBC antibodies Commercial panel cells Patient's serum

anti-B, and anti-D

Commercial antisera to the specific antigens (examples: anti-K, anti-E, anti-C, anti-Fya and anti-Jka).

Cells Patient's serum

Donor RBC's Patient's serum

rhesus negative women or following potentially sensitising event in pregnancy.

Detects antigens of other blood group systems (examples: K, E, C, Fya, Jka)

Detects antibodies with specificity of RBC antigens

Determines serologic compatibility between donor and patient before transfusion

**Grading agglutination reactions in the blood transfusion laboratory** 

4. Position cell button so it is facing you in the mirror

Grading agglutination reactions gives an indication of the relative amount of antigen or antibody present. All tubes tests should be graded. The technique used in the resuspension of the cells will affect the grading of the reaction. The correct procedure for resuspending and grading reactions in-

5. Very gently shake the tube and observe how the cells come off the cell button

**Preparation of red cells suspension.** Between 2-5% cell suspension provides optimum antigen concentration for the tube method for red blood cells typing. To make sure your suspension is within this range use reagent red cells for comparison.

**Washing red blood cells prior to preparing the 3% suspension**. The purpose of washing the red blood cells is to remove plasma, which contains substance that may interfere with antigen-antibody reaction. The following may be in the plasma and may interfere with testing. Such substances include; soluble antigens such as A and B may be present and neutralize your reagent, interfering proteins such as Wharton's jelly that is seen in newborn cord blood, cold-acting autoimmune antibodies and increased levels of immunoglobulins that may cause either agglutination or rouleaux, haemolyzed red blood cells due to a difficult draw will interfere in your grading interpretation and fibrinogen can result in fibrin strands forming that makes grading reactions difficult.

### **Good technique in preparation of a 3% cell suspension involves the following**

1. Place 1 to 3 drops of blood in the tube

2. Aim the tip of the saline bottle towards the center of the tube and forcibly squirt saline into the tube.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 269

number, estimated date of birth and name (for example Unknown Male) and blood specimen must also be discarded when both name and medical record number have changed (example: Erhabor Osaro and Hospital number 1365200 becomes Adias Teddy Charles 1423562).

**Double bedside Check Procedure before transfusion.** All patients to be transfused must have a wrist band. Details on the unit intended for transfusion must be checked by 2 nursing staff against the prescription and the patient medical notes. The following must be checked; surname, first name, hospital number, date of birth, blood group on the unit and patients blood group, donor number and expiry and suitability date. Finally check the wrist band to

**Administration of Blood component**. Registered doctors, midwives, nurses and ODP's can administer blood. All transfusion must be prescribed on a transfusion record transcription. Drugs and other fluids **must not** be added to blood component or infused through the same cannula simultaneously. A blood giving set with a filter must be used to transfuse blood component. A drip giving set **must never** be used to transfuse blood component. The right sized cannula appriopriate for the size of the vein and the rate of transfusion must be used. The cannula must be flushed with 2-5ml of 0.9% saline pre and post transfusion. Red cell can be warmed prior to ensure that it attain ambient temperature to prevent hypotherma. Patient should be kept warm during the transfusion. Vital signs ( temperature, blood pressure and pulse must be recorded before commencing transfusion and after the first 15 minutes of commencing transfusion, following any adverse events during transfusion and after each unit is transfused. There is no need to prime with saline before connecting the blood and there is no need to flush with saline after the residual volume is minimal. The blood giving set must be replaced after every 12 hours (after every 2-3 red cells, after a dose of FFP is given (4 units) and after 1-2 units of platelets) and when a different blood component type or fluid is being commenced. A unit of red cell must be transfused over 2-3 hours. Unit must be discarded after 4 hours. A unit of FFP or platelet is transfused over 30 minutes. If transfusion reaction is observed (mild febrile reaction with temperature < 38°C) review and give paracetamol and recommence transfusion but at a slow rate and observe. If symptom resolve, there is no need to report to transfusion laboratory. However one must be cautious if patient is neutropenic. If symptom do not resolve, stop the transfusion, report to transfusion laboratory for investigation of transfusion reaction. If urticaria, itching, wheals confirmed to the skin is observed, review patient and give piriton or hydrocortisone, slow down the transfusion and observe more frequently. If symptom do not resolve, stop the transfusion, report to transfusion laboratory for investigation of transfusion reaction. If there is severe transfusin reaction; fever >38°C with other symptoms such as rigors, flushing, restlessness, dyspnoea, headache, pain at infusion site, respiratory distress, loin and back pain, hypotension, tachycardia, haemoglobinuria, unexpected bleeding (DIC), anaphylaxis/haemolytic incompatible wrong blood incident, bacteremic shock and TRALI, the blood must be stopped, check the patient and unit ID, infuse normal saline to maintain systolic blood pressure, inform the transfusion laboratory and send reminant of unit and giving set, samples for blood culture on the patient and from sample taken from the blood bag, post transfusion blood

ensure that the unit is being transfused to the intended patient.

and urine sample to enable the investigation of the transfusion reaction.


**Sample Requirement in Blood Transfusion.** Most samples for blood banking are drawn into an Ethylene Diamine Tetra Acetic Acid (red top tube). A few tests require an EDTA sample if complement is not to be activated. Serum must be tested while fresh to ensure good complement activity. Antigens on cells are stable longer (months) in a clot tube.

**Patient Identification.** The patient MUST be positively identified and preferably wrist banded. Some institutions use specific blood bank arm bands. Ask patient to state his/her name and date of birth. Responsible party should identify patient if he/she cannot. Verify information by comparing it to ID wrist band and ensuring that it matches what is on the request form. Resolve any differences before proceeding with the blood draw.

**Labeling of Sample.** The information on sample must match information on ID band, which would also need to be consistent with the order. Information on samples must be hand written (addressograph label is not allowed on a transfusion sample) must include the following; sample drawn should be 7.5 ml EDTA sample, name (last, first, middle initial) and no nicknames, unique identification number such as hospital number or medical record number or possibly social security number, ward, date and time sample drawn along with the signature or unique identifier of phlebotomist (on sample and on orders), gender and birthdate desirable but not mandatory. The date of birth provides another unique identifier along with the medical record number and full name of the patient. All unknown or unconscious patients admitted into Accident and Emergency (A&E) must be given a unique A&E identification number and an estimated date of birth until patient can be properly identified, sample labelling must be done at the patient bed side as one continuous uninterrupted process, mislabeled samples must not be accepted and all samples must be properly labeled. The following are what would warrant an improperly labeled specimen; missing information (Date of birth, hospital number, name), incorrect information (incorrectly spelt name, incorrect date of birth and incorrect hospital number), information on sample not matching information on orders, sample not signed by requesting clinician, unlabelled/ improperly labeled samples must be discarded if the problem cannot be resolved. In the case of an emergency blood drawn on a patient who is unidentified at that time can be tested but must have a unique identifier (A&E

number, estimated date of birth and name (for example Unknown Male) and blood specimen must also be discarded when both name and medical record number have changed (example: Erhabor Osaro and Hospital number 1365200 becomes Adias Teddy Charles 1423562).

268 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

squirt saline into the tube.

5. Decant the saline completely.

ing are going to be done.

tom of the tube.

2. Aim the tip of the saline bottle towards the center of the tube and forcibly

3. Fill the tube 3/4 full of saline (there will be less splattering in the centrifuge)

4. Centrifuge long enough spin to pull most of cells into a button in the bot-

6. Shake the tube to resuspend cell button before washing the cells again. It will depend on the procedure being done as to how many types of wash-

**Sample Requirement in Blood Transfusion.** Most samples for blood banking are drawn into an Ethylene Diamine Tetra Acetic Acid (red top tube). A few tests require an EDTA sample if complement is not to be activated. Serum must be tested while fresh to ensure good comple-

**Patient Identification.** The patient MUST be positively identified and preferably wrist banded. Some institutions use specific blood bank arm bands. Ask patient to state his/her name and date of birth. Responsible party should identify patient if he/she cannot. Verify information by comparing it to ID wrist band and ensuring that it matches what is on the request

**Labeling of Sample.** The information on sample must match information on ID band, which would also need to be consistent with the order. Information on samples must be hand written (addressograph label is not allowed on a transfusion sample) must include the following; sample drawn should be 7.5 ml EDTA sample, name (last, first, middle initial) and no nicknames, unique identification number such as hospital number or medical record number or possibly social security number, ward, date and time sample drawn along with the signature or unique identifier of phlebotomist (on sample and on orders), gender and birthdate desirable but not mandatory. The date of birth provides another unique identifier along with the medical record number and full name of the patient. All unknown or unconscious patients admitted into Accident and Emergency (A&E) must be given a unique A&E identification number and an estimated date of birth until patient can be properly identified, sample labelling must be done at the patient bed side as one continuous uninterrupted process, mislabeled samples must not be accepted and all samples must be properly labeled. The following are what would warrant an improperly labeled specimen; missing information (Date of birth, hospital number, name), incorrect information (incorrectly spelt name, incorrect date of birth and incorrect hospital number), information on sample not matching information on orders, sample not signed by requesting clinician, unlabelled/ improperly labeled samples must be discarded if the problem cannot be resolved. In the case of an emergency blood drawn on a patient who is unidentified at that time can be tested but must have a unique identifier (A&E

ment activity. Antigens on cells are stable longer (months) in a clot tube.

form. Resolve any differences before proceeding with the blood draw.

**Double bedside Check Procedure before transfusion.** All patients to be transfused must have a wrist band. Details on the unit intended for transfusion must be checked by 2 nursing staff against the prescription and the patient medical notes. The following must be checked; surname, first name, hospital number, date of birth, blood group on the unit and patients blood group, donor number and expiry and suitability date. Finally check the wrist band to ensure that the unit is being transfused to the intended patient.

**Administration of Blood component**. Registered doctors, midwives, nurses and ODP's can administer blood. All transfusion must be prescribed on a transfusion record transcription. Drugs and other fluids **must not** be added to blood component or infused through the same cannula simultaneously. A blood giving set with a filter must be used to transfuse blood component. A drip giving set **must never** be used to transfuse blood component. The right sized cannula appriopriate for the size of the vein and the rate of transfusion must be used. The cannula must be flushed with 2-5ml of 0.9% saline pre and post transfusion. Red cell can be warmed prior to ensure that it attain ambient temperature to prevent hypotherma. Patient should be kept warm during the transfusion. Vital signs ( temperature, blood pressure and pulse must be recorded before commencing transfusion and after the first 15 minutes of commencing transfusion, following any adverse events during transfusion and after each unit is transfused. There is no need to prime with saline before connecting the blood and there is no need to flush with saline after the residual volume is minimal. The blood giving set must be replaced after every 12 hours (after every 2-3 red cells, after a dose of FFP is given (4 units) and after 1-2 units of platelets) and when a different blood component type or fluid is being commenced. A unit of red cell must be transfused over 2-3 hours. Unit must be discarded after 4 hours. A unit of FFP or platelet is transfused over 30 minutes. If transfusion reaction is observed (mild febrile reaction with temperature < 38°C) review and give paracetamol and recommence transfusion but at a slow rate and observe. If symptom resolve, there is no need to report to transfusion laboratory. However one must be cautious if patient is neutropenic. If symptom do not resolve, stop the transfusion, report to transfusion laboratory for investigation of transfusion reaction. If urticaria, itching, wheals confirmed to the skin is observed, review patient and give piriton or hydrocortisone, slow down the transfusion and observe more frequently. If symptom do not resolve, stop the transfusion, report to transfusion laboratory for investigation of transfusion reaction. If there is severe transfusin reaction; fever >38°C with other symptoms such as rigors, flushing, restlessness, dyspnoea, headache, pain at infusion site, respiratory distress, loin and back pain, hypotension, tachycardia, haemoglobinuria, unexpected bleeding (DIC), anaphylaxis/haemolytic incompatible wrong blood incident, bacteremic shock and TRALI, the blood must be stopped, check the patient and unit ID, infuse normal saline to maintain systolic blood pressure, inform the transfusion laboratory and send reminant of unit and giving set, samples for blood culture on the patient and from sample taken from the blood bag, post transfusion blood and urine sample to enable the investigation of the transfusion reaction.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 271

Take blood sample and correctly label at patient bed side

Complete the request/electronic order form correctly

Send the sample and request form to the Blood Bank

Determine patient's ABO and RhD type

Detect clinically significant red cell antibodies

Select and crossmatch appriopriate red cell units

Check labelling & ensure it match patient identifiers

Maintain correct storage conditions until transfusion

Deliver to appropriate person in clinical area

Record removal of unit from storage location

Carry out antibody screen on patient sample

Apply compatibility label

Communicate with Blood Bank if blood is required urgently

Take note of special transfusion requirements

*Cirical issues to remember when ordering blood component*

**Process to consider during pretransfusion testing**

**Things to consider delivering blood component ward**

Identify the patient correctly

#### **Pre-transfusion investigation of a patient's blood sample**

270 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

**Pre-transfusion investigation of a patient's blood sample**

**Clinical blood transfusion process**

**Issues to consider in deciding to transfuse a patient**

Repeat test on primary sample with contols

Check for possible effect of diagnosis and race

Check sample integrity and reagents (expiration) haemolysis)

**Resolution of discrepancy in ABO grouping**

Monitor patient

Blood component is delivered

Assess clinical condition

Record the decision and rationale

Obtain consent from patient

Carry out pre-transfusion test and checks

Order clinically indicated blood component/s

Decide based on clinical and lab evidence whether to transfuse

Pre-transfusion checks done and component transfused

Monitor patient for adverse transfusion-related event

Inform patient about transfusion and why it is required

Use clinical guidelines & ensure it is indicated

Repeat test with fresh sample

Check samples (name, hospital number & DOB) Check samples (name, hospital number & DOB)

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 273

**Reasons why things goes wrong**

Lack of transfusion knowledge or failure to follow guidelines

Inadequate clinical Assessment

Unaware of importance of information and

consent

No patient information Available

Information given at wrong time

read or understand information

**Prevention and precautions**

Ensure that clinical guidelines are available.

Ensure that guidiance are strictly complied with and that they are regularly audited.

Ensure that the prescriber has a thorough knowledge of the indications for blood components and the knowledge to answer Patient's questions.

Written patient information is provided, at right time and is legible and understandable.

Consent must be recorded.

Compliance with procedures is audited

and reactions are investigated

Ensures that procedures improved by lessons learned from root cause analysis of errors and near misses.

**Consequences to patient**

Avoidable exposure to infection or immunological risk

Risk of myocardial ischemia

Patient makes complaint

No record available to defend medicolegal challenge

Wrong dose given Patient couldn't

Patient not informed Errors, events

Transfusion associated circulatory overload

**Steps in the process**

Assess clinical condition

Decide if transfusion is indicated, which component and how many units to

give

**What can go wrong**

Wrong clinical decision

Unnecessary transfusion

necessary transfusion

Wrong component

given

 Decision not recorded

Discuss with patient Failure to give a

Obtain consent Patient case record lost

Record indication for transfusion and the discussion with

patient

Essentials of patient monitoring transfused patient


272 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

Identify the patient correctly

Record pretransfusion vital signs

Check unit for expiry date

Complete all documentation

*Patient monitoring in a patient being transfused*

Recognise, diagnose and respond quickly to adverse event

Essentials of patient monitoring transfused patient

Ensure there is a written instruction to transfuse

Check patients group & ensure it is compatible with component

Repeat check of patient identification against component

Inspect components for signs of contamination and leakages

Set rate of transfusion according to instructions

Get a 2nd nursing staff to cross check patient & component details

Record outcome of transfusion Assess need for further transfusion

*Essentials of administering blood components*

Monitor patient's vital signs regularly

#### Clinical Decision toTransfuse


Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 275

**Why things go wrong**

Sample transport inappriopriate for crossmatch.

Ignorance of major haemorrhage procedure (MHP) and no MHP available.

**Why things go wrong**

Failure of communication

Reluctance of transfusion lab to issue uncrossmatched

unit to transfuse uncrossmatched red

red cells.

cells.

Delayed transfusion. Reluctance of clinical

**Prevention/ precautionary measures**

(drill).

Major haemorrhage procedure must be practised periodically

Procedures must be audited regularly to ensure compliance to statutory requirement.

All error, events, near misses and reactions must be investigated and corrective actions put in place. Procedures must be improved from lesion learnt from error, events, near misses and reactions.

**Prevetion/ precautions**

Major haemorrhage procedure should specify how urgent request are communicated.

Blood bank must insist on correct identification and a fresh sample if necessary.

Staff performing task must be trained and competency tested.

**Consequences to the patient**

Death or serious complication due to delayed transfusion.

Table: Analysis and prevention of errors in ordering blood components (Patient Sample and Request for Blood)

Delayed transfusionrelated risk of exsanguination.

Risk of incompatible transfusion due to mistaken identification.

**patient**

**Steps in the process What can possibly** 

If a major haemorrhage, initiate a major haemorrhage procedure (MHP).

Note urgency of request. If in doubt confirm from requesting clinician.

Select appriopriate procedure for level of

Check that patient ID on sample match what is on form and that both contains the minmum data set.

urgency.

**go wrong**

Failure to recongnise major haemorrhage.

Failure to activate major haemorrhage

**Steps in process What can go wrong Consequences on** 

Urgency misunderstood

Inappriopriate procedure selected.

Patient sample and request form not checked. For consistency and completeness

procedure.


274 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

**Consequences to the patient**

Immunosuppressed patient put at risk of

Delayed haemolytic blood transfusion

GVHD

reaction.

Young Rhesus negative female of child bearing age sensitized to produce immune anti-D by transfusing Rh positive unit.

Elderly patient transfused with wrong component (cryoprecipitate instead of FFP) or quantity (TACO).

Fatal ABO incompatibility reaction

**Why things go wrong**

Inadequate information on form.

Request form completed incorrectly.

Incorrect details on

Correct patient but sample tube wrongly

Sample taken from wrong patient.

sample.

labelled.

**Prevention/ precautionary measures**

Patient identification policy must be in place and being complied with.

Manimum data set for patient ID must be in place and being followed.

Prescriber must be trained on pretransfusion sample requirement and request form.

Prescriber must be aware of indication for particular components (CMV negative, irradiated, Kell negative units) and order component correctly.

Laboratory staff and transport staff 9porters) must be trained on major haemorrhage procedure.

Clinical Decision toTransfuse

Correctly identify the

patient

Decide which component is needed and the quantity.

Complete blood request form.

Take pre-transfusion sample and label at patient bedside. Addressograph label is not acceptable.

Send blood sample and request to blood

bank

**Steps in the process What can possibly** 

**go wrong**

Failure to communicate special transfusion requirements for example CMV negative or irradiated component

Incorrect blood group in the patient

Inappriopriate dose or volume requested.

Patient receives unit meant for another

patient.

record.

Pretransfusion sample taken from the wrong patient.

Table: Analysis and prevention of errors in ordering blood components (Patient Sample and Request for Blood)



Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 277

**Why things go wrong**

delivered.

storage.

Clinical staff not aware that units have been

Component discarded due to inappriopriate

Blood unit wasted Errors, events, near

**Why things go wrong**

Decolouration or change in colour of component not noticed.

Expired pack not identified.

Check of patient and unit details not

Instruction on rate of transfusion not clear and not followed.

checked.

**Prevention/ precaution**

All procedures (SOP) must be documented

Compliance to procedures must be audited regularly.

misses must be investigated. Lessons learnt must be used as a learning process to improve procedures

**Prevention/ precaution**

policy must be in place and bedside check must be observed.

Minumum data set for patient ID must be in place and observed.

Staff responsible for administering blood must be trained and competency tested.

All Standard operating procedures must be documented and followed strictly.

Compliance to standard procedure must be audited regularly for compliance.

Pack not inspected. Patient identification

**Steps in the process What can go wrong Consequences for** 

Delay in supplying

Blood delivered to the wrong location.

Blood discarded due to incorrect storage condition.

Wrong storage for example red cell placed in fridge or left in platelet storage area.

**Steps in the process What can go wrong Consequences for** 

Contaminated pack not detected

Outdated pack not detected

Patient receives incorrect component.

Component transfused too quickly.

Analysis and prevention of errors in delivering blood to the clinical area

blood

Blood component received in clinical

Blood component stored correctly until transfused.

Check patient identity

details.

order.

unit

Check written prescription

Ensure IV line is in

Take baseline observation.

Inspect contidion of

araea

**the patient**

anaemia.

Uncorrected severe

Increased risk of transfusion of blood to wrong patient.

Transfusion reaction due to contaminated or thermally damaged

blood

**the patient**

Death due to contamination of contaminated unit.

Morbidity due to transfusion of haemolysed and outdated component.

Death due to ABO incompatibility.

Transfusion associated cardiac overload (TACO).

sepsis

Delay of transfusion Transfusion-related

#### Table: Analysis and prevention of errors in pretransfusion testing



Analysis and prevention of errors in delivering blood to the clinical area

276 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

**Steps in process What can go wrong Consequences on** 

Requesting clinician does not specify special requirement.

Blood bank staff does not register the requirement.

Error in testing and recording of results

Failure to check previous report or

Table: Analysis and prevention of errors in pretransfusion testing

**the patient**

reaction.

haemolytic transfusion

Delayed haemolytic transfusion.

Wrong unit selected Fatal and serious

**Steps in the process What can go wrong Consequences for** 

One or more patient receives an incorrect blood component.

record. Failure to select appriopriate component and despatch of unit to wrong destination or using inappriopriate transport method

Note any specific requirement (CMV negative, irradiated

Determine patient ABO, Rh group as well as antibody screen to detect presence of alloantibodies to enable the selection of antigen negative units.

Confirm that result of ABO and Rh group matches previous laboratory records.

Select appriopriate unit and carry out compatibility testing.

Label, record and dispatch selected units.

Pick up blood component from storage site.

Deliver blood component promptly to clinical area.

units).

**patient**

Delayed haemolytic transfusion reaction due to missed alloantibody.

**Why things go wrong**

with SOP.

Risk of GVHD. Poor training of staff Install effective

No SOP, failure by reqesting clinical staff, use of defective reagents and equipment.

Inadequate records system in blood bank and suitable units not

No SOP, failure by reqesting clinical staff, use of defective reagents and equipment.

Inadequate records system in blood bank and suitable units not

available.

available.

**Why things go wrong**

Patient details not used to select blood unit from storage.

Delivery of blood to wrong location.

Staff failure to comply

**Prevetion/ precautions**

Blood bank must carry out internal qualiy control and participate in EQA programme.

computerised record system and train staff. There should be in place a paper back-up should the computer system fail.

Maintain appriopriate stock levels of blood component, reagents and consumables.

**Prevention/ precaution**

Staff collecting unit from fridge must go with patient ID.

Staff collecting blood from fridge must be trained and competency tested.



Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 279

**Why things go wrong**

for.

respond. Clinician does not treat patient's reaction

correctly.

Clinical help not called

Clinician called fails to

**Prevention/precau-**

Procedures must be improved by lessons learnt from the investigation of transfusion

**tions**

events.

**Steps in process What can go wrong Consequences on** 

Delayed in assessing continued transfusion requirement.

Analysis and prevention of errors in monitoring the transfused patient

Transfusion practitioners must be able to:

ality and informed consent.

burdens, and risks involved.

**43. Principle of informed consent in transfusion medicine**

Assess need for further

transfusion.

**patient**

Incomplete follow up of investigation.

Incomplete transfusion records and non-compliance to legal and statutory requirement.

This topic will help transfusion practitioners understand the principles of patient confidentiality and the need for informed consent, understand the policies regarding informed consent for service users, know how to follow standard operational procedures to take and obtain informed consent, understand that it is part of their duty of care as health professional and that they are accountable for the release of information on a client or patient, understand that if patients or client´s record need to be used to help student gain the knowledge and skills which they require or for research purposes, the same principle of informed consent applies.

1. Practice within local policy and procedures regarding patient confidenti-

2. Practice within national and local policies regarding informed consent.

4. Carry out your professional duties and responsibilities appreciating the need to obtain explicit consent from a patient or client before disclosing specific information as well as understand that the client or patient can make an

informed consent as to whether the information should be disclosed.

5. Carry out your professional duties and responsibilities appreciating the fact that it is the right and responsibility of every competent individual to advance his or her own welfare. This right and responsibility is exercised by freely and voluntarily consenting or refusing consent to recommended medical procedures, based on a sufficient knowledge of the benefits,

6. Treat with discretion the confidential information about patient or client and ensure that they are used for the purposes for which it was intended

3. Demonstrate the policies as they apply to diagnostic service users.

Table: Analysis and prevention of errors in administering blood



Analysis and prevention of errors in monitoring the transfused patient

278 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

**Steps in the process What can go wrong Consequences for** 

Table: Analysis and prevention of errors in administering blood

**Steps in process What can go wrong Consequences on** 

Adverse reaction not

Adverse reaction not managed correctly.

Delay in obtaining medical assistance.

detected

documented.

Check expiry date. Transfusion details not

Check and ensure that patient ID details on blood match that on the wrist band.

Check and ensure that ABO and Rh D group on patient ID and component label

Start transfusion at flow rate instructed.

Observe patients vital signs and general

Recongnise and respond appriopriately to adverse event.

Record outcome of transfusion.

condition

match.

**the patient**

**patient**

patient.

Avoidable harm to

Delayed response to transfusion reaction.

Major morbidity or death due to transfusion event.

**Why things go wrong**

**Why things go wrong**

Adverse reaction not recongnised.

Adverse reaction not responded to appriopriately and urgently.

Unit not tracable. Failure to adhere to SOP.

**Prevention/ precaution**

Errors, events, near misses must be investigated. Outcome of investigation must be used as a learning process to improve procedures.

Computerized support system must be available.

**Prevention/precau-**

responsible for transfusion must be trained on blood adminstration and management of associated adverse events and competency tested

Clinical guidelines must be available and being observed for the management of transfusion-related adverse events.

Adverse reactions are investigated.

**tions**

Patient not monitored Doctors and nurses

### **43. Principle of informed consent in transfusion medicine**

This topic will help transfusion practitioners understand the principles of patient confidentiality and the need for informed consent, understand the policies regarding informed consent for service users, know how to follow standard operational procedures to take and obtain informed consent, understand that it is part of their duty of care as health professional and that they are accountable for the release of information on a client or patient, understand that if patients or client´s record need to be used to help student gain the knowledge and skills which they require or for research purposes, the same principle of informed consent applies. Transfusion practitioners must be able to:


and will not be released to unauthorised persons without their permission (consent).

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 281

6. The organization that employs the health professions who make records are the legal owners of the records, but this does not give anyone in the organization the legal right to access or release this information to a third

7. If patients or clients record need to be used to help student gain the knowledge and skills which they require, the same principle of informed consent applies. The person providing the training will be responsible for making sure the student understand the need for confidentiality and informed consent and the need to follow local procedures for handling and storing of

8. Informed consent includes being informed and giving consent. These two are closely related elements. Being informed requires offering information to potential human subjects. In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. Information provided by researcher should be simple and clear enough for the potential subject to understand and it is the duty of researcher to answer their questions. The subject should also be informed of the right to abstain from participation in the study or withdraw consent to participate at any time without reprisal. The principle of informed consent, aimed at the lawfulness of health assistance, tends to reflect the concept of autonomy and of decisional auto determination of the person requiring and requesting medical and/or surgical interventions. It is the right and responsibility of every competent individual to advance his or her own welfare. This right and responsibility is exercised by freely and voluntarily consenting or refusing consent to recommended medical procedures, based on a sufficient knowledge of the benefits, burdens, and risks involved. The ability to give informed consent depends on;adequate disclosure of information, patient freedom of choice, patient comprehension of information given and patient capacity for decision-making.

9. Three necessary conditions that must be satisfied in obtaining informed consent are;that the individual's decision is voluntary, that this decision is made with an appropriate understanding of the circumstances, that the patient's choice is deliberate insofar as the patient has carefully considered all of the expected benefits, burdens, risk and reasonable alternatives, legally, adequate disclosure includes information concerning the following;diagnosis, nature and purpose of treatment, risks of treatment

and treatment alternatives.

party without the consent of the client.

records.

7. Appreciate the fact that informed consent has legal, ethical, and clinical dimensions.

**What is informed consent?** A process of obtaining a patient's permission before disclosing specific information on the patient. A process of obtaining a patient's permission for a procedure after the patient and doctor have discussed the risks, benefits, and alternatives of the procedure and the patient understands them. A process by which a patient/client confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate voluntarily in an experiment after understanding the risks involved.

**What are the principles of informed consent?** To trust another person with private and personal information about oneself is a significant matter. The patient or client has a right to believe that this information given in confidence will only be used for the purposes for which it was intended and will not be released to others without their permission (consent). It is impractical to obtain the consent of a patient every time you need to share information with other health professionals or staff involved in the health care of the patient or client. What is important is that the patient understands that some information may be made available to others involved in the delivery of their care. We need to obtain the explicit consent of a patient or client before we disclose specific information and it is important that the client or patient can make an informed consent as to whether the information should be disclosed.

### **How can disclosure of patient information occur?**


6. The organization that employs the health professions who make records are the legal owners of the records, but this does not give anyone in the organization the legal right to access or release this information to a third party without the consent of the client.

280 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

sion (consent).

dimensions.

ment after understanding the risks involved.

 **How can disclosure of patient information occur?**

the law or by the order of a court.

interest of the public must be justified.

public interest.

at serious risk.

and will not be released to unauthorised persons without their permis-

7. Appreciate the fact that informed consent has legal, ethical, and clinical

**What is informed consent?** A process of obtaining a patient's permission before disclosing specific information on the patient. A process of obtaining a patient's permission for a procedure after the patient and doctor have discussed the risks, benefits, and alternatives of the procedure and the patient understands them. A process by which a patient/client confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate voluntarily in an experi-

**What are the principles of informed consent?** To trust another person with private and personal information about oneself is a significant matter. The patient or client has a right to believe that this information given in confidence will only be used for the purposes for which it was intended and will not be released to others without their permission (consent). It is impractical to obtain the consent of a patient every time you need to share information with other health professionals or staff involved in the health care of the patient or client. What is important is that the patient understands that some information may be made available to others involved in the delivery of their care. We need to obtain the explicit consent of a patient or client before we disclose specific information and it is important that the client or patient

can make an informed consent as to whether the information should be disclosed.

2. Without the consent of the patient or client when disclosure is required by

3. Without the consent of the patient when the disclosure is in the interest of

4. The public interest means the interest of an individual, or groups of individuals or of society as a whole and would cover issues such as; serious crime, child abuse, drug trafficking or other activities which places others

5. It is our responsibility as health professional (part of our duty of care) and we are accountable for the release of information on a client or patient. The deliberate release of patient information without their consent even in the

1. With the consent (written or verbal) of a client or patient.


### **Questions and answers on the principle of informed consent**

Question 1: Mrs Ford came to the laboratory to have her blood taken for HIV screening. Later that morning her husband Mr Ford who is on warfarin also attends the clinic to have his blood taken for INR investigation. He enquires about whether his wife had attended clinic that morning and what the report of her HIV test was. How will you Handel this situation?

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 283

Answer 5: It is against the principles of patient confidentiality and informed consent to give confidential information on a patient or client to a third party without the consent of the patient. By giving such information without the consent of the wife, the husband will know that

I give consent for myself / child to be a participant in this study. I have been fully informed what participation will involve and had all my questions answered. I understand that I can

I also give consent for my personal data to be used by the research workers in any way they

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from either the bone marrow (BMT) or peripheral blood stem cells. In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone, the technique is referred to as a bone marrow harvest and is performed under general anesthesia and Stored heparinized and the mononuclear cell count of 2-4 x 106 nucleated cells/kg is indicated). In peripheral blood stem cells transplant, the stem cells are collected using cell separator equipment. Mononuclear cells are collected (aphaeresis) after centrifugation before returning the red cells back into the patient. Stem cell content of PBSC is low and collection may be insufficient for transplantation. Prior chemotherapy (cyclophosphamide) and collection during the recovery phase. The peripheral stem cell yield is boosted a 100 times

withdraw from this study at any time without giving reason and without penalty.

I also give consent for recordings to be made relating to my participation.

This study is approved by the hospital Research Ethics Committee

he is most likely not the putative father of the child.

Name………………………………………………………………

Address………………………………..…………………………

**Example of an informed consent form** 

wish and passed to anyone they wish.

Signed…………………………………

**44. Stem cell transplantation**

Participant Consent Form

Study Title:

Date......................

Participant

Answer 1: We need to obtain the explicit consent from a patient or client before we disclose specific information and it is important that the client or patient can make an informed consent as to whether the information should be disclosed.

Question 2: A staff nurse in Eye clinic that has no duty of care for a patient refereed from STD clinic has called the laboratory to enquire about the urine microscopy, culture and sensitivity result of her ex –partner who is suspected to have a sexually transmitted infection. How will you handle this enquiry?

Answer 2: The organization that employs the health professions who make records are the legal owners of the records, but this does not give anyone in the organization the legal right to access or release this information to a third party without the consent of the client particularly when the information accessed is not for the purpose of patient care.

Question 3: Mrs James goes to her family GP in Bolton to submit her early morning urine for pregnancy test. Later that afternoon a GP based in Wigan who has no duty of care to the patient but who introduces himself as a GP and partner of Mrs A rings to enquire about her pregnancy test result. How will you deal with such situation?

Answer 3: It is against the principles of patient confidentiality and informed consent to give confidential information on a patient to a relative clinician or healthcare worker who has no duty of care whatsoever to the patient and does not require the information for the management of the patient.

Question 4: Your brother's partner has just returned from holidays in the Caribbean. She presented to her GP with an episode of vomiting and abdominal pain. Her GP promptly referred her to the laboratory for pregnancy test. Your brother knowing you work in the laboratory in Port Harcourt Teaching Hospital rings you to enquire about his partner's laboratory results. How will you deal with this situation?

Answer 4: As healthcare workers, we are ethical bound not to disclose confidential information on patients or clients to third parties without their consent.

Question 5: A man has just been told that his son's blood group is O positive by his GP. The man however knows that his own blood group is AB positive and that his wife's blood group is O positive. He has read from the internet that a blood group AB parent cannot give birth to an O child. He rings you in the Laboratory to confirm the wife's blood group and enquire about the possibility of the child being his. How will you deal with this issue?

Answer 5: It is against the principles of patient confidentiality and informed consent to give confidential information on a patient or client to a third party without the consent of the patient. By giving such information without the consent of the wife, the husband will know that he is most likely not the putative father of the child.

### **Example of an informed consent form**

Participant Consent Form

Study Title:

282 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

sent as to whether the information should be disclosed.

when the information accessed is not for the purpose of patient care.

pregnancy test result. How will you deal with such situation?

tion on patients or clients to third parties without their consent.

you handle this enquiry?

ment of the patient.

How will you deal with this situation?

**Questions and answers on the principle of informed consent**

Question 1: Mrs Ford came to the laboratory to have her blood taken for HIV screening. Later that morning her husband Mr Ford who is on warfarin also attends the clinic to have his blood taken for INR investigation. He enquires about whether his wife had attended clinic that morning and what the report of her HIV test was. How will you Handel this situation?

Answer 1: We need to obtain the explicit consent from a patient or client before we disclose specific information and it is important that the client or patient can make an informed con-

Question 2: A staff nurse in Eye clinic that has no duty of care for a patient refereed from STD clinic has called the laboratory to enquire about the urine microscopy, culture and sensitivity result of her ex –partner who is suspected to have a sexually transmitted infection. How will

Answer 2: The organization that employs the health professions who make records are the legal owners of the records, but this does not give anyone in the organization the legal right to access or release this information to a third party without the consent of the client particularly

Question 3: Mrs James goes to her family GP in Bolton to submit her early morning urine for pregnancy test. Later that afternoon a GP based in Wigan who has no duty of care to the patient but who introduces himself as a GP and partner of Mrs A rings to enquire about her

Answer 3: It is against the principles of patient confidentiality and informed consent to give confidential information on a patient to a relative clinician or healthcare worker who has no duty of care whatsoever to the patient and does not require the information for the manage-

Question 4: Your brother's partner has just returned from holidays in the Caribbean. She presented to her GP with an episode of vomiting and abdominal pain. Her GP promptly referred her to the laboratory for pregnancy test. Your brother knowing you work in the laboratory in Port Harcourt Teaching Hospital rings you to enquire about his partner's laboratory results.

Answer 4: As healthcare workers, we are ethical bound not to disclose confidential informa-

Question 5: A man has just been told that his son's blood group is O positive by his GP. The man however knows that his own blood group is AB positive and that his wife's blood group is O positive. He has read from the internet that a blood group AB parent cannot give birth to an O child. He rings you in the Laboratory to confirm the wife's blood group and enquire

about the possibility of the child being his. How will you deal with this issue?

Name………………………………………………………………

Address………………………………..…………………………

I give consent for myself / child to be a participant in this study. I have been fully informed what participation will involve and had all my questions answered. I understand that I can withdraw from this study at any time without giving reason and without penalty.

I also give consent for recordings to be made relating to my participation.

I also give consent for my personal data to be used by the research workers in any way they wish and passed to anyone they wish.

Date...................... Signed………………………………… Participant

This study is approved by the hospital Research Ethics Committee

### **44. Stem cell transplantation**

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from either the bone marrow (BMT) or peripheral blood stem cells. In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone, the technique is referred to as a bone marrow harvest and is performed under general anesthesia and Stored heparinized and the mononuclear cell count of 2-4 x 106 nucleated cells/kg is indicated). In peripheral blood stem cells transplant, the stem cells are collected using cell separator equipment. Mononuclear cells are collected (aphaeresis) after centrifugation before returning the red cells back into the patient. Stem cell content of PBSC is low and collection may be insufficient for transplantation. Prior chemotherapy (cyclophosphamide) and collection during the recovery phase. The peripheral stem cell yield is boosted a 100 times

with daily subcutaneous injections of Granulocyte-colony stimulating factor, as well as treatment growth factor (at a dose of 10µg/kg/day for 4-6 days). GCFU help to mobilize stem cells from the donor's bone marrow into the peripheral circulation. Optimum yield with CD34+ cells of >2.5 X 106/kg and granulocyte-macrophage colony forming unit (CFU-GM) of 1-5 x 105/kg is considered optimal for transplantation. Other sources of stem cells include amniotic fluid and umblical cord blood. It is also possible to extract hematopoietic stem cells from amniotic fluid for both autologous and heterogonous use at the time of childbirth. Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However, the small quantity of blood obtained from an umbilical cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 285

4. Children or adults with aplastic anemia who have lost their stem cells

5. Inherited disorders such as sickle-cell disease, thalassaemia, immune de-

7. Neuroblastoma (Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy. It is a neuroendocrine tumor, arising from any neural crest element of the sympathetic nervous system or SNS. It most frequently originates in one of the adrenal glands, but can also develop in nerve tissues in the neck, chest,

8. Ewing's Sarcoma (A malignant round-cell tumour. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the

9. Amyloidosis (A conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. There are numerous symptoms that are associated with this disease. The most common ones have to do with the heart, such as heart failure, arrhythmia, and an irregular heartbeat. Also the respiratory tract can be affected and cause hemoptysis. Usually the spleen enlarges and sometimes ruptures. The gastrointestinal tract is usually affected and causes vomiting, hemorrhaging and diarrhea. The amyloidosis can also affect the motor functions and cause polyneuropathy. When the amyloid fibrils and oligomers get to the skin they can cause skin lesions and petechiae. One of the most famous symptoms is

10. Acquired severe marrow diseases (paroxysmal nocturnal haemoglobinu-

**Autologous.** In autologous HSCT patient is given a high dose of chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow function to

after birth including Fanconi's anaemia.

ficiencies, inborn errors of metabolism.

6. Severe autoimmune disorders.

abdomen, or pelvis).

ribs and clavicle.

macroglossia.

13. Hodgkin's disease.

**Graft types**

ria, red cell aplasia and myelofibrosis).

11. Desmoplastic small round cell tumor.

12. Chronic granulomatous disease.

### **History of stem cell transplant**

Georges Mathé, a French oncologist, performed the first bone marrow transplant in 1959 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a Criticality accident at the Vinča Nuclear Institute, but all of these transplants were rejected. Mathé later pioneered the use of bone marrow transplants in the treatment of leukemia. Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by Donnall Thomas. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968. Hematopoietic stem cell transplantation remains a risky procedure with many possible complications. It has traditionally been reserved for patients with life-threatening diseases. While it remains a procedure involving a high degree of risk, one must keep in mind that many disorders (mainly acute leukemias and neoplastic lymphoproliferative disorders) treated by this procedure. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain cancers. It involves; elimination of a patient immune system using chemotherapy and or radiotherapy and replacement with patient stem cells previously harvested prior to chemotherapy or radiotherapy (autologous) or stem cells from another donor (allogeneic) or from an HLA -matched identical twin (syngeneic). Haemopoietic stem cells are indiated in the following disease conditions.


284 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

**History of stem cell transplant**

with daily subcutaneous injections of Granulocyte-colony stimulating factor, as well as treatment growth factor (at a dose of 10µg/kg/day for 4-6 days). GCFU help to mobilize stem cells from the donor's bone marrow into the peripheral circulation. Optimum yield with CD34+ cells of >2.5 X 106/kg and granulocyte-macrophage colony forming unit (CFU-GM) of 1-5 x 105/kg is considered optimal for transplantation. Other sources of stem cells include amniotic fluid and umblical cord blood. It is also possible to extract hematopoietic stem cells from amniotic fluid for both autologous and heterogonous use at the time of childbirth. Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However, the small quantity of blood obtained from an umbilical cord (typically about 50 mL)

Georges Mathé, a French oncologist, performed the first bone marrow transplant in 1959 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a Criticality accident at the Vinča Nuclear Institute, but all of these transplants were rejected. Mathé later pioneered the use of bone marrow transplants in the treatment of leukemia. Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by Donnall Thomas. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968. Hematopoietic stem cell transplantation remains a risky procedure with many possible complications. It has traditionally been reserved for patients with life-threatening diseases. While it remains a procedure involving a high degree of risk, one must keep in mind that many disorders (mainly acute leukemias and neoplastic lymphoproliferative disorders) treated by this procedure. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain cancers. It involves; elimination of a patient immune system using chemotherapy and or radiotherapy and replacement with patient stem cells previously harvested prior to chemotherapy or radiotherapy (autologous) or stem cells from another donor (allogeneic) or from an HLA -matched identical twin (syngeneic).

makes it more suitable for transplantation into small children than into adults.

Haemopoietic stem cells are indiated in the following disease conditions.

myeloma and lymphoma.

cells.

1. Non malignant disorders such as myelodysplastic syndrome, multiple

2. Pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem

3. Leukemia (ALL, AML, CML and CLL) patients who would not benefit from prolonged treatment with or are already resistant to chemotherapy.


#### **Graft types**

**Autologous.** In autologous HSCT patient is given a high dose of chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow function to

grow new blood cells). Stem cells are extracted (aphaeresis) from the patient and stored frozen. The patient's own stored stem cells are then returned to his/her body, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have several advantages over alogenic transplant; lower risk of infection during the immunecompromised portion of the treatment, the recovery of immune function is rapid, the incidence of patients experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual, graft versus host disease (GVHD) is not a challenge and the procedure-related mortality is low (<5%). These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma. A limitation of this procedure is the risk of tumour cells contaminating the stem cell harvest.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 287

**Allogeneic or syngeneic Autologous**

Chronic myeloid leukaemia Severe autoimmune disorders

cell disease) Multiple myeloma

and mesenchymal system such as osteopetrosis. Hodgkins and non-Hodgkins lymphoma

**Storage of HSC.** HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. Bone marrow cells can be frozen (cryopreserved) for prolonged periods, without damaging too many cells. In the case of allogeneic transplants, fresh HSC are preferred, in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC, a preservative called Dimethyl sulfoxide (DMSO) (DMSO has been used as a cryoprotectant and is still an important constituent of cryoprotectant vitrification mixtures used to preserve organs, tissues, and cell suspensions. Without it, up to 90% of frozen cells will become inactive. In a controlled-rate freezer DMSO prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a

**Stem cell processing.** After harvesting of HSC, it is processed (red cells are removed, the mononuclear cells are concentrated, autologous collections are purged by chemotherapy or antibody treatment to remove residual malignant cells and T-cells to reduce incidence of

**Conditioning.** Prior to infusing stem cells into a patient, conditioning (chemotherapy and total body irradiation (TBI) is carried out. The aim of this is to; eradicate patient's haemopoietic and immune system, eradicate residual malignancy and to suppresses in case of allogeneic stem cell transplant the host immune system to prevent rejection of transplanted foreign stem cells.

**Myeloablative transplants and non-myeloablative transplants.** The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning or preparative regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of

anaemia Acute and chronic leukaemia

Acute lymphoblastic and myeloid leukaemia Amyloidosis

Severe aplastic anaemia including Fanconi, s

Haemoglobinopathies (thalasaemia and sickle

Inborn errors of metabolism in the haemopoietic

Acquired marrow syndrome (aplastic anaemia, myelofibrosis, paroxysmal nocturnal haemoglobinuria) Malignant disorders (myelodysplasia, multiple myeloma, chronic lymphocytic leukaemia and lymphoma)

cryofreezer, which typically utilizes liquid nitrogen.

Stem cell transplant indications

GVHD).

**Allogeneic.** Allogeneic HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin. Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. Transplanting healthy stem cells to the recipient's immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved. The short arm of chromosome 6 contains a cluster of genes known as the Major Histocompatibility Complex (MHC) or the HLA region. These genes encode the HLA antigens and molecules like complement components, tumuor necrosis factor (TNF) and antigens related to antigen processing. A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (type I and type II). In general, mismatches of the type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection and are present in CD8+ cells. HLA-type 11 is present in CD4+ T-cells. A mismatch of an HLA type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical. HLA typing is carried out either by serological technique using antibodies that are specific for individual HLA alleles or by molecular testing using PCR sequence-specific primers. The advantage of this procedure is associated graft versus leukemia (GVL). Mortality from allogeneic stem cell transplantation is higher for the following reasons; immunological incompatibility between donors and recipients despite HLA matching and immunological incompatibility related immunodeficiency, GVHD and graft failure.


Stem cell transplant indications

286 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

related immunodeficiency, GVHD and graft failure.

grow new blood cells). Stem cells are extracted (aphaeresis) from the patient and stored frozen. The patient's own stored stem cells are then returned to his/her body, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have several advantages over alogenic transplant; lower risk of infection during the immunecompromised portion of the treatment, the recovery of immune function is rapid, the incidence of patients experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual, graft versus host disease (GVHD) is not a challenge and the procedure-related mortality is low (<5%). These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma. A limitation of

**Allogeneic.** Allogeneic HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin. Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. Transplanting healthy stem cells to the recipient's immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved. The short arm of chromosome 6 contains a cluster of genes known as the Major Histocompatibility Complex (MHC) or the HLA region. These genes encode the HLA antigens and molecules like complement components, tumuor necrosis factor (TNF) and antigens related to antigen processing. A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (type I and type II). In general, mismatches of the type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection and are present in CD8+ cells. HLA-type 11 is present in CD4+ T-cells. A mismatch of an HLA type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical. HLA typing is carried out either by serological technique using antibodies that are specific for individual HLA alleles or by molecular testing using PCR sequence-specific primers. The advantage of this procedure is associated graft versus leukemia (GVL). Mortality from allogeneic stem cell transplantation is higher for the following reasons; immunological incompatibility between donors and recipients despite HLA matching and immunological incompatibility -

this procedure is the risk of tumour cells contaminating the stem cell harvest.

**Storage of HSC.** HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. Bone marrow cells can be frozen (cryopreserved) for prolonged periods, without damaging too many cells. In the case of allogeneic transplants, fresh HSC are preferred, in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC, a preservative called Dimethyl sulfoxide (DMSO) (DMSO has been used as a cryoprotectant and is still an important constituent of cryoprotectant vitrification mixtures used to preserve organs, tissues, and cell suspensions. Without it, up to 90% of frozen cells will become inactive. In a controlled-rate freezer DMSO prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer, which typically utilizes liquid nitrogen.

**Stem cell processing.** After harvesting of HSC, it is processed (red cells are removed, the mononuclear cells are concentrated, autologous collections are purged by chemotherapy or antibody treatment to remove residual malignant cells and T-cells to reduce incidence of GVHD).

**Conditioning.** Prior to infusing stem cells into a patient, conditioning (chemotherapy and total body irradiation (TBI) is carried out. The aim of this is to; eradicate patient's haemopoietic and immune system, eradicate residual malignancy and to suppresses in case of allogeneic stem cell transplant the host immune system to prevent rejection of transplanted foreign stem cells.

**Myeloablative transplants and non-myeloablative transplants.** The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning or preparative regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSC and to suppress immune reactions. In recent years there has been a shift from the use of myeloablative to non-myeloablative conditioning regimens. Unlike myeloablative regimens, non –myeloablative agents do not completely ablate (destroy) the patient's bone marrow. TBI is used in patient with malignant disease. Drugs used include; cyclophoaphamide, bulsulphan, cytosine, arabinoside and etoposide or nitrosoureas. Stem cells are not transplanted immediately after TBI. It is preferable to allow for a period of 36hours post TBI to allow for the removal of residual chemotherapeutic agent from the patients circulation.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 289

**Complications.** HSCT is associated with a high treatment-related mortality and morbidity in the recipient (10% or higher), which limits its use to conditions that are themselves life-threatening. Major complications are: graft-versus-host disease, infection, veno-occlusive disease,

**Graft-versus-host disease.** Graft-versus-host disease (GVHD) is an inflammatory disease caused by donor –derived immune cells (T lymphocytes) that react against recipient cells. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. Incidence is higher with increasing age of donor and recipient and in cases where there is HLA mismatch between donor and recipient. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. Prophylaxis against GVHD usually involves use of ciclosporin (oral or intravenous) and methotrexate given to remove T cells from donor stem cell infusion. There are two types

**Acute graft-versus-host disease.** Typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver, and is often fatal. Skin rash typically affects the face, palms, soles, ears and sometimes the whole body. Diagnosis is usually by skin biopsy (cell necrosis in the basal layer of epidermis and lymphocyte infiltration). Diarrhoea and associated electrolyte depletion and imbalance may occur. Bilirubin and alkaline phosphatase are elevated although other hepatic enzymes may be normal. Treatment is usually by the use of high-dose corticosteroids such as prednisone. This immuno-suppressive treatment often

**Chronic graft-versus-host disease.** Chronic graft-versus-host disease may also develop after 100 days following allogeneic transplant and it is the major source of late treatment-related complications. Chronic graft-versus-host disease may involve the joints, oral mucose, lacrimal glands and other serosal surfaces and often lead to the development of fibrosis, or scar tissue, similar to scleroderma. Sjogen's syndrome andlichen planus may develop. The immune system is impaired resulting in hyposlenism. Malabsorption and pulmonary abnormalities are common. Management often include use of drugs such as ciclosporin, azathioprine, myco-

**Infection.** Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed (myeloablation). Prior to engraftment patients may go for several weeks without appreciable numbers of white blood cells to help fight infection (Bacterial and fungal infection are frequent). This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in sero-positive patients. Use of oral antibiotics and sometimes intravenous broad-spectrum antibiotics may be commenced after blood cultures and other microbiological samples have been collected to prevent bacterial infection. Oral penicillin can be given prophylactically to reduce effects of gram negative encapsulated organisms affecting the respiratory tract. Antifungal agents such as amphotericin B and caspofungin or voriconazole, fluconazole and

mucositis, infections (sepsis), graft failureand the development of new malignancies.

of GVHD ( Acute and chronic).

leads to deadly infections.

phenolate, mofetil, thalidomide and corticosteriods.

**Myeloablative transplants.** The bone marrow can be ablated with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of myeloablative options are available include cyclophosphamide with busulfan and total body irradiation is commonly employed. This treatment also has an immunosuppressive effect which prevents rejection of the HSC by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease which may be life-threatening; however in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.

**Non-myeloablative allogeneic transplants.** This is a newer treatment approach using lower doses of chemotherapy and radiation which are too low to eradicate all of the bone marrow cells of a recipient. Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse. Also it requires high doses of immunosuppressive agents in the early stages of treatment; these doses are less than for conventional transplants. This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space. Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. This effect is often accompanied by mild graft-versus-host disease. Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and morbidity and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. Examples of non-myeloablative regimens include; fludarabine, low dose irradiation, anti-lymphocyte globulin, low dose Busulfan and cyclophosphamide.

**Engraftment.** Engraftment is usually quicker with PBSC compared to BMT. Cytopenia typically occur within the first 1-3 weeks post transplant. First signs of successful engraftment include; increase in the monocyte and neutrophils followed by platelet coun, there is reticulosis, appearance of natural killer cells (NK) which are the earliest donor-derived lymphocytes to appear. G-CSF can be used to reduce the period of neutropenia, marrow cellularity gradually returns to normal but bone marrow reserve remains impaired for 1-2 years. Profound immunodeficiency persists for 3-12 months and is usually associated with low CD4 helper cells, high CD8 count and high CD8:CD4 for 6 months, after several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system, the offspring of donor-derived hematopoietic stem cells then populate many different organs of the recipient, including the heart, liver, and muscle and help in regenerating injured tissue in these organs and patient blood group changes to that of the donor and the antigen specific immunity becomes that of the donor in about 60 days.

**Complications.** HSCT is associated with a high treatment-related mortality and morbidity in the recipient (10% or higher), which limits its use to conditions that are themselves life-threatening. Major complications are: graft-versus-host disease, infection, veno-occlusive disease, mucositis, infections (sepsis), graft failureand the development of new malignancies.

288 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

HSC and to suppress immune reactions. In recent years there has been a shift from the use of myeloablative to non-myeloablative conditioning regimens. Unlike myeloablative regimens, non –myeloablative agents do not completely ablate (destroy) the patient's bone marrow. TBI is used in patient with malignant disease. Drugs used include; cyclophoaphamide, bulsulphan, cytosine, arabinoside and etoposide or nitrosoureas. Stem cells are not transplanted immediately after TBI. It is preferable to allow for a period of 36hours post TBI to allow for

**Myeloablative transplants.** The bone marrow can be ablated with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of myeloablative options are available include cyclophosphamide with busulfan and total body irradiation is commonly employed. This treatment also has an immunosuppressive effect which prevents rejection of the HSC by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease which may be life-threatening; however in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.

**Non-myeloablative allogeneic transplants.** This is a newer treatment approach using lower doses of chemotherapy and radiation which are too low to eradicate all of the bone marrow cells of a recipient. Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse. Also it requires high doses of immunosuppressive agents in the early stages of treatment; these doses are less than for conventional transplants. This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space. Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. This effect is often accompanied by mild graft-versus-host disease. Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and morbidity and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. Examples of non-myeloablative regimens include; fludarabine, low dose irradiation, anti-lymphocyte globulin, low dose Busulfan and cyclophosphamide.

**Engraftment.** Engraftment is usually quicker with PBSC compared to BMT. Cytopenia typically occur within the first 1-3 weeks post transplant. First signs of successful engraftment include; increase in the monocyte and neutrophils followed by platelet coun, there is reticulosis, appearance of natural killer cells (NK) which are the earliest donor-derived lymphocytes to appear. G-CSF can be used to reduce the period of neutropenia, marrow cellularity gradually returns to normal but bone marrow reserve remains impaired for 1-2 years. Profound immunodeficiency persists for 3-12 months and is usually associated with low CD4 helper cells, high CD8 count and high CD8:CD4 for 6 months, after several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system, the offspring of donor-derived hematopoietic stem cells then populate many different organs of the recipient, including the heart, liver, and muscle and help in regenerating injured tissue in these organs and patient blood group changes to that of the donor and the

antigen specific immunity becomes that of the donor in about 60 days.

the removal of residual chemotherapeutic agent from the patients circulation.

**Graft-versus-host disease.** Graft-versus-host disease (GVHD) is an inflammatory disease caused by donor –derived immune cells (T lymphocytes) that react against recipient cells. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. Incidence is higher with increasing age of donor and recipient and in cases where there is HLA mismatch between donor and recipient. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. Prophylaxis against GVHD usually involves use of ciclosporin (oral or intravenous) and methotrexate given to remove T cells from donor stem cell infusion. There are two types of GVHD ( Acute and chronic).

**Acute graft-versus-host disease.** Typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver, and is often fatal. Skin rash typically affects the face, palms, soles, ears and sometimes the whole body. Diagnosis is usually by skin biopsy (cell necrosis in the basal layer of epidermis and lymphocyte infiltration). Diarrhoea and associated electrolyte depletion and imbalance may occur. Bilirubin and alkaline phosphatase are elevated although other hepatic enzymes may be normal. Treatment is usually by the use of high-dose corticosteroids such as prednisone. This immuno-suppressive treatment often leads to deadly infections.

**Chronic graft-versus-host disease.** Chronic graft-versus-host disease may also develop after 100 days following allogeneic transplant and it is the major source of late treatment-related complications. Chronic graft-versus-host disease may involve the joints, oral mucose, lacrimal glands and other serosal surfaces and often lead to the development of fibrosis, or scar tissue, similar to scleroderma. Sjogen's syndrome andlichen planus may develop. The immune system is impaired resulting in hyposlenism. Malabsorption and pulmonary abnormalities are common. Management often include use of drugs such as ciclosporin, azathioprine, mycophenolate, mofetil, thalidomide and corticosteriods.

**Infection.** Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed (myeloablation). Prior to engraftment patients may go for several weeks without appreciable numbers of white blood cells to help fight infection (Bacterial and fungal infection are frequent). This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in sero-positive patients. Use of oral antibiotics and sometimes intravenous broad-spectrum antibiotics may be commenced after blood cultures and other microbiological samples have been collected to prevent bacterial infection. Oral penicillin can be given prophylactically to reduce effects of gram negative encapsulated organisms affecting the respiratory tract. Antifungal agents such as amphotericin B and caspofungin or voriconazole, fluconazole and

itraconazole may be used to prevent fungal infections such as Candida and Aspergillus species. The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of viral infections particularly herpes simplex, cytomegalovirus (CMV), varicella zoster virus (VZV). CMV is a major threat and is usually associated with potentially fatal pneumonitis, hepatitis, falling blood counts. Recipients who are CMV negative or whose CMV status is unknown must receive CMV negative donor stem cells and blood products. Immunosuppressive drugs are given for a minimum of 6-months after transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications. Pneumocystis carinii pneumonitis may occur and can be prevented by prophylactic co-trimoxazole. Aciclovir may be a useful prophylaxis for varicella zoster virus infection. Epstein-Barr virus (EBV) and associated lympho-proliferative disease are rare. Haemorrhagic cystitis caused by the cyclophosphamide metabolite acrolein or adenovirus or polyomavirus can cause this complication. Mensa can help prevent this complication.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 291

1. Oral carcinoma. Patients after HSCT are at a higher risk for oral carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.

2. Haemolysis and microangiopathic haemolytic anaemia because of ABO

3. Relapse of original or residual disease for example acute and chronic leu-

4. Delayed pulmonary complications including restrictive pneomonitis,

5. Endocrine complications including hypothyroidism particularly associ-

6. Autoimmune disorders including myasthenia, rheumatoid arthritis, ane-

7. Secondary malignancies such non-Hodgkin's lymphoma as well as CNS

8. Growth failure associated with low growth hormone levels in children.

**Blood products support following SCT.** Severe pan-cytopenia is often associated with SCT in the first 1-3 weeks. Blood product support may be required in these critical moments. Red cells concentrates are given to treat anemia, platelet concentrate are given to maintain the

**Prognosis of SCT.** Prognosis in HSCT varies widely dependent upon a number of factors; disease type, stage, stems cell source, HLA-matched status (for allogeneic HCST), and conditioning regimen. A transplant offers a chance for cure or long-term remission if; the inherent complications of graft versus host disease does not manifest, an Immuno-suppressive treatment does not produce a negative life threatening effect and if the recipient survives the spectrum of opportunistic infections. In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants. Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror and colleagues using the Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI). The Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI) was developed to identify relevant comorbidities in the allogeneic stem cell transplantation population and to enable risk assessment before allogeneic transplant. Use this calculator to identify comorbidities in the allogeneic stem cell transplantation population and to enable

/L. All blood product giving post transplant **must be** irradiated

blood group incompatibility between donors and recipients.

**Other complications**

kaemia.

platelet count above 10 x 109

bronchiolitis obliterans.

mia and thrombocytopenia.

complications (neuropathies).

(to kill any lymphocytes) and prevent GVHD.

ated with TBI and eye problems (cataracts).

9. Impaired sexual development and infertility.

**Veno-occlusive disease.** Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin (jaundice), hepatomegaly and fluid retention (ascites), weight gain and cardiac failures are clinical hallmarks of this condition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.

**Graft failure. The risk of graft failure can occur in the following circumstances;** patients with aplastic anaemia and in patients in whom T-cell depleted donor stem cells is used for transplant or as a GVHD prophylaxis. T –cell depletion of donor stem cells prevent donor Tcells form overcoming resistance from host.

**Mucositis.** The injury of the mucosal lining of the mouth and throat and is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Treatment is usually with pain medications plus intravenous infusions to prevent dehydration and malnutrition.

**Graft-versus-tumor effect.** Graft-versus-tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft-versus-Host phenomenon. HSCT patients with either acute or in particular chronic graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse. This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants which do not employ the highest immuno-suppressive regimens.

### **Other complications**

290 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

can cause this complication. Mensa can help prevent this complication.

plus intravenous infusions to prevent dehydration and malnutrition.

cells form overcoming resistance from host.

itraconazole may be used to prevent fungal infections such as Candida and Aspergillus species. The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of viral infections particularly herpes simplex, cytomegalovirus (CMV), varicella zoster virus (VZV). CMV is a major threat and is usually associated with potentially fatal pneumonitis, hepatitis, falling blood counts. Recipients who are CMV negative or whose CMV status is unknown must receive CMV negative donor stem cells and blood products. Immunosuppressive drugs are given for a minimum of 6-months after transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications. Pneumocystis carinii pneumonitis may occur and can be prevented by prophylactic co-trimoxazole. Aciclovir may be a useful prophylaxis for varicella zoster virus infection. Epstein-Barr virus (EBV) and associated lympho-proliferative disease are rare. Haemorrhagic cystitis caused by the cyclophosphamide metabolite acrolein or adenovirus or polyomavirus

**Veno-occlusive disease.** Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin (jaundice), hepatomegaly and fluid retention (ascites), weight gain and cardiac failures are clinical hallmarks of this condition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.

**Graft failure. The risk of graft failure can occur in the following circumstances;** patients with aplastic anaemia and in patients in whom T-cell depleted donor stem cells is used for transplant or as a GVHD prophylaxis. T –cell depletion of donor stem cells prevent donor T-

**Mucositis.** The injury of the mucosal lining of the mouth and throat and is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Treatment is usually with pain medications

**Graft-versus-tumor effect.** Graft-versus-tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft-versus-Host phenomenon. HSCT patients with either acute or in particular chronic graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse. This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants which do not employ the highest immuno-suppressive regimens.


**Blood products support following SCT.** Severe pan-cytopenia is often associated with SCT in the first 1-3 weeks. Blood product support may be required in these critical moments. Red cells concentrates are given to treat anemia, platelet concentrate are given to maintain the platelet count above 10 x 109 /L. All blood product giving post transplant **must be** irradiated (to kill any lymphocytes) and prevent GVHD.

**Prognosis of SCT.** Prognosis in HSCT varies widely dependent upon a number of factors; disease type, stage, stems cell source, HLA-matched status (for allogeneic HCST), and conditioning regimen. A transplant offers a chance for cure or long-term remission if; the inherent complications of graft versus host disease does not manifest, an Immuno-suppressive treatment does not produce a negative life threatening effect and if the recipient survives the spectrum of opportunistic infections. In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants. Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror and colleagues using the Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI). The Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI) was developed to identify relevant comorbidities in the allogeneic stem cell transplantation population and to enable risk assessment before allogeneic transplant. Use this calculator to identify comorbidities in the allogeneic stem cell transplantation population and to enable risk assessment before allogeneic transplant using the Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI). The following co-morbidities can to a larger extent determine the success of a transplant.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 293

• Prior solid tumor (excluding non-melanoma skin cancer).

The alkaline denaturation test is a test used for differentiating between foetal and adult blood. It is sometimes necessary to establish the origin of a blood sample (foetal, maternal or adult). The principle of the test is based on the resistance of foetal red cells containing haemoglobin F to alkaline denaturation. Examples of cases where it may be necessary to determine the origin

• In cases of PV bleed in a pregnant mother (particularly Rhesus nega-

• Inadequate or mis-labelling of samples (cord and maternal samples)

• In cases of forensic investigation to determine if blood spot on a

**Sample requirement.** Sample must contain macroscopic unaltered blood free from contamination by faeces and vomit. The sample must be less than 3 days old. Each test is controlled

1. Prepare 0.12N NaOH by diluting 0.3N NaOH by adding 200mls of 0.12N

2. Label the 75x12mm tubes appriopriately and prepare a haemolysate of the test and control samples by adding 2 drops of blood into a tube and

using a cord sample as positive control and an adult sample as a negative control.

• In cases of a blood tap from amniocentesis

crime scene is foetal or adult blood.

1. 2 Plastic coombs tube (75 x 12mm) per test and control

NaOH to 500mls of distilled water.

• Valvular Heart Disease (except mitral valve prolapse).

**45. Alkaline denaturation test**

tive mother)

**Instrumentation /reagents required**

• Pasteur pipettes

• Tube rack

• Centrifuge

• Water

**Method**

• 0.12N NaOH

of a blood sample include:

### **Hepatic disease**


### **Pulmonary disease**


### **Other factors**


### **45. Alkaline denaturation test**

292 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

determine the success of a transplant.

2.5 x ULN).

• None or mild disease

on slight activity).

requiring oxygen).

tricular arrhythmias).

consult or treatment).

• Obesity (body mass index > 35 kg/m2)

• Peptic ulcer (requiring treatment)

dialysis, or prior renal transplant).

**Hepatic disease** 

**Pulmonary disease**

**Other factors**

• None

risk assessment before allogeneic transplant using the Hematopoietic Cell Transplantation-Specific Co-morbidity Index (HCT-CI). The following co-morbidities can to a larger extent

• Mild (chronic hepatitis, bilirubin > Upper Limit of Normal (ULN) to

• Moderate or severe (cirrhosis, bilirubin > 1.5 x ULN, or AST/ALT >

• Moderate pulmonary (DLCO and/or FEV1 66% to 80% or dyspnea

• Severe pulmonary (DLCO and/or FEV1 = 65% or dyspnea at rest or

• Arrhythmia (Atrial fibrillation or flutter, sick sinus syndrome, or ven-

• Cardiac (CAD, CHD, myocardial infarction or ejection fraction = 50%).

• Psychiatric disturbance (depression or anxiety requiring psychiatric

• Infection (requiring continuation of antimicrobial treatment after day 0.

• Rheumatologic (SLE, RA, polymyositis, polymyalgia rheumatica).

• Moderate or severe renal failure (serum Cr > 2 mg/dL or 177 µmol/L,

• Cerebrovascular disease (TIA or cerebrovascular accident).

• Inflammatory bowel disease (Crohn's or ulcerative colitis)

• Inflammatory bowel disease (Crohn's or ulcerative colitis). • Inflammatory bowel disease (Crohn's or ulcerative colitis).

• Diabetes (requiring insulin or oral hypoglycemic)

1.5 x ULN, or AST/ALT > ULN to 2.5 x ULN).

The alkaline denaturation test is a test used for differentiating between foetal and adult blood. It is sometimes necessary to establish the origin of a blood sample (foetal, maternal or adult). The principle of the test is based on the resistance of foetal red cells containing haemoglobin F to alkaline denaturation. Examples of cases where it may be necessary to determine the origin of a blood sample include:


**Sample requirement.** Sample must contain macroscopic unaltered blood free from contamination by faeces and vomit. The sample must be less than 3 days old. Each test is controlled using a cord sample as positive control and an adult sample as a negative control.

#### **Instrumentation /reagents required**

1. 2 Plastic coombs tube (75 x 12mm) per test and control


#### **Method**


filling it with distilled water. Test haemolysate can be prepared from blood samples, blood stained sheets and sanitary pads.

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 295

**INDEX** 

AABB (American Association of Blood Banks) *81, 90,221*

antigens *17, 22-4, 26, 39, 44, 109, 178*

Activated partial thromboplastin time (APTT) *142, 145*-*6*

Agglutination *4*-*12, 26*-*7, 30*-*1, 36, 38, 41*-*2, 79, 92*-*7, 99*-*100, 111, 177, 181, 203*-*7, 215*-*16, 263*

AHG (anti-human globulin) *5, 10*-*11, 92, 109, 113, 171, 174, 182, 195, 203*-*4, 206*-*7, 210, 213, 215*-*16*

Alloantibodies *21, 27, 54, 63, 79, 91*-*3, 98*-*103, 110, 112*-*14, 120, 156*-*7, 176, 194, 196, 216*

Adverse events *130, 142, 220, 222, 252, 265, 268, 274*

reaction *7*-*9, 11, 31, 95, 109, 166, 181*

AIHA (Autoimmune Haemolytic Anaemia) *112, 156, 185, 204, 210*-*12*

reagent *11, 95*-*6, 198, 203, 207* AICC (Anti-Inhibitor Coagulation Complex) *141*-*2*

Alleles *23, 38*-*9, 45*-*6, 48, 165, 167, 172*-*3, 179, 184*-*5, 187*

significant *92*-*3, 98*-*9, 101*-*2, 118, 156, 158*

albumin *76, 133, 142, 158*-*9, 166, 177, 201, 207* Albumin Techniques *93, 96*

Acute normovolaemic haemodilution *71, 75*

Adverse reactions *54, 57, 132, 135, 151, 274*

causing *11, 203, 206* grading *262*-*3* inhibition *41* mixed-field *32, 36*

unexpected *35*

Alkaline denaturation test *289, 295*

antibodies *22-3, 26-7, 31, 44, 166*

barrier *24-6, 37, 54, 98, 149*

incompatibility *24, 95, 287* ABO blood group system *20, 22-3, 26, 43, 45, 102, 162*

anomalies *27*

distribution *38*

ABO blood grouping discrepancies *30* ABO blood grouping reagents *27*

acid citrate -dextrose (ACD) *50* Acid elutions *114, 122*-*4*

Additive solution *51, 62*

ABO genes *38, 44*

ABO *4, 6, 13, 17, 21-3, 28, 40, 44-5, 47-8, 97-8, 146, 157, 192-3, 220-1, 260-2*

**A**


**Result.** Foetal red cells containing haemoglobin F remains pink (resist denaturation) while adult maternal sample containg adult haemoglobin turns brown.

### **INDEX**

### **A**

294 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

remove the stroma

filling it with distilled water. Test haemolysate can be prepared from

3. Place the tubes with the haemolysate in a centrifuge for 60 seconds to

4. Transfer 8 volumes of the haemolysate into a second tube and add 2 volumes of 0.12N NaOH, mix and observe immediately. Compare the colour against the original haemolysate. Include positive 9 known foetal sample)

**Result.** Foetal red cells containing haemoglobin F remains pink (resist denaturation) while

blood samples, blood stained sheets and sanitary pads.

and negative controls (known adult maternal sample).

adult maternal sample containg adult haemoglobin turns brown.

AABB (American Association of Blood Banks) *81, 90,221* ABO *4, 6, 13, 17, 21-3, 28, 40, 44-5, 47-8, 97-8, 146, 157, 192-3, 220-1, 260-2* antibodies *22-3, 26-7, 31, 44, 166* anomalies *27* antigens *17, 22-4, 26, 39, 44, 109, 178* barrier *24-6, 37, 54, 98, 149* distribution *38* incompatibility *24, 95, 287* ABO blood group system *20, 22-3, 26, 43, 45, 102, 162* ABO blood grouping discrepancies *30* ABO blood grouping reagents *27* ABO genes *38, 44* acid citrate -dextrose (ACD) *50* Acid elutions *114, 122*-*4* Activated partial thromboplastin time (APTT) *142, 145*-*6* Acute normovolaemic haemodilution *71, 75* Additive solution *51, 62* Adverse events *130, 142, 220, 222, 252, 265, 268, 274* Adverse reactions *54, 57, 132, 135, 151, 274* Agglutination *4*-*12, 26*-*7, 30*-*1, 36, 38, 41*-*2, 79, 92*-*7, 99*-*100, 111, 177, 181, 203*-*7, 215*-*16, 263* causing *11, 203, 206* grading *262*-*3* inhibition *41* mixed-field *32, 36* reaction *7*-*9, 11, 31, 95, 109, 166, 181* unexpected *35* AHG (anti-human globulin) *5, 10*-*11, 92, 109, 113, 171, 174, 182, 195, 203*-*4, 206*-*7, 210, 213, 215*-*16* reagent *11, 95*-*6, 198, 203, 207* AICC (Anti-Inhibitor Coagulation Complex) *141*-*2* AIHA (Autoimmune Haemolytic Anaemia) *112, 156, 185, 204, 210*-*12* albumin *76, 133, 142, 158*-*9, 166, 177, 201, 207* Albumin Techniques *93, 96* Alkaline denaturation test *289, 295* Alleles *23, 38*-*9, 45*-*6, 48, 165, 167, 172*-*3, 179, 184*-*5, 187* Alloantibodies *21, 27, 54, 63, 79, 91*-*3, 98*-*103, 110, 112*-*14, 120, 156*-*7, 176, 194, 196, 216* significant *92*-*3, 98*-*9, 101*-*2, 118, 156, 158*

alloantibody screening *100*-*2* Allogeneic transplants *282*-*8* Allogenic blood *72, 128*-*9, 131, 133*-*4, 143, 162* Allogenic blood transfusion *100, 129, 131, 162* Alloimmunization *61, 74, 100*-*2, 116, 127, 134, 142, 201* incidence of *101*-*2* Amniocentesis *120*-*2, 127, 173, 289* Amorph blood group genes *46* Anaemia *25, 35, 115, 126*-*7, 129, 131, 134, 152, 162, 170, 212, 283* Anaphylatoxins *73*-*4, 145, 198* ANH (Acute Normovolaemic Haemodilution) *71, 73, 75*-*9* Antagonists *131, 141, 162* Anti *9, 17, 21, 24, 26*-*7, 29, 34, 84, 99, 108, 119*-*20, 171*-*2, 174*-*5, 200, 204* A*1 29, 33*-*4* Hepatitis *160* IgG *202, 204, 213* IH *191*-*2* Inhibitor Coagulant Complex *141*-*2* Kell *184, 186, 201*-*2* Lea *21, 98, 107, 109, 179, 195* RhD immunoglobulin *117* Antibodies *4*-*11, 14*-*27, 33*-*5, 40*-*5, 82*-*6, 92*-*5, 100*-*5, 109*-*10, 172*-*5, 181*-*91, 193*-*6, 199*-*204, 210*-*13, 215*-*16, 260*-*2* cold auto *113* cold reacting *98*-*9* free *41, 181, 204, 210* patientʹs blood stream *204* plasma cells secretes *16* red cell *14* significant *14, 91*-*2, 111*-*12, 174, 186, 190*-*1, 194, 215*-*16* Antibody coating *113*-*14, 199, 203, 207, 213* Antibody eluting *210* Antibody identification *100, 104*-*5, 109, 196, 262* Antibody identification test *100, 104*-*5* Antibody neutralization *41* Antibody panel *92, 109* Antibody panel result *106*-*8* Antibody production *4, 15*-*17, 104, 166* Antibody reaction *5, 8, 27, 177, 261* Antibody screen *33, 83*-*4, 91, 94*-*5, 97*-*8, 103, 115*-*16, 118, 120*-*1, 146, 216, 267, 272* positive *34, 91, 93, 103* Antibody screening *35, 91, 97, 112, 116, 121, 191, 194, 221, 261*-*2* Antibody screening cells *92, 105, 196, 261*

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 297

Anticoagulant *3, 49, 54, 56*-*7, 59, 73, 76*-*7, 87, 133, 144, 217, 286*

Antigen binding sites *4, 19* Antigen group *105, 184* Antigen phenotypes *47*

Antigen presenting cells see APC

Antigen testing of patients *110*

missing *32, 37* offending *103, 173* weak reacting *27* Antiglobulin test *11, 95, 203, 206, 295* antisera *30*-*1, 175*-*7, 261*

APC (antigen presenting cells) *15*-*16* Apheresis *56, 59*-*61, 65, 73, 137*

Artificial oxygen carriers (AOC) *131*-*2* Associated blood group antigens *13*

Antiserum *41*-*2, 216*

Aprotinin *130, 144*

ATP levels *50, 52*-*3*

Auto control *100, 112, 196*

Autocontrol *32*-*4, 38, 207*

Batch products *258*-*60*

Bilirubin *285*-*6, 288*

**B**

warm *113*-*15*

Bacteria *15, 18, 22, 28, 87*-*8, 202*

Blood bag *54, 76, 78, 133, 265*

hospital *88, 97, 242*

Antigen sites *4, 7*-*8, 15, 29, 166, 170*-*1, 177, 197, 199*

Antigenic determinants *4*-*5, 7*-*8, 27, 29*-*30, 166, 187*

high frequency *173, 185, 189, 196*

APTT (activated partial thromboplastin time) *142, 145*-*6*

Audit *147, 152, 219, 222, 232, 237*-*8, 240*-*2, 248, 253, 256*

Autoantibodies *27, 110, 112*-*15, 167, 196, 210, 212*-*13*

inventory control management of *259*-*60*

Blood bank *4, 55, 57, 68*-*9, 83, 97, 132, 134, 176, 213, 220, 230, 260, 267, 270*-*2*

defined blood-group *162* first blood system *187* foreign *102*-*4, 201*

corresponding *8, 22, 35, 92, 94*-*5, 109*-*10*

Antigen-antibody reaction *5*-*6, 31, 193, 197*-*8, 200, 202, 204, 206, 210, 215, 263*

antigens *4*-*8, 13*-*19, 21*-*3, 37*-*40, 42, 46*-*8, 91*-*3, 101*-*5, 109*-*13, 162*-*7, 170*-*8, 180*-*4, 189*-*93,* 


296 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

alloantibody screening *100*-*2* Allogeneic transplants *282*-*8*

Anaphylatoxins *73*-*4, 145, 198*

A*1 29, 33*-*4* Hepatitis *160* IgG *202, 204, 213*

IH *191*-*2*

Kell *184, 186, 201*-*2*

cold auto *113* cold reacting *98*-*9* free *41, 181, 204, 210* patientʹs blood stream *204* plasma cells secretes *16*

red cell *14*

Antibody eluting *210*

Antibody neutralization *41* Antibody panel *92, 109* Antibody panel result *106*-*8*

Antibody coating *113*-*14, 199, 203, 207, 213*

Antibody identification test *100, 104*-*5*

Antibody production *4, 15*-*17, 104, 166* Antibody reaction *5, 8, 27, 177, 261*

positive *34, 91, 93, 103*

Antibody screening cells *92, 105, 196, 261*

Antibody identification *100, 104*-*5, 109, 196, 262*

Antagonists *131, 141, 162*

Allogenic blood *72, 128*-*9, 131, 133*-*4, 143, 162* Allogenic blood transfusion *100, 129, 131, 162*

incidence of *101*-*2* Amniocentesis *120*-*2, 127, 173, 289* Amorph blood group genes *46*

Alloimmunization *61, 74, 100*-*2, 116, 127, 134, 142, 201*

Anaemia *25, 35, 115, 126*-*7, 129, 131, 134, 152, 162, 170, 212, 283*

Anti *9, 17, 21, 24, 26*-*7, 29, 34, 84, 99, 108, 119*-*20, 171*-*2, 174*-*5, 200, 204*

significant *14, 91*-*2, 111*-*12, 174, 186, 190*-*1, 194, 215*-*16*

Antibody screen *33, 83*-*4, 91, 94*-*5, 97*-*8, 103, 115*-*16, 118, 120*-*1, 146, 216, 267, 272*

Antibody screening *35, 91, 97, 112, 116, 121, 191, 194, 221, 261*-*2*

Antibodies *4*-*11, 14*-*27, 33*-*5, 40*-*5, 82*-*6, 92*-*5, 100*-*5, 109*-*10, 172*-*5, 181*-*91, 193*-*6, 199*-*204, 210*-*13, 215*-*16, 260*-*2*

ANH (Acute Normovolaemic Haemodilution) *71, 73, 75*-*9*

Inhibitor Coagulant Complex *141*-*2*

Lea *21, 98, 107, 109, 179, 195* RhD immunoglobulin *117*

	- high frequency *173, 185, 189, 196*
	- missing *32, 37*
	- offending *103, 173*
	- weak reacting *27*
	- antisera *30*-*1, 175*-*7, 261*

### **B**

Bacteria *15, 18, 22, 28, 87*-*8, 202* Batch products *258*-*60* inventory control management of *259*-*60* Bilirubin *285*-*6, 288* Blood bag *54, 76, 78, 133, 265* Blood bank *4, 55, 57, 68*-*9, 83, 97, 132, 134, 176, 213, 220, 230, 260, 267, 270*-*2* hospital *88, 97, 242*

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 299

Complement cascade *197*-*9, 201, 210, 212* Complement-coated red blood cells *209*

Coombs *11, 183, 186, 188, 190*-*1, 208, 210* Coombs serum *204, 206, 210, 213*

Consent *83, 266, 269, 275*-*9*

Cord blood *38, 214, 280* Cord blood cells *113* Cord cells *191*-*2*

CPA standard *259,* 

Complement components *11, 196, 203*-*6, 211, 282*

Continuous quality improvement (CQI) *235*-*6, 258*

CPA (clinical pathology accreditation) *217, 221, 248, 255,* 

Crossmatch *25, 80, 91*-*7, 145, 177, 183, 192*-*3, 196, 262, 271*

Disseminated intravascular coagulation *136, 150, 153*-*4*

Donations *54*-*7, 62, 68*-*9, 74, 5, 82, 90, 136, 155, 220*

EBV (estimated blood volume) *77, 88, 134, 286*

Enzyme technique *5, 10, 174, 180, 207* Enzyme treatment *10, 105, 111, 174, 183, 194*

Documentation *88, 218*-*21, 223, 228, 237, 241, 248*-*9, 253, 255, 268*

Duffy *5*-*6, 20*-*1, 48, 80, 105, 109, 111*-*12, 114, 187, 195, 206, 208, 261*

CPDA (citrate phosphate-dextrose Ad…*, 50*-*1, 53, 65, 77, 87, 154*

Cryoprecipitate *25, 63*-*5, 90, 132*-*3, 136*-*7, 141, 149, 153*-*4, 201, 220, 270*

DAT( direct antiglobulin test) *84, 92, 103*-*5, 112*-*13, 115, 127, 157, 177, 196, 203*-*5, 210, 213*-*14*

CPD (citrate phosphate-dextrose) *50*-*1, 218, 243, 255*

CQI (continuous quality improvement) *235*-*6, 258*

Cromer and Knops blood group antigen *14*

Creutzfeldt-Jacob disease*,* see CJD

Cryoprecipitate unit of *146* Cryoprecipitate poor plasma *63*-*4* Crypreservation of red blood cell *50*

Delayed haemolytic reactions *84*

Diego blood group antigens *14*

Donath-Landsteriner Test *193, 213*

Diego blood group *13*

Duffy antigens *186*-*8* Dyspnoea *85*-*7, 265*

Emergency group *145* Engraftment *36, 284*

**D**

**E**

```
Blood bank reagents 221
Blood bank refrigerators 219, 252
Blood banking 4, 8, 104, 199, 261, 264
Blood banking reagents 260
Blood donations 54, 57-9, 63, 67-9, 71, 82-3, 187, 294
Blood donations
         non-remunerated 66, 68
         remunerated 67
         voluntary non-remune… 67, 70
         programme 70
         recruitment 70
         session 69
Blood donors 24, 54-5, 67-70, 81-3, 90, 100-2, 112, 151, 156, 252
         asymptomatic 156
         commercial remunerate… 71
         family 71
         female 68
         low risk 70
         remunerated 67, 71
         screening of 82
         voluntary 67
         HIV 88
Blood group antigens 4, 13-14, 20, 26, 41, 47, 110-11, 115, 169, 185, 261
Blood transfusion service 67, 230, 243, 245, 247, 253
Blood typing 3, 213
Blood volume 2, 72, 76-7, 135, 142-4, 152
Bombay phenotype 42-3
Bovine Serum Albumin 7, 9-10, 96, 113
```
### **C**

CFC (continuous flow centrifugation) *59* Chimerism *36*-*7* CIP (continuous improving process) *235*-*6* Citrate *50, 72, 87, 202* Citrate Phosphate Dextrose Adenine*, 50*-*1, 87* CJD (Creutzfeldt- Jakob disease) *55, 90* CMV *26, 61, 80, 83, 88, 92, 97*-*8, 134, 138, 156, 158, 270, 272, 286* Colton blood group *13* Complement *18*-*19, 23, 31, 95, 103, 112, 174, 180, 183*-*4, 189*-*90, 192*-*3, 196*-*7, 199*-*204, 206, 210*-*15, 264, 295* Complement fix *18, 113* Complement activation *19*-*20, 23, 189, 197*-*9, 201*-*2* Complement binding *193, 208, 213*

Complement cascade *197*-*9, 201, 210, 212* Complement-coated red blood cells *209* Complement components *11, 196, 203*-*6, 211, 282* Consent *83, 266, 269, 275*-*9* Continuous quality improvement (CQI) *235*-*6, 258* Coombs *11, 183, 186, 188, 190*-*1, 208, 210* Coombs serum *204, 206, 210, 213* Cord blood *38, 214, 280* Cord blood cells *113* Cord cells *191*-*2* CPA (clinical pathology accreditation) *217, 221, 248, 255,*  CPA standard *259,*  CPD (citrate phosphate-dextrose) *50*-*1, 218, 243, 255* CPDA (citrate phosphate-dextrose Ad…*, 50*-*1, 53, 65, 77, 87, 154* CQI (continuous quality improvement) *235*-*6, 258* Creutzfeldt-Jacob disease*,* see CJD Cromer and Knops blood group antigen *14* Crossmatch *25, 80, 91*-*7, 145, 177, 183, 192*-*3, 196, 262, 271* Cryoprecipitate *25, 63*-*5, 90, 132*-*3, 136*-*7, 141, 149, 153*-*4, 201, 220, 270* Cryoprecipitate unit of *146* Cryoprecipitate poor plasma *63*-*4* Crypreservation of red blood cell *50*

### **D**

298 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

Blood donations *54, 57*-*9, 63, 67*-*9, 71, 82*-*3, 187, 294*

voluntary non-remune… *67, 70*

commercial remunerate… *71*

Blood transfusion service *67, 230, 243, 245, 247, 253*

Blood donors *24, 54*-*5, 67*-*70, 81*-*3, 90, 100*-*2, 112, 151, 156, 252*

Blood group antigens *4, 13*-*14, 20, 26, 41, 47, 110*-*11, 115, 169, 185, 261*

non-remunerated *66, 68*

remunerated *67*

programme *70* recruitment *70* session *69*

asymptomatic *156*

remunerated *67, 71* screening of *82* voluntary *67* HIV *88*

Blood volume *2, 72, 76*-*7, 135, 142*-*4, 152*

Bovine Serum Albumin *7, 9*-*10, 96, 113*

CFC (continuous flow centrifugation) *59*

CIP (continuous improving process) *235*-*6*

Citrate Phosphate Dextrose Adenine*, 50*-*1, 87* CJD (Creutzfeldt- Jakob disease) *55, 90*

Complement activation *19*-*20, 23, 189, 197*-*9, 201*-*2*

CMV *26, 61, 80, 83, 88, 92, 97*-*8, 134, 138, 156, 158, 270, 272, 286*

Complement *18*-*19, 23, 31, 95, 103, 112, 174, 180, 183*-*4, 189*-*90, 192*-*3, 196*-*7, 199*-*204, 206, 210*-*15, 264, 295*

family *71* female *68* low risk *70*

Blood typing *3, 213*

Chimerism *36*-*7*

Citrate *50, 72, 87, 202*

Colton blood group *13*

Complement fix *18, 113*

Complement binding *193, 208, 213*

**C**

Bombay phenotype *42*-*3*

Blood bank reagents *221*

Blood banking reagents *260*

Blood donations

Blood bank refrigerators *219, 252* Blood banking *4, 8, 104, 199, 261, 264*

> DAT( direct antiglobulin test) *84, 92, 103*-*5, 112*-*13, 115, 127, 157, 177, 196, 203*-*5, 210, 213*-*14* Delayed haemolytic reactions *84* Diego blood group *13* Diego blood group antigens *14* Disseminated intravascular coagulation *136, 150, 153*-*4* Documentation *88, 218*-*21, 223, 228, 237, 241, 248*-*9, 253, 255, 268* Donath-Landsteriner Test *193, 213* Donations *54*-*7, 62, 68*-*9, 74, 5, 82, 90, 136, 155, 220* Duffy *5*-*6, 20*-*1, 48, 80, 105, 109, 111*-*12, 114, 187, 195, 206, 208, 261* Duffy antigens *186*-*8* Dyspnoea *85*-*7, 265*

### **E**

EBV (estimated blood volume) *77, 88, 134, 286* Emergency group *145* Engraftment *36, 284* Enzyme technique *5, 10, 174, 180, 207* Enzyme treatment *10, 105, 111, 174, 183, 194*

Enzymes *5, 10, 28, 39, 48, 52, 83, 92, 109, 111, 161, 182*-*4, 186, 188*-*9, 193, 197, 200, 207* EOPs (equipment operating procedure) *219, 237* EQA (External Quality Assessment) *221, 233*-*5, 239* EQA schemes *221, 233*-*5, 240* Equipment downtime *248, 257* Equipment operating procedure (EOPs) *219, 237* Errors *26, 30*-*1, 75, 84, 95, 140, 218*-*19, 223, 229, 231*-*2, 254, 257, 269, 271*-*4* prevention of *271*-*5* Erythropoietin *75, 129* Estimated blood volume see EBV External quality assessment *221, 231, 233*-*4, 238, 244, 257* Extravascular hemolysis *199*-*202*

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 301

private *1, 48* silent *2, 46, 173*

Glucose *3, 13, 51, 62*

**H**

Glycosytransferase *2, 23, 39*

Haemolysate *2*/*1, 289*-*90*

Haemphilia *6*/*3, 140*-*2, 160*-*1* HAV (hepatitis A virus) *1, 88*

Hemoglobinuria *2, 201, 212*

History of blood transfusion *2, 2, 294*

HPA (human platelet antigens) *2, 150, 157*

Human Normal Immunoglobulin (HNIG) *1, 226*

HSCT (Hematopoietic stem cell transplant *4*/*3, 279*-*80, 283*-*4* HTR*,* see haemolytic transfusion reacti… *4*/*3, 279*-*80, 285, 287*

IAT (indirect antiglobulin test) *95, 100, 103*-*104, 120, 203, 206, 215*

*199*-*01, 204, 272*

HCV antibody *1, 82*

HLA genes *1, 282*

HSC *4*/*2 279*-*80, 283*-*4*

Hypothermia *84, 87*

**I**

Horizontal audit *2, 222, 237*

*92, 208, 260*-*1*

Genotypes *9*/*8, 29, 40, 45, 48, 165*-*5, 168, 173, 179*

Glycoproteins *8, 10, 13, 15, 40, 144, 178, 182, 188*

Haemoglobinuria *6*/*3, 199*-*201, 212*-*13, 265*

Haemolysin *8*/*6, 24*-*6, 54, 79, 136, 158*

HBV (hepatitis B virus) *4, 83, 88, 218, 225* HCV (hepatitis C virus) *4, 80, 82, 88, 225*

Hemolysis *9*/*7, 31, 84, 92, 192*-*3, 199*-*200, 202, 212* Hemolytic transfusion reactions *4, 24, 166, 182, 190* Hepatitis *12*/*8, 69, 72, 80, 82*-*3, 88*-*9, 140, 225*-*7, 286*

GLP (Good Laboratory Practice) *5, 217, 223, 229, 255, 295*

GMP (Good Manufacturing Practice) *6*/*4, 217*-*18, 221*-*2, 255, 295*

GVHD (graft-versus-host disease) *13*/*10, 60, 74, 80, 134, 138, 154, 270, 272, 282*-*5, 287*

Haemolytic transfusion reactions *12*/*8, 79, 98, 100*-*2, 183*-*4, 191, 200*-*1, 204, 272*

HIV (human immunodeficiency virus) *10*/*9, 45, 92, 110, 127, 168, 172*-*3, 175, 178, 216* HLA (Human leukocyte antigen) *11*/*10, 48, 85*-*6, 98, 135, 150, 155, 157, 190, 280, 282*

Haemolytic transfusion reaction (HTR) *21*/*15, 61, 79, 84, 98, 100*-*2, 162, 180, 183*-*4, 186, 188, 190*-*1, 196,* 

HDN (Hemolytic disease of the Newborn *23*/*13, 43, 92, 104*-*5, 114, 119, 121, 126*-*7, 170, 173, 182*-*5, 188*-

### **F**

Fab portion *10*-*11, 203* Factor IX *10, 160* Factor VIII(FVIII) *137, 140, 160*-*1* Factor XI(FXI) *136, 161* Family replacement donor *71* Fc portion *10*-*11, 198, 203, 206, 211* Fc receptors *17*-*18, 211* Fatal blood cells *115, 189* Fetal cells *122, 216* Fetal haemoglobin *123*-*3* Fetal RBCs *121*-*3* FFP (Fresh frozen Plasma) *24*-*5, 60, 62*-*5, 85, 90, 133, 136*-*7, 141, 145*-*9, 152*-*3, 201, 220, 258, 265, 270* Fibrinogen *35, 61, 65, 131, 136*-*7, 145*-*7, 263* Fibrinogen level *149, 153,*  Fisher Race *163, 167*-*8* Flow cytometry *123*-*4,*  FMH (Feto Maternal Haemorrhage) *17, 101*-*2, 118, 120*-*3, 125*-*6, 128, 142, 243, 262* Foetal cells *103, 124*-*5* Fresh frozen plasma *24*-*5, 60, 62*-*5, 90, 133, 136*-*7, 141, 148, 152, 201, 258* Frozen plasma *62*-*3, 158* Frozen Plasma (FP) *24*-*5, 60, 62*-*5, 90, 133, 136*-*7, 141, 148, 152, 158, 201, 258* Fya *10, 20*-*1, 47, 80, 98, 104*-*8, 111*-*12, 114, 174, 187, 206, 262* Fya and fyb antigens *187*-*8* Fyb *10, 20*-*1, 45, 80, 98*-*9, 105*-*8, 111*-*12, 114, 174, 187, 206,* 

### **G**

Gamma/X-irradiated red cells *1 155* Genes *20*/*14, 29, 39*-*40, 44*-*6, 48, 137, 167, 169, 172, 177, 179*-*81, 184, 186*-*7, 194, 282*

private *1, 48* silent *2, 46, 173* Genotypes *9*/*8, 29, 40, 45, 48, 165*-*5, 168, 173, 179* GLP (Good Laboratory Practice) *5, 217, 223, 229, 255, 295* Glucose *3, 13, 51, 62* Glycoproteins *8, 10, 13, 15, 40, 144, 178, 182, 188* Glycosytransferase *2, 23, 39* GMP (Good Manufacturing Practice) *6*/*4, 217*-*18, 221*-*2, 255, 295* GVHD (graft-versus-host disease) *13*/*10, 60, 74, 80, 134, 138, 154, 270, 272, 282*-*5, 287*

### **H**

300 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

EOPs (equipment operating procedure) *219, 237* EQA (External Quality Assessment) *221, 233*-*5, 239*

Equipment operating procedure (EOPs) *219, 237*

External quality assessment *221, 231, 233*-*4, 238, 244, 257*

prevention of *271*-*5*

Estimated blood volume see EBV

Extravascular hemolysis *199*-*202*

Factor VIII(FVIII) *137, 140, 160*-*1*

Fibrinogen *35, 61, 65, 131, 136*-*7, 145*-*7, 263*

EQA schemes *221, 233*-*5, 240* Equipment downtime *248, 257*

Erythropoietin *75, 129*

Fab portion *10*-*11, 203* Factor IX *10, 160*

Factor XI(FXI) *136, 161* Family replacement donor *71* Fc portion *10*-*11, 198, 203, 206, 211*

Fc receptors *17*-*18, 211* Fatal blood cells *115, 189* Fetal cells *122, 216* Fetal haemoglobin *123*-*3* Fetal RBCs *121*-*3*

Fibrinogen level *149, 153,*  Fisher Race *163, 167*-*8* Flow cytometry *123*-*4,* 

Foetal cells *103, 124*-*5*

Frozen plasma *62*-*3, 158*

Fya and fyb antigens *187*-*8*

Gamma/X-irradiated red cells *1 155*

**G**

**F**

Enzymes *5, 10, 28, 39, 48, 52, 83, 92, 109, 111, 161, 182*-*4, 186, 188*-*9, 193, 197, 200, 207*

FFP (Fresh frozen Plasma) *24*-*5, 60, 62*-*5, 85, 90, 133, 136*-*7, 141, 145*-*9, 152*-*3, 201, 220, 258, 265, 270*

FMH (Feto Maternal Haemorrhage) *17, 101*-*2, 118, 120*-*3, 125*-*6, 128, 142, 243, 262*

Fresh frozen plasma *24*-*5, 60, 62*-*5, 90, 133, 136*-*7, 141, 148, 152, 201, 258*

Fya *10, 20*-*1, 47, 80, 98, 104*-*8, 111*-*12, 114, 174, 187, 206, 262*

Fyb *10, 20*-*1, 45, 80, 98*-*9, 105*-*8, 111*-*12, 114, 174, 187, 206,* 

Frozen Plasma (FP) *24*-*5, 60, 62*-*5, 90, 133, 136*-*7, 141, 148, 152, 158, 201, 258*

Genes *20*/*14, 29, 39*-*40, 44*-*6, 48, 137, 167, 169, 172, 177, 179*-*81, 184, 186*-*7, 194, 282*

Errors *26, 30*-*1, 75, 84, 95, 140, 218*-*19, 223, 229, 231*-*2, 254, 257, 269, 271*-*4*

Haemoglobinuria *6*/*3, 199*-*201, 212*-*13, 265* Haemolysate *2*/*1, 289*-*90* Haemolysin *8*/*6, 24*-*6, 54, 79, 136, 158* Haemolytic transfusion reaction (HTR) *21*/*15, 61, 79, 84, 98, 100*-*2, 162, 180, 183*-*4, 186, 188, 190*-*1, 196, 199*-*01, 204, 272* Haemolytic transfusion reactions *12*/*8, 79, 98, 100*-*2, 183*-*4, 191, 200*-*1, 204, 272* Haemphilia *6*/*3, 140*-*2, 160*-*1* HAV (hepatitis A virus) *1, 88* HBV (hepatitis B virus) *4, 83, 88, 218, 225* HCV (hepatitis C virus) *4, 80, 82, 88, 225* HCV antibody *1, 82* HDN (Hemolytic disease of the Newborn *23*/*13, 43, 92, 104*-*5, 114, 119, 121, 126*-*7, 170, 173, 182*-*5, 188*- *92, 208, 260*-*1* Hemoglobinuria *2, 201, 212* Hemolysis *9*/*7, 31, 84, 92, 192*-*3, 199*-*200, 202, 212* Hemolytic transfusion reactions *4, 24, 166, 182, 190* Hepatitis *12*/*8, 69, 72, 80, 82*-*3, 88*-*9, 140, 225*-*7, 286* History of blood transfusion *2, 2, 294* HIV (human immunodeficiency virus) *10*/*9, 45, 92, 110, 127, 168, 172*-*3, 175, 178, 216* HLA (Human leukocyte antigen) *11*/*10, 48, 85*-*6, 98, 135, 150, 155, 157, 190, 280, 282* HLA genes *1, 282* Horizontal audit *2, 222, 237* HPA (human platelet antigens) *2, 150, 157* HSC *4*/*2 279*-*80, 283*-*4* HSCT (Hematopoietic stem cell transplant *4*/*3, 279*-*80, 283*-*4* HTR*,* see haemolytic transfusion reacti… *4*/*3, 279*-*80, 285, 287* Human Normal Immunoglobulin (HNIG) *1, 226* Hypothermia *84, 87*

### **I**

IAT (indirect antiglobulin test) *95, 100, 103*-*104, 120, 203, 206, 215*

IgG *5*-*6, 9*-*11, 14, 16*-*20, 22*-*24, 43*-*44, 54, 80, 85*-*86, 95*-*96, 103*-*104, 109, 111*-*119, 131, 137*-*138, 160, 166, 170, 173*-*174, 177, 182*-*184, 186, 188, 190*-*195, 197*-*207, 209*-*215, 259* IgM *5*-*6, 9*-*10, 14, 16*-*17, 19*-*20, 22, 31, 43, 84, 91, 93, 103, 109, 112, 166, 173*-*174, 177*-*184, 191, 193*-*195, 197*-*202, 204, 210, 212*-*214* Immune response*,* primary *16, 103* Immune response*,* secondary *16, 84* Immune system *14*-*15, 17*-*18, 23, 65, 81, 100, 102*-*104, 112, 135, 190, 201, 280, 282*-*285* Immunoglobulin *7, 11, 14*-*20, 61, 65, 86, 101*-*103, 115*-*124, 127*-*128, 133, 139, 142, 158*-*160, 166, 173, 180, 182*-*184, 188, 190*-*191, 197*-*198, 203, 210, 212, 226, 263* Informed consent *275* Intraoperative blood salvage *72*-*3, 145* Intravascular hemolysis *198*-*202, 212* Intravenous iron *81, 129, 130* IQA (Internal Quality Assessment) *233*-*35* IQC (internal quality control) *221, 232* Irradiated product *155* IVIG (Intravenous Immunoglobulin) *133, 139, 160*

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 303

**M**

**P**

Malaria *55, 60, 66*-*67, 81*-*82, 89, 100, 133, 142, 186, 188, 210*

NHFTR (Non-haemolytic febrile transfusion reaction *85*

PAD (Predeposit Autologous donation) *71,* ? *74*-*75*

PCH (Paroxysmal cold Hemoglobinuria) *193, 212*-*213* PCR (polymerase chain reaction) *81*-*83, 86, 227, 282, 48*

Phosphate *263, 294, 8, 11, 15, 22*-*27, 30, 35, 40*-*42, 51, 53*-*67*

products *81, 144, 158*-*159, 215, 294, 61*-*62*

Platelet count *86, 127, 138*-*139, 142, 146, 150*-*151, 153*-*154, 157, 287, 66*

Quality assurance *217*-*218, 221, 223, 228, 230*-*235, 245, 248*-*249, 253*-*255*

Placenta barrier *152*-*154, 157*-*161, 177*-*182, 198, 201*-*202, 206, 212*-*216, 243, 253, 258, 261*

Peripheral blood stem cell (PBSC) *85, 279, 284*

platelet-rich *59, 64, 133, 137*

components *62, 86, 214,*  derivatives *60, 139*-*140,* 

proteins *74, 133, 139, 158*-*159*

PCC (Prothrombin complex concentrate) *131, 141, 144, 148, 162*

MNS blood group system *181*-*84, 295204, 213*

Methyldopa *209, 211, 213, 215*

Packed cells*,* unit of *93*

PCR test *83, 227,* 

Plasma*,* 

Panel cells *94, 109*-*112, 114, 262*

Plasma*,* cryosupematant *63*

liquid *63*-*64* maternal *117, 126*

pooled *160* cells *15*-*16*

treated *158*

Platelet Rich Plasma *59, 64, 133, 137*

Plateletpheresis *56, 57, 60, 66, 137*

Platelet transfusions *85*-*86, 137*-*139, 150, 157*

Quality assurance system *218, 245, 253*-*254*

PPE (personal protective equipment) *223*-*225, 240*

Plasmapheresis *56*-*57, 60, 66*

Platelet units *85*

**Q**

Non-compliances *240*-*241, 259, 275* Non-remunerated donors *67, 71, 62*

### **J**

JK antigen *189* Jkb *20, 21, 45, 80, 98, 99,* 

### **K**

Kappa *14*-*16, 19* KB *20*-*21, 45, 80, 98*-*99, 105*-*108, 114, 121*-*124, 128, 189*-*190, 195, 202, 206, 255* KB test *121*-*123, 128* Kell *6, 10, 13*-*14, 17, 21, 45, 47, 48, 80, 92*-*93, 96*-*101, 105, 112, 114, 126*-*127, 156*-*157, 166, 176, 184*-*186, 195, 201*-*202, 207, 208, 216, 258, 261, 270, 295* Kell antigens *10, 101, 112, 166, 184*-*186* Kell Blood group system *48, 184, 186, 295* Kidd Blood Group *20, 189*-*190, 295*

### **L**

Land-steiner-Weiner (LW) *13*-*14, 111* Lea *6, 20*-*21, 98, 105, 109, 111, 114, 178, 180, 195,*  Leb *6, 20,* -*21, 98, 105*-*109, 111, 114, 178*-*180* Lectin *29, 34, 43, 197, 215* Leucodepletion *61*-*62, 80*-*81, 88, 156, 158* Lewis *13, 20*-*21, 45, 96, 105, 111, 114, 177*-*181, 195, 201, 206, 294* Lower ionic strength saline *7, 92, 94, 113, 166, 174, 192, 207* Lutheran antigens -*194*

### **M**

302 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

*170, 173*-*174, 177, 182*-*184, 186, 188, 190*-*195, 197*-*207, 209*-*215, 259*

*182*-*184, 188, 190*-*191, 197*-*198, 203, 210, 212, 226, 263*

Intraoperative blood salvage *72*-*3, 145* Intravascular hemolysis *198*-*202, 212*

IQA (Internal Quality Assessment) *233*-*35* IQC (internal quality control) *221, 232*

*195, 201*-*202, 207, 208, 216, 258, 261, 270, 295* Kell antigens *10, 101, 112, 166, 184*-*186* Kell Blood group system *48, 184, 186, 295* Kidd Blood Group *20, 189*-*190, 295*

Land-steiner-Weiner (LW) *13*-*14, 111*

Leucodepletion *61*-*62, 80*-*81, 88, 156, 158*

Lectin *29, 34, 43, 197, 215*

Lutheran antigens -*194*

Lea *6, 20*-*21, 98, 105, 109, 111, 114, 178, 180, 195,*  Leb *6, 20,* -*21, 98, 105*-*109, 111, 114, 178*-*180*

Lewis *13, 20*-*21, 45, 96, 105, 111, 114, 177*-*181, 195, 201, 206, 294* Lower ionic strength saline *7, 92, 94, 113, 166, 174, 192, 207*

IVIG (Intravenous Immunoglobulin) *133, 139, 160*

*193*-*195, 197*-*202, 204, 210, 212*-*214* Immune response*,* primary *16, 103* Immune response*,* secondary *16, 84*

Informed consent *275*

Irradiated product *155*

Jkb *20, 21, 45, 80, 98, 99,* 

JK antigen *189*

Kappa *14*-*16, 19*

KB test *121*-*123, 128*

**J**

**K**

**L**

Intravenous iron *81, 129, 130*

IgG *5*-*6, 9*-*11, 14, 16*-*20, 22*-*24, 43*-*44, 54, 80, 85*-*86, 95*-*96, 103*-*104, 109, 111*-*119, 131, 137*-*138, 160, 166,* 

Immunoglobulin *7, 11, 14*-*20, 61, 65, 86, 101*-*103, 115*-*124, 127*-*128, 133, 139, 142, 158*-*160, 166, 173, 180,* 

IgM *5*-*6, 9*-*10, 14, 16*-*17, 19*-*20, 22, 31, 43, 84, 91, 93, 103, 109, 112, 166, 173*-*174, 177*-*184, 191,* 

Immune system *14*-*15, 17*-*18, 23, 65, 81, 100, 102*-*104, 112, 135, 190, 201, 280, 282*-*285*

KB *20*-*21, 45, 80, 98*-*99, 105*-*108, 114, 121*-*124, 128, 189*-*190, 195, 202, 206, 255*

Kell *6, 10, 13*-*14, 17, 21, 45, 47, 48, 80, 92*-*93, 96*-*101, 105, 112, 114, 126*-*127, 156*-*157, 166, 176, 184*-*186,* 

Malaria *55, 60, 66*-*67, 81*-*82, 89, 100, 133, 142, 186, 188, 210* Methyldopa *209, 211, 213, 215* MNS blood group system *181*-*84, 295204, 213* NHFTR (Non-haemolytic febrile transfusion reaction *85* Non-compliances *240*-*241, 259, 275* Non-remunerated donors *67, 71, 62*

### **P**

Packed cells*,* unit of *93* PAD (Predeposit Autologous donation) *71,* ? *74*-*75* Panel cells *94, 109*-*112, 114, 262* PCC (Prothrombin complex concentrate) *131, 141, 144, 148, 162* PCH (Paroxysmal cold Hemoglobinuria) *193, 212*-*213* PCR (polymerase chain reaction) *81*-*83, 86, 227, 282, 48* PCR test *83, 227,*  Peripheral blood stem cell (PBSC) *85, 279, 284* Phosphate *263, 294, 8, 11, 15, 22*-*27, 30, 35, 40*-*42, 51, 53*-*67* Placenta barrier *152*-*154, 157*-*161, 177*-*182, 198, 201*-*202, 206, 212*-*216, 243, 253, 258, 261* Plasma*,* cryosupematant *63* Plasma*,*  liquid *63*-*64* maternal *117, 126* platelet-rich *59, 64, 133, 137* pooled *160* cells *15*-*16* components *62, 86, 214,*  derivatives *60, 139*-*140,*  products *81, 144, 158*-*159, 215, 294, 61*-*62* treated *158* proteins *74, 133, 139, 158*-*159* Plasmapheresis *56*-*57, 60, 66* Platelet count *86, 127, 138*-*139, 142, 146, 150*-*151, 153*-*154, 157, 287, 66* Platelet Rich Plasma *59, 64, 133, 137* Platelet transfusions *85*-*86, 137*-*139, 150, 157* Platelet units *85* Plateletpheresis *56, 57, 60, 66, 137* PPE (personal protective equipment) *223*-*225, 240*

### **Q**

Quality assurance *217*-*218, 221, 223, 228, 230*-*235, 245, 248*-*249, 253*-*255* Quality assurance system *218, 245, 253*-*254*

Quality Audits *237*-*238, 253* Quality control (QC) *60, 91, 155, 217*-*227, 229*-*233, 239*-*240, 245, 247, 251*-*253, 255, 257, 259* Quality control demands *60* Quality control requirements *221* Quality management *218, 224, 230, 234, 243, 245, 247*-*248, 250, 291* Quality management system *230, 243, 247*-*248, 291* Quality system *217, 222*-*223, 230*-*233, 235, 237, 242, 245, 248, 250*

Transfusion Medicine Made Easy for Students of Allied Medical Sciences and Medicine 305

Rh-negative *115, 123, 127, 166, 171* Rh-negative women *116*-*121, 128*

Rheumatoid Arthritis (RA) *113*

Rhnull *173*

Satellite bag *51, 62*-*64*

Storage lesion *51*-*52* Storage of red blood cells *51*

Sugars *17, 22*-*23, 39, 179* Sufhydryl reagents *112*

Tranexamic acid *130, 144*

Secretors *40, 41, 178, 180* serum group *27, 32*-*35, 91*

**S**

**T**

**U**

**V**

**W**

**Z**

VCJD risk *55*

Rh system *4, 113, 115, 163, 167, 172, 181, 186*

Risk assessment *224, 225, 235, 251, 287, 288*

Spin*,* immediate *33, 34, 92*-*94, 98, 171, 191, 205*

TABI (transfusion associated bacterial infection *133*

*189, 190, 191, 194, 199, 200, 204, 208, 214, 260, 261, 294* TTP (thrombotic thrombocytopenic purpura *136, 148, 153*

Substances*,* precursor *39, 178*-*179, 191*-*192*

Total quality Management (TQM) *245*

transfusion*,* autologous *71*-*72, 74, 145, 295*

Unexpected antibodies *179, 203, 215, 216*

West Nile virus (WNV) *72, 80, 90, 134*

Wharton's Jelly *38, 99, 263*

Zeta- *5*-*7, 11, 177* ZZAP *112, 114*

von willebrand factor (VWF) *136, 137, 140, 160*

Screening cells *30, 31, 33, 41, 92, 95, 105, 110, 113, 196, 215, 216, 261, 262*

Specificity *5, 7, 14, 15, 19, 21, 40, 98, 103, 174, 199, 204, 245, 253, 261, 262*

SOPs (Standard Operating Procedures) *217, 219, 220, 223, 224, 230, 255, 259, 273*

Transfuson reactions*4, 22, 74, 83, 85, 90, 92, 100, 101, 102, 114, 134, 135, 138, 166, 174, 176, 178, 181*-*183,* 

### **R**

RA (Rheumatoid Arthritis) *113, 211, 287* RAADP (routine antenatal anti-D prophylaxis *116*-*117, 121* Radiotherapy *129, 148, 152, 154, 280, 281* RBC agglutination *212* RBC antibodies *60, 100, 101, 103, 104, 112, 114, 262* RBC antigens *101, 102, 104, 262* RBC of donor blood *42* RBC storage *52* RBC units *86, 132* Reactions acute haemolytic *84* allergic *85, 2, 14, 18, 58, 83* urticaria *85* Reagent Antiserum *181, 216* quality control *253* anti-globulin *206* antisera *27, 127* polyspecific *113, 204, 213* Red cell antigens *20, 21, 101, 102, 138, 177, 206, 221, 261* membrane *4, 6, 7, 9*-*14, 39, 40, 163*-*166, 172, 179, 189, 197*-*202, 211, 213* preservation *49, 51, 62* transfusion *25, 80, 100*-*103, 112, 129*-*131, 152, 177, 178, 199, 213, 216, 24* antibody-coated *201* concentrated *144* sensitized *10, 96, 113, 205* antibodies *16* Rh *4*-*6, 10, 13, 14, 21, 26, 30, 31, 43*-*48, 54, 58, 79, 80, 91*-*94, 97*-*102, 104, 105, 113*-*123, 126*-*128, 294, 267, 270, 272, 274, 139, 142, 156, 157, 162*-*177, 181, 184, 186, 191, 195, 202, 205*-*208, 215, 216, 220, 221, 252, 260*-*262* Rh antibodies *5, 98, 122, 166, 173, 174, 176, 202* Rh antigens *13, 163, 165, 167, 168, 172, 173, 261*

Rh blood group *4, 13, 21, 117, 162, 165, 167, 175*

Rh-negative *115, 123, 127, 166, 171* Rh-negative women *116*-*121, 128* Rh system *4, 113, 115, 163, 167, 172, 181, 186* Rheumatoid Arthritis (RA) *113* Rhnull *173* Risk assessment *224, 225, 235, 251, 287, 288*

### **S**

304 Dr Osaro Erhabor (Ph.D, CSci, FIBMS) and Dr Teddy Charles Adias (Ph.D, FIBMS)

Quality management *218, 224, 230, 234, 243, 245, 247*-*248, 250, 291*

Quality system *217, 222*-*223, 230*-*233, 235, 237, 242, 245, 248, 250*

RAADP (routine antenatal anti-D prophylaxis *116*-*117, 121*

Quality management system *230, 243, 247*-*248, 291*

RBC antibodies *60, 100, 101, 103, 104, 112, 114, 262*

RA (Rheumatoid Arthritis) *113, 211, 287*

Radiotherapy *129, 148, 152, 154, 280, 281*

acute haemolytic *84* allergic *85, 2, 14, 18, 58, 83*

Antiserum *181, 216* quality control *253* anti-globulin *206* antisera *27, 127*

polyspecific *113, 204, 213*

preservation *49, 51, 62*

antibody-coated *201* concentrated *144*

antibodies *16*

sensitized *10, 96, 113, 205*

Rh antibodies *5, 98, 122, 166, 173, 174, 176, 202* Rh antigens *13, 163, 165, 167, 168, 172, 173, 261* Rh blood group *4, 13, 21, 117, 162, 165, 167, 175*

antigens *20, 21, 101, 102, 138, 177, 206, 221, 261*

membrane *4, 6, 7, 9*-*14, 39, 40, 163*-*166, 172, 179, 189, 197*-*202, 211, 213*

transfusion *25, 80, 100*-*103, 112, 129*-*131, 152, 177, 178, 199, 213, 216, 24*

Rh *4*-*6, 10, 13, 14, 21, 26, 30, 31, 43*-*48, 54, 58, 79, 80, 91*-*94, 97*-*102, 104, 105, 113*-*123, 126*-*128, 294, 267, 270, 272, 274, 139, 142, 156, 157, 162*-*177, 181, 184, 186, 191, 195, 202, 205*-*208, 215, 216, 220, 221, 252, 260*-*262*

RBC agglutination *212*

RBC of donor blood *42* RBC storage *52* RBC units *86, 132*

Reactions

Reagent

Red cell

RBC antigens *101, 102, 104, 262*

urticaria *85*

Quality control (QC) *60, 91, 155, 217*-*227, 229*-*233, 239*-*240, 245, 247, 251*-*253, 255, 257, 259*

Quality Audits *237*-*238, 253*

Quality control demands *60* Quality control requirements *221*

**R**

Satellite bag *51, 62*-*64* Screening cells *30, 31, 33, 41, 92, 95, 105, 110, 113, 196, 215, 216, 261, 262* Secretors *40, 41, 178, 180* serum group *27, 32*-*35, 91* SOPs (Standard Operating Procedures) *217, 219, 220, 223, 224, 230, 255, 259, 273* Specificity *5, 7, 14, 15, 19, 21, 40, 98, 103, 174, 199, 204, 245, 253, 261, 262* Spin*,* immediate *33, 34, 92*-*94, 98, 171, 191, 205* Storage lesion *51*-*52* Storage of red blood cells *51* Substances*,* precursor *39, 178*-*179, 191*-*192* Sugars *17, 22*-*23, 39, 179* Sufhydryl reagents *112*

### **T**

TABI (transfusion associated bacterial infection *133* Total quality Management (TQM) *245* Tranexamic acid *130, 144* transfusion*,* autologous *71*-*72, 74, 145, 295* Transfuson reactions*4, 22, 74, 83, 85, 90, 92, 100, 101, 102, 114, 134, 135, 138, 166, 174, 176, 178, 181*-*183, 189, 190, 191, 194, 199, 200, 204, 208, 214, 260, 261, 294* TTP (thrombotic thrombocytopenic purpura *136, 148, 153*

### **U**

Unexpected antibodies *179, 203, 215, 216*

### **V**

VCJD risk *55* von willebrand factor (VWF) *136, 137, 140, 160*

### **W**

West Nile virus (WNV) *72, 80, 90, 134* Wharton's Jelly *38, 99, 263*

### **Z**

Zeta- *5*-*7, 11, 177* ZZAP *112, 114*

### *Authored by Osaro Erhabor and Teddy Charles Adias*

This basic text is intended to optimise the training and practice of transfusion medicine in developing countries particularly in sub- Saharan Africa.

It is aimed at improving the knowledge and skills of allied medical and medical students, and other healthcare professionals involved in blood transfusion, empowering them to offer the best possible blood transfusion services to their patients.

This book is suitable not only for allied medical and medical students preparing for their examination in transfusion medicine but also for postgraduates preparing for examination in general medicine, haematology and transfusion science.

The chapters have been presented in an annotated and easy to understand format.

Transfusion Medicine Made Easy For Students of Biomedical Science, Allied Medical

Sciences and Medicine

Transfusion Medicine

Made Easy For Students

of Biomedical Science,

Allied Medical Sciences and

Medicine

*Authored by Osaro Erhabor* 

*and Teddy Charles Adias*

Photo by phive2015 / iStock