**3.4 Erythrocytes' substitutes**

These are substances able to replace the use of allogeneic blood components. They are obtained from human blood, transgenic animals or recombinant technology. Currently still under development. There are hemoglobin solutions and perfluorocarbonate emulsion.

### **3.5 Pharmaceutical measurements**

Several prohemostatic drugs have been used in order to try reducing or preventing intraoperative bleeding. In orthopedic surgery, antifibrinolytic and desmopressin are the mainly used.

### **3.5.1 Antifibrinolytics**

Perioperative bleeding is partially attributed to the fibrinolytic system activation. Several work groups have administered antifibrinolytics, and as a result observed a decrease in perioperative bleeding and blood bags transfused (Henry et al., 2001). In other recent revisions, which evaluate antifibrinolytics drugs in orthopedic surgery ( Kagoma et al., 2009; Zufferey et al., 2006), they conclude that using tranexamic acid or aprotinin reduces the percentage of patients requiring blood transfusions and also are efficient decreasing bleeding. When using epsilon-aminocaproic acid (EACA) there are no signs of a significant reduction in hemorrhagic risk, although not many studies have been done. All of them can have relatively infrequent but very serious side effects, such as arterial thrombosis, renal failure or rhabdomyolysis.

#### **3.5.1.1 Aprotinin**

It is a 58 amino acid polypeptide. It is found mainly in mammalian mastocytes and it is commercialized from bovine lung. Aprotinin works inhibiting trypsin, plasmin and tissue and plasma kallikrein. In addition to this, it holds an anti-inflammatory effect attenuating inflammatory response in major surgery, particularly at high-doses. It is the antifibrinolytic drug most widely studied to reduce bleeding and diminish transfusion needs. However, in comparison to tranexamic acid or EACA, it increases mortality risk. After the adverse results in mortality in patients who had undergone cardiac surgery in an observational study over more than 4000 patients (Mangano et al., 2006), and in a randomized double blind trial with over 3000 patients (Fergusson et al., 2008), the drug was withdrawn worldwide.

#### **3.5.1.2** *Synthetic antifibrinolytics*

Synthetic analogs of lysine. Tranexamic acid and EACA are able to block fibrinolysis by competitively antagonizing the binding of plasminogen to fibrin.

*Tranexamic acid* is 10 times stronger in vitro than EACA. In total knee arthroplasty, prophylactic administration significantly reduces blood loss up to 50% and decreases transfusion requirements without increasing the risk of thromboembolic signs (Alvarez et al., 2008; Cid & Lozano, 2005; Lozano et al., 2008). Optimal technique would be with two tranexamic acid bolus (each of them 10-15 mg/Kg), one before surgery and another when letting the air out of the tourniquet. In total hip prosthesis, tranexamic acid results in a

Blood Transfusion in Knee Arthroplasty 115

crystalloid contribution leads to their accumulation on the interstitial space during postoperative time and it is currently considered as an obsolete technique, mostly because of its inefficiency as a blood-saver method. Nowadays the use of normovolemic hemodilution is not recommended for decreasing allogeneic blood transfusion, nor transfused patient

Retrieving intraoperative blood involves autologous collection and infusion of autologous red blood cells, which is done by means of a device known as cell saver. It is commonly used in orthopedic surgery (spinal surgery and replacement of hip prosthesis) and provides significant autologous blood volumes. In major orthopedic surgery, perioperative blood retrieval reduces the probability of receiving autologous blood transfusion by 65% (Carless et al., 2004). The devices used recover only 50-60% of lost blood during surgery, which together with the high cost of consumables, makes its use only indicated to those procedures in which intraoperative hemorrhage is predicted to be over 1,000-1,500 ml, or else when it is possible to recover at least one packed red blood cells. This method would also be indicated in those patients whose religious believes contraindicates a blood donor transfusion but permits an autologous transfusion, when no compatible blood donor is available or when the patient is not capable of donating enough amount of autologous blood before surgery. Despite the devices' costs, retrieved and processed blood can be less expensive than allogeneic blood (Gardner et al., 2000). A clear benefit from perioperative blood reinfusion is the erythrocyte viability in collected blood, which is higher than that from allogeneic blood and oxygen transport capacity, being better than in stored blood (Colwell, Jr. et al., 2002). However, autotransfusion programs are associated with certain organization complexity

This procedure is contraindicated when there is bacterial contamination at the operating field, neoplastic disease, patients with positive viral-markers, sickle-cell anemia and when certain local hemostatics have been used or else when blood is found to be hemolyzed. Different procedures are available for intraoperative blood recovery. Semicontinuous-flow blood centrifugation system is one of the most commonly used, where blood is retrieved by aspiration, anticoagulated, filtered and sent to a reservoir from where it is pumped to a centrifuge bell which divides and washes the cells to return them to the patient as a saline suspended red blood cells, with a hematocrit value around 50-70%. During this process, plasma is dismissed, as well as toxic products from hemolysis, coagulation factors, platelets and fat. OrthoPAT® (Orthopedic Perioperative Autotransfusion System, Haemonetics), is an autologous blood retrieval, specifically designed for adapting to intermittent bleeding during and after programmed orthopedic surgery, reducing unnecessary allogeneic transfusions. It is a small device, easy to operate and completely automatized. In prosthetichip and spinal surgery it is commonly used for intra and postoperative retrieval, whereas in prosthetic-knee surgery it is preferably used postoperatively. Perioperative use of blood retrievals may significantly reduce allogeneic transfusion risks in a not inconsiderable

There are certain orthopedic surgical procedures (such as knee arthroplasty), in which postoperative bleeding through postsurgical drainages is very significant due to the

and a weak cost-benefit relationship when used indiscriminately.

number of patients with high-risk of being transfused (Pola et al., 2004).

**4. Postoperative strategies** 

**4.1 Postoperative autotransfusion** 

number or bags transfused.

**3.6.2 Intraoperative blood savers** 

decrease of intraoperative bleeding when administered prophylactically (Benoni et al., 2001), with no raise in thromboembolic complications incidence (Johansson et al., 2005b). However, it must only be used in those patients of whom a significant blood loss is expected. In spinal surgery, its administration is associated with considerable decrease in perioperative blood loss without side effects coming out (Elwatidy et al., 1976).

The rapid administration causes hypotension and its use is not recommended in patients with thromboembolic history although there is no evidence of an association with thromboembolic complications arising.

*Epsilon-aminocaproic acid (EACA)*, in addition to its antifibrinolytic effect, prevents from platelet receptor degradation by plasmin, preserving platelet function. On the whole, recommended dose is a 150-mg/Kg bolus before surgery, followed by a 15-mg/Kg/h infusion during surgery. In a 2008-published meta-analysis they concluded that it is the most effective antifibrinolytic drug in spinal surgery (Gill et al., 2008). Nevertheless, not many studies have been done regarding this drug as to obtain conclusions. The most frequent side effect is hypotension, which is usually associated to a rapid intravenous administration. There is no evidence that EACA would raise thromboembolic episodes.

### **3.5.2 Desmopressin acetate**

Desmopressin acetate is an antidiuretic hormone synthetic analogue. Besides its antidiuretic effect, it has a hemostatic action that would be based in factor VIII and Von Willebrand factor release to the circulatory system from the existent deposits at the vascular endothelium cells, and its ability for increasing platelet adhesion. In orthopedic surgery its use has been reduced mainly to spinal surgery, with initial encouraging results (Kobrinsky et al., 1987), although not proved in subsequent studies. In hip and knee orthopedic surgery there is no evidence of a decrease in blood loss or erythrocyte volume transfusion. Dose for intravenous administration is 0.3 g/Kg and its main use would be for Von Willebrand syndrome. Desmopressin side effects include facial redness, severe headache, hypotension and high-speed beating. Its strong antidiuretic effect can produce water retention, hyponatremia and convulsions.

### **3.6 Autotransfusion**

It includes all the procedures by which a patient is transfused with his own blood. These methods have a number of advantages such as lack of infectious diseases transmission, avoids hemolytic disease incidence and several different transfusion reactions, it has immediate availability, as well as compatibility, avoids categorization and cross-matching mistakes, and last of all, decreases hypothermal risk of stored blood. It can be performed by two different methods:

#### **3.6.1 Normovolemic hemodilution**

Normovolemic hemodilution consists in extraction and anticoagulation of an established blood volume (4 units maximum) after anesthetic induction and its simultaneous substitution for crystalloids and/or colloids to maintain normovolemia, and thus causing dilutional anemia. Reinfusion is done later on when surgical hemorrhage is under control or even before if necessary. Extracted blood is then anticoagulated at room temperature, which preserves platelet functions. Despite these theoretical benefits, dissolving coagulation factors, hematocrit and platelets causes a microvascular bleeding. Furthermore, excessive

decrease of intraoperative bleeding when administered prophylactically (Benoni et al., 2001), with no raise in thromboembolic complications incidence (Johansson et al., 2005b). However, it must only be used in those patients of whom a significant blood loss is expected. In spinal surgery, its administration is associated with considerable decrease in

The rapid administration causes hypotension and its use is not recommended in patients with thromboembolic history although there is no evidence of an association with

*Epsilon-aminocaproic acid (EACA)*, in addition to its antifibrinolytic effect, prevents from platelet receptor degradation by plasmin, preserving platelet function. On the whole, recommended dose is a 150-mg/Kg bolus before surgery, followed by a 15-mg/Kg/h infusion during surgery. In a 2008-published meta-analysis they concluded that it is the most effective antifibrinolytic drug in spinal surgery (Gill et al., 2008). Nevertheless, not many studies have been done regarding this drug as to obtain conclusions. The most frequent side effect is hypotension, which is usually associated to a rapid intravenous administration. There is no evidence that EACA would raise thromboembolic episodes.

Desmopressin acetate is an antidiuretic hormone synthetic analogue. Besides its antidiuretic effect, it has a hemostatic action that would be based in factor VIII and Von Willebrand factor release to the circulatory system from the existent deposits at the vascular endothelium cells, and its ability for increasing platelet adhesion. In orthopedic surgery its use has been reduced mainly to spinal surgery, with initial encouraging results (Kobrinsky et al., 1987), although not proved in subsequent studies. In hip and knee orthopedic surgery there is no evidence of a decrease in blood loss or erythrocyte volume transfusion. Dose for intravenous administration is 0.3 g/Kg and its main use would be for Von Willebrand syndrome. Desmopressin side effects include facial redness, severe headache, hypotension and high-speed beating. Its strong antidiuretic effect can produce water retention,

It includes all the procedures by which a patient is transfused with his own blood. These methods have a number of advantages such as lack of infectious diseases transmission, avoids hemolytic disease incidence and several different transfusion reactions, it has immediate availability, as well as compatibility, avoids categorization and cross-matching mistakes, and last of all, decreases hypothermal risk of stored blood. It can be performed by

Normovolemic hemodilution consists in extraction and anticoagulation of an established blood volume (4 units maximum) after anesthetic induction and its simultaneous substitution for crystalloids and/or colloids to maintain normovolemia, and thus causing dilutional anemia. Reinfusion is done later on when surgical hemorrhage is under control or even before if necessary. Extracted blood is then anticoagulated at room temperature, which preserves platelet functions. Despite these theoretical benefits, dissolving coagulation factors, hematocrit and platelets causes a microvascular bleeding. Furthermore, excessive

perioperative blood loss without side effects coming out (Elwatidy et al., 1976).

thromboembolic complications arising.

**3.5.2 Desmopressin acetate** 

hyponatremia and convulsions.

**3.6 Autotransfusion** 

two different methods:

**3.6.1 Normovolemic hemodilution** 

crystalloid contribution leads to their accumulation on the interstitial space during postoperative time and it is currently considered as an obsolete technique, mostly because of its inefficiency as a blood-saver method. Nowadays the use of normovolemic hemodilution is not recommended for decreasing allogeneic blood transfusion, nor transfused patient number or bags transfused.

### **3.6.2 Intraoperative blood savers**

Retrieving intraoperative blood involves autologous collection and infusion of autologous red blood cells, which is done by means of a device known as cell saver. It is commonly used in orthopedic surgery (spinal surgery and replacement of hip prosthesis) and provides significant autologous blood volumes. In major orthopedic surgery, perioperative blood retrieval reduces the probability of receiving autologous blood transfusion by 65% (Carless et al., 2004). The devices used recover only 50-60% of lost blood during surgery, which together with the high cost of consumables, makes its use only indicated to those procedures in which intraoperative hemorrhage is predicted to be over 1,000-1,500 ml, or else when it is possible to recover at least one packed red blood cells. This method would also be indicated in those patients whose religious believes contraindicates a blood donor transfusion but permits an autologous transfusion, when no compatible blood donor is available or when the patient is not capable of donating enough amount of autologous blood before surgery.

Despite the devices' costs, retrieved and processed blood can be less expensive than allogeneic blood (Gardner et al., 2000). A clear benefit from perioperative blood reinfusion is the erythrocyte viability in collected blood, which is higher than that from allogeneic blood and oxygen transport capacity, being better than in stored blood (Colwell, Jr. et al., 2002). However, autotransfusion programs are associated with certain organization complexity and a weak cost-benefit relationship when used indiscriminately.

This procedure is contraindicated when there is bacterial contamination at the operating field, neoplastic disease, patients with positive viral-markers, sickle-cell anemia and when certain local hemostatics have been used or else when blood is found to be hemolyzed. Different procedures are available for intraoperative blood recovery. Semicontinuous-flow blood centrifugation system is one of the most commonly used, where blood is retrieved by aspiration, anticoagulated, filtered and sent to a reservoir from where it is pumped to a centrifuge bell which divides and washes the cells to return them to the patient as a saline suspended red blood cells, with a hematocrit value around 50-70%. During this process, plasma is dismissed, as well as toxic products from hemolysis, coagulation factors, platelets and fat.

OrthoPAT® (Orthopedic Perioperative Autotransfusion System, Haemonetics), is an autologous blood retrieval, specifically designed for adapting to intermittent bleeding during and after programmed orthopedic surgery, reducing unnecessary allogeneic transfusions. It is a small device, easy to operate and completely automatized. In prosthetichip and spinal surgery it is commonly used for intra and postoperative retrieval, whereas in prosthetic-knee surgery it is preferably used postoperatively. Perioperative use of blood retrievals may significantly reduce allogeneic transfusion risks in a not inconsiderable number of patients with high-risk of being transfused (Pola et al., 2004).
