**3.1 Allogenic blood transfusion**

In cardiac surgery, blood transfusion is indicated to correct severe anaemia due to excessive bleeding caused by vessel disruption during surgical exposure and dissection or by coagulopathy. Severe anaemia is characterised by a decrease in Hb concentration which leads to diffuse or localised tissue ischaemia. The attitudes to indications for transfusion have developed under the influence of diverse subjective views, ranging from a miraculous remedy to an absolute refusal, as well as on evidence-based information. Patients can greatly benefit from blood transfusion, if it is life-saving, or be severely harmed if a serious infection is transferred. The risk of viral infection transfer has recently decreased so much (HIV or HCV transfer is one per million transfusions) that it should no longer be a limiting factor in blood transfusion [37].

Transfusion can also induce immunomodulation in the recipient, i.e., stimulation or inhibition of immune responses.. The former involves the production of antibodies (alloimmunisation) against the surface antigens including HLA, which has several adverse effects. The latter, immune depression, involves a decrease in the ratio of circulating T-lymphocyte subpopulations (CD4+/CD8+) and impaired function of natural killer cells and antibody production by lymphocytes. The development of immunomodulation is associated with donor leukocytes; their removal can by half reduce the incidence of adverse conditions, such as transfusion-related acute lung injury (TRALI) [38]. In addition, immunomodulation can enhance susceptibility to infection, as suggested by a strong association found between transfusion and post-operative infection in a retrospective study on 15 000 patients surgically treated for ischaemic heart disease in Cleveland in 2006 [39].

Blood transfusion offers three advantages: it increases blood oxygen-carrying capacity, provides volume to support cardiac output and improves homeostasis; however, only the first one is the indication criterion. Which situation, therefore, requires an increase in oxygen-binding capacity of the blood by means of transfusion? A defined threshold Hb concentration is not the answer, because the capacity of blood to transport oxygen depends on other parameters such as cardiac output, pulmonary oxygenation, and haemoglobin ability to bind and release oxygen. Nevertheless, based on studies and expert opinions, a consensus has been reached that transfusion is beneficial to patients with an Hb concentration below 7 g/dl while it brings no benefits to patients with an Hb level above 10 g/dl. Moreover, an increase in oxygen-carrying capacity by transfusion is not accompanied by an immediate increase in oxygen delivery to tissues, because stored erythrocytes are depleted of 2, 3-diphosphoglycerate and nitric oxide concentrations, which markedly reduces their ability to offload oxygen. To recover this ability takes several hours, and blood bank transfusion thus only adds to haemodilution of functional haemoglobin and a transient drop in oxygen supply.

the early phase of circulatory and haemostatic homeostasis, it is advisable to increase Hb concentration to 8g/dl in order to spare the compensatory capacity of myocardium (increased cardiac output) and to utilise a possibility to regulate systemic blood pressure by blood viscosity. In patients with serious peripheral arterial disease, it is reasonable to increase the transfusion trigger. Transfusion should be administered only after the patient's medical history and their actual health status have been taken into consideration

In cardiac surgery, blood transfusion is indicated to correct severe anaemia due to excessive bleeding caused by vessel disruption during surgical exposure and dissection or by coagulopathy. Severe anaemia is characterised by a decrease in Hb concentration which leads to diffuse or localised tissue ischaemia. The attitudes to indications for transfusion have developed under the influence of diverse subjective views, ranging from a miraculous remedy to an absolute refusal, as well as on evidence-based information. Patients can greatly benefit from blood transfusion, if it is life-saving, or be severely harmed if a serious infection is transferred. The risk of viral infection transfer has recently decreased so much (HIV or HCV transfer is one per million transfusions) that it should no longer be a limiting

Transfusion can also induce immunomodulation in the recipient, i.e., stimulation or inhibition of immune responses.. The former involves the production of antibodies (alloimmunisation) against the surface antigens including HLA, which has several adverse effects. The latter, immune depression, involves a decrease in the ratio of circulating T-lymphocyte subpopulations (CD4+/CD8+) and impaired function of natural killer cells and antibody production by lymphocytes. The development of immunomodulation is associated with donor leukocytes; their removal can by half reduce the incidence of adverse conditions, such as transfusion-related acute lung injury (TRALI) [38]. In addition, immunomodulation can enhance susceptibility to infection, as suggested by a strong association found between transfusion and post-operative infection in a retrospective study on 15 000 patients surgically treated for ischaemic heart disease in

Blood transfusion offers three advantages: it increases blood oxygen-carrying capacity, provides volume to support cardiac output and improves homeostasis; however, only the first one is the indication criterion. Which situation, therefore, requires an increase in oxygen-binding capacity of the blood by means of transfusion? A defined threshold Hb concentration is not the answer, because the capacity of blood to transport oxygen depends on other parameters such as cardiac output, pulmonary oxygenation, and haemoglobin ability to bind and release oxygen. Nevertheless, based on studies and expert opinions, a consensus has been reached that transfusion is beneficial to patients with an Hb concentration below 7 g/dl while it brings no benefits to patients with an Hb level above 10 g/dl. Moreover, an increase in oxygen-carrying capacity by transfusion is not accompanied by an immediate increase in oxygen delivery to tissues, because stored erythrocytes are depleted of 2, 3-diphosphoglycerate and nitric oxide concentrations, which markedly reduces their ability to offload oxygen. To recover this ability takes several hours, and blood bank transfusion thus only adds to haemodilution of functional haemoglobin and a transient

[36, 37].

**3.1 Allogenic blood transfusion** 

factor in blood transfusion [37].

Cleveland in 2006 [39].

drop in oxygen supply.

In healthy individuals, an acute anaemic state no longer manageable by compensatory mechanisms and leading to a switch to anaerobic metabolism occurs at Hb levels between 3 and 4 g/dl. This is associated with venous haemoglobin oxygen saturation of 56%, which equals to a tissue supply of 333 ml oxygen/min/m2. The major compensatory mechanisms include increased cardiac output, an increase in oxygen extraction and an increase in capillary erythrocyte transit time. Patients with coronary heart disease may develop acute anaemia at an Hb level of about 6 g/dl. These limit values have been obtained in animal experiments and confirmed by cardiac surgery in several thousands of Jehovah's Witness patients. The level of evidence, defined as C and D, allows us to accept the fact that, in certain clinical situations, patients can tolerate an Hb concentration of about 6 g/dl. The range of clinical conditions is very broad and, in the present-day ageing polymorbid population, there are not many patients who would tolerate acute anaemia with threshold Hb values 6 g/dl.

#### **3.2 Fresh frozen plasma (FFP)**

Full blood collected from donors is treated by plasmapheresis or centrifugation to obtain plasma which is frozen within 6 hours of collection. Although FFP is indicated for documented either isolated or multiple coagulation factor deficiencies (II, V, VII, IX, X, XII), it has formerly been used as volume replacement and in the prophylaxis of potential coagulopathy in relation to massive transfusions and extracorporeal circulation. At the 1984 conference on FFP it was concluded that such indications for FFP administration are not justified and this conclusion has so far been accepted [40,10]. Prophylactic FFP administration on the basis of massive transfusion (more than 10 red blood cell mass units) and abnormal laboratory tests (PT and aPTT) in the absence of clinically apparent bleeding is not supported by evidence either. Abnormal PT and aPTT results are often found even after five administrations of blood transfusion. Their positive predictive value is only about 30%. However, patients in whom the blood transfusion volume exceeds the total blood volume will always require either platelet substitution or FFP, or both products. A correlation between the volume of lost plus transfusion blood and the occurrence of coagulopathy is not a simple one. On the other hand, there is a strong correlation between the occurrence of coagulopathy and the duration of hypotension and/or hypothermia. Patients with no or only a short period of hypotension, even if they receive massive transfusion, will not have coagulopathy while those exposed to one hour of hypotension will often develop a serious form of it. Similarly, hypothermia plays an important role; its avoidance is a decisive factor in the prevention of coagulopathy after massive transfusion Patients undergoing cardiac surgery with extracorporeal circulation experience a drop in coagulation factor levels by 30 to 40 %, but only few of them show clinical bleeding. Excessive bleeding after cardiac surgery, if not due to surgical reasons, results from platelet dysfunction or their deficiency, and/or is caused by hypothermia, prolonged hypotension (circulatory shock) or residual heparinisation. Because of the lack of scientific evidence for clinical efficacy, indication criteria for the use of FFP are largely based on cardiac surgeons' expertise. They include: 1) substitution therapy in isolated or multiple coagulation factor deficiencies.; 2) need to reverse over-warfarinisation, in that case two units are administered in the non-bleeding patient and six units in the bleeding one; 3) treatment of pathological bleeding due to a transfusion volume being larger than the patient's total blood volume.
