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Chapter: Clinical Anesthesiology: Perioperative & Critical Care Medicine: Fluid Management & Blood Component Therapy

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Human red cell membranes are estimated to con-tain at least 300 different antigenic determinants, and at least 20 separate blood group antigen systems are known.




Human red cell membranes are estimated to con-tain at least 300 different antigenic determinants, and at least 20 separate blood group antigen sys-tems are known. Fortunately, only the ABO and the Rh systems are important in the majority of blood transfusions. Individuals often produce antibodies (alloantibodies) to the alleles they lack within each system. Such antibodies are responsible for the most serious reactions to transfusions. Antibodies may occur “naturally” or in response to sensitization from a previous transfusion or pregnancy.


The ABO System


ABO blood group typing is determined by the pres-ence or absence of A or B red blood cell (RBC) surface antigens: Type A blood has A RBC antigen, type B blood has B RBC antigen, type AB blood has both A and B RBC antigens, and type O blood has neither A nor B RBC antigen present. Almost all individuals not having A or B antigen “naturally” produce antibodies, mainly immunoglobulin (Ig) M, against those missing antigens within the first year of life.

The Rh System

Th ere are approximately 46 Rhesus group red cell surface antigens, and patients with the D Rhesus antigen are considered Rh-positive. Approximately 85% of the white population and 92% of the black population has the D antigen, and individuals lack-ing this antigen are called Rh-negative. In contrast to the ABO groups, Rh-negative patients usually develop antibodies against the D antigen only after an Rh-positive transfusion or with pregnancy, in the situation of an Rh-negative mother delivering an Rh-positive baby.

Other Red Blood Cell Antigen Systems


Other red cell antigen systems include Lewis, P, Ii, MNS, Kidd, Kell, Duffy, Lutheran, Xg, Sid, Car-tright, YK, and Chido Rodgers. Fortunately, with some exceptions (Kell, Kidd, Duffy, and Ss), alloan-tibodies against these antigens rarely cause serious hemolytic reactions.



The purpose of compatibility testing is to predict and to prevent antigen–antibody reactions as a result of red cell transfusions.

ABO–Rh Testing


The most severe transfusion reactions are due to ABO incompatibility; naturally acquiredantibodies can react against the transfused (foreign) antigens, activate complement, and result in intra-vascular hemolysis. The patient’s red cells are tested with serum known to have antibodies against A and against B to determine blood type. Because of the almost universal prevalence of natural ABO anti-bodies, confirmation of blood type is then made by testing the patient’s serum against red cells with a known antigen type.


The patient’s red cells are also tested with anti- antibodies to determine Rh status. If the subject is Rh-negative, the presence of anti-D antibody is checked by mixing the patient’s serum against Rh-positive red cells. The probability of developing anti-D antibodies after a single exposure to the Rh antigen is 50–70%.

Antibody Screen

The purpose of this test is to detect in the serum thepresence of the antibodies that are most commonly

associated with non-ABO hemolytic reactions. The test (also known as the indirect Coombs test) requires 45 min and involves mixing the patient’s serum with red cells of known antigenic composi-tion; if specific antibodies are present, they will coat the red cell membrane, and subsequent addition of an antiglobulin antibody results in red cell aggluti-nation. Antibody screens are routinely done on all donor blood and are frequently done for a potential recipient instead of a crossmatch (below).


A crossmatch mimics the transfusion: donor red cells are mixed with recipient serum. Crossmatching serves three functions: (1) it confirms ABO and Rh typing, (2) it detects antibodies to the other blood group systems, and (3) it detects antibodies in low titers or those that do not agglutinate easily.

Type & Crossmatch versus Type & Screen


In the situation of negative antibody screen without crossmatch, the incidence of serious hemolytic reac-tion with ABO- and Rh-compatible transfusion is less than 1:10,000. Crossmatching, however, assures optimal safety and detects the presence of less com-mon antibodies not usually tested for in a screen. Because of the expense and time involved (45 min), crossmatches are often now performed before the need to transfuse only when the patient’s antibody screen is positive, when the probability of transfu-sion is high, or when the patient is considered at risk for alloimmunization.



When a patient is exsanguinating, the urgent need to transfuse may arise prior to completion of a crossmatch, screen, or even blood typing. If the patient’s blood type is known, an abbreviated cross-match, requiring less than 5 min, will confirm ABO compatibility. If the recipient’s blood type and Rhstatus is not known with certainty and transfu-sion must be started before determination, typeRh-negative (universal donor) red cells may be used.



Blood donors are screened to exclude medical con-ditions that might adversely affect the donor or the recipient. Once the blood is collected, it is typed, screened for antibodies, and tested for hepatitis B, hepatitis C, syphilis, and human immunodeficiency virus (HIV). A preservative–anticoagulant solu-tion is added. The most commonly used solution is CPDA-1, which contains citrateasan anticoagulant(by binding calcium), phosphate as a buffer, dex-trose as a red cell energy source, and adenosine asprecursor for adenosine triphosphate (ATP) syn-thesis. CPDA-1-preserved blood can be stored for 35 days, after which the viability of the red cells rapidly decreases. Alternatively, use of either AS-1 (Adsol) or AS-3 (Nutrice) extends the shelf-life to 6 weeks.


Nearly all units collected are separated into their component parts (ie, red cells, platelets, and plasma). In other words, whole blood units are rarely available for transfusion in civilian practice. When centrifuged, one unit of whole blood yields approxi-mately 250 mL of packed red blood cells (PRBCs) with a hematocrit of 70%; following the addition of saline preservative, the volume of a unit of PRBCs often reaches 350 mL. Red cells are normally stored at 1–6°C, but may be frozen in a hypertonic glyc-erol solution for up to 10 years. The latter technique is usually reserved for storage of blood with rare phenotypes.


The supernatant is centrifuged to yield platelets and plasma. The unit of platelets obtained generally contains 50–70 mL of plasma and can be stored at 20–24°C for 5 days. The remaining plasma super-natant is further processed and frozen to yield fresh frozen plasma; rapid freezing helps prevent inac-tivation of labile coagulation factors (V and VIII). Slow thawing of fresh frozen plasma yields a gelati-nous precipitate (cryoprecipitate) that contains high concentrations of factor VIII and fibrinogen. Once separated, this cryoprecipitate can be refrozen for storage. One unit of blood yields about 200 mL of plasma, which is frozen for storage; once thawed, it must be transfused within 24 h. Most platelets are now obtained from donors by apheresis, and a single platelet apheresis unit is equivalent to the amount of platelets derived from 6–8 units of whole blood. The use of leukocyte-reduced (leukoreduction) blood products has been rapidly adopted by many countries, including the United States, in order to decrease the risk of transfusion-related febrile reac-tions, infections, and immunosuppression.


Packed Red Blood Cells


Blood transfusions should be given as PRBCs, which allows optimal utilization of blood bank resources. Surgical patients require volume as well as red cells, and crystalloid or colloid can be infused simultane-ously through a second intravenous line for volume replacement.


Prior to transfusion, each unit should be care-fully checked against the blood bank slip and the recipient’s identity bracelet. The transfusion tubing should contain a 170-µm filter to trap any clots or debris. Blood for intraoperative transfusion should be warmed to 37°C during infusion, particularly when more than 2–3 units will be transfused; failure to do so can result in profound hypothermia. The additive effects of hypothermia and the typically low levels of 2,3-diphosphoglycerate (2,3-DPG) in stored blood can cause a marked leftward shift of the hemo-globin–oxygen dissociation curve  and, at least theoretically, promote tissue hypoxia.

Fresh Frozen Plasma


Fresh frozen plasma (FFP) contains all plasma proteins, including most clotting factors. Transfu-sions of FFP are indicated in the treatment of iso-lated factor deficiencies, the reversal of warfarin therapy, and the correction of coagulopathy asso-ciated with liver disease. Each unit of FFP gener-ally increases the level of each clotting factor by 2–3% in adults. The initial therapeutic dose is usu-ally 10–15 mL/kg. The goal is to achieve 30% of the normal coagulation factor concentration.


FFP may also be used in patients who have received massive blood transfusions  and continue to bleed following platelet transfusions. Patients with antithrombin III deficiency or throm-botic thrombocytopenic purpura also benefit from FFP transfusions. Each unit of FFP carries the same infectious risk as a unit of whole blood. In addition, occasional patients may become sensitized to plasma proteins. ABO-compatible units should generally be given but are not mandatory. As with red cells, FFP should generally be warmed to 37°C prior to transfusion.


Platelet transfusions should be given to patients with thrombocytopenia or dysfunctional platelets in the presence of bleeding. Prophylactic plate-let transfusions are also indicated in patients with platelet counts below 10,000–20,000 × 109/L because of an increased risk of spontaneous hemorrhage.

Platelet counts less than 50,000 × 109/L are associated with increased blood loss during surgery. Thrombocytopenic patients often receive prophylac-tic platelet transfusions prior to surgery or invasive procedures. Vaginal delivery and minor surgical pro-cedures may be performed in patients with normal platelet function and counts greater than 50,000 × 109/L. Administration of a single unit of platelets may be expected to increase the platelet count by 5000– 10,000 × 109/L, and with administration of a platelet apheresis unit, by 30,000–60,000 × 109/L.


ABO-compatible platelet transfusions are desir-able but not necessary. Transfused platelets gener-ally survive only 1–7 days following transfusion. ABO compatibility may increase platelet survival. Rh sensitization can occur in Rh-negative recipients due to the presence of a few red cells in Rh-positive platelet units. Moreover, anti-A or anti-B antibod-ies in the 70 mL of plasma in each platelet unit can cause a hemolytic reaction against the recipient’s red cells when a large number of ABO-incompatible platelet units is given. Administration of Rh immu-noglobulin to Rh-negative individuals can protect against Rh sensitization following Rh-positive plate-let transfusions.

Granulocyte Transfusions


Granulocyte transfusions, prepared by leukapher-esis, may be indicated in neutropenic patients with bacterial infections not responding to antibiotics. Transfused granulocytes have a very short circu-latory life span, so that daily transfusions of 1010granulocytes are usually required. Irradiation ofthese units decreases the incidence of graft-versus-host reactions, pulmonary endothelial damage, and other problems associated with transfusion of leu-kocytes , but may adversely affect gran-ulocyte function. The availability of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has greatly reduced the use of granulocyte transfusions.

Indications for Procoagulant Transfusions


Blood products can be misused in surgical settings. Use of a transfusion algorithm, particularly for com-ponents such as plasma, platelets, and cryoprecipi-tate, and particularly when the algorithm is guided by appropriate laboratory testing, will reduce unnec-essary transfusion of these precious (but dangerous) resources . Derived from military experience, there is a trend in major trauma care towards transfusing blood products in equal ratios early in resuscitation in order to preempt or cor-rect trauma-induced coagulopathy. This balanced approach to transfusion of blood products, 1:1:1 (one unit of FFP and one unit of platelets with each unit of PRBCs) is termed damage control resuscita-tion .

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