Blood transfusions

Red blood cell transfusions:

Red blood cell transfusions are given to raise the hematocrit levels in patients with anemia or to replace blood losses after acute bleeding episodes. Several types of components containing red blood cells are available.

(1) Fresh whole blood: The advantage of this component is the simultaneous presence of red blood cells, plasma, and fresh platelets. Fresh whole blood is never absolutely necessary, since all the above components are available separately. The major indications for use of whole blood are cardiac surgery or massive hemorrhge when more than ten units of blood are required in a 24-hour period.

(2) Packed red blood cells: Packed red blood cells are the component most commonly used to raise the hematocrit. Each unit has a volume of about 300mL, of which approximately 200mL consists of red blood cells. One unit of packed red cells will usually raise the hemotocrit by approximately 4%. The expected rise in hematocrit can be calculated using an estimated red blood cells volume of 200mL/unit and a total blood volume of about 70 mL/kg. For example, a 70 kg man will have a total blood volume of 4900mL, and each unit of packed red blood cells will raise the hematocrit by 200 4900=4%.

(3) Leucopoor blood: Patients with severe leukoagglutination reactions to packed red blood cells may require depletion of white blood cells and platelets from the transfused units. White blood cells can be removed either by centrifugation or by washing. Preparation of leukopoor blood is expensive and leads to some loss of red cells.

(4) Frozen blood(red blood cells) : Red blood cells can be frozen and stored for up to 3 years, but the technique is cumbersome and expensive, and frozen blood should be used sparingly. The major application is for the purpose of maintaining of a supply of rare blood types. Patients with such types may donate units for autologous transfusion  should the need arise. Frozen red cells are also occasionally needed for patients with severe leukoagglutination reactions or anaphylactic reactions to plasma proteins, since frozen blood has essentially all white blood cells and plasma components removed.

(5) Autologous packed red blood cells: Patients scheduled for elective surgery may donate blood for autologous transfusion. These units may be stored for up to 35 days.

Compatibility testing:

Before transfusion, the recipient's and the donar's blood are cross-matched to avoid hemolytic transfusion reactions. Although many antigen systems are present on red blood cells, only the ABO and Rh systems are specifically tested prior to all transfusions. The A and B antigens are the most important, because everyone who lacks one or both red cell antigens has isoantibodies against the missing antigen or antigens in his or her plasma. These antibodies  activate complement and can cause rapid intravascular lysis of the incompatible red cells. In emergencies, type O blood can be given to any recipient, but only packed cells should be given to avoid transfusion  of donor plasma containing anti-A or anti-B antibodies.

   The other important antigens routinly tested for is the D antigen of the Rh system. Approximately 15% of the population lack this antigen. In patients lacking the antigen, anti-D antibodies are not natually present, but the antigen is highly immunogenic. A recipient whose red cells lack D and who receives D-positive blood may develop anti-D antibodies that can cause severe lysis of subsequent transfusions of D-positive red cells.

   Hemolytic transfusion reactions

The most severe reactions are those involving mismatches in the ABO system. Most of these cases are due to clerical errors and mislabeled specimens. Hemolysis is rapid and intravascular, releasing free hemoglobin into the plasma. The severity of these reactions depends on the dose of red cells given. The most severe reactions are those seen in surgical patients under anesthesia.

     Hemolytic transfusion reactions caused by minor antigens systems are typically less severe. The hemolysis usually takes place at a slower rate and is extravascular. Sometimes these transfusion reactions may be delayed for 5-10 days after transfusion. In such cases, the recipient has received blood containing an immunogenic action, and in the time since transfusion, a new alloantibody has been formed. The most common antigens involved in such reactions are Duffy, Kidd, Kell, C and E loci of Rh system.

A.Symptoms and signs: Major hemolytic transfusion reactions cause fever and chills, with backpain and headache. In severe cases, there may be apprehension, dyspnea, hypotension, and vascular collapse. The transfusion must be stopped immediately. In severe cases, dissiminated intravascular coagulation, acute renal  failure from acute tubular necrosis, or both can occur.

      Patients under general anesthesia will not give such signs, and the first indication may be generalized bleeding and oliguria.

B. Laboratory findings: Identification of the recipient and of the blood should be checked. The donor transfusion bag with its pilot tube must be returned to the blood bank, and a fresh sample of recipient's blood must accompany the donor bag for retyping of donor and recipient blood samples and for repeat of the cross-match.

     The hematocrit will fail to rise by the expected amount. Coagulation studies may reveal evidence of renal failure and dissiminated intravascular coagulation. Hemoglobinemia will turn the plasma pink and eventually result in hemoglobinuria. In cases of delayed hemolytic reactions, the hematocrit will fall and the indirect bilirubin will rise. In these cases, the new offending alloantibody is easily detected in the patient's serum.

C. Treatment: If a hemolytic transfusion reactions is suspected, the transfusion should be stopped at once. A sample of anticoagulated blood from the recipient should be centrifuged to detect free hemoglobin in the plasma. If hemoglobinemia is present, the patient should be vigorously hydrated to prevent acute tubular necrosis. Forced diuresis with mannitol may help prevent renal damage.

Leucoagglutination reactions

    Most transfusion reactions are not hemolytic but represent reactions to antigens present on white blood cells in patients who have been sensitized to the antigens through previous transfusions or pregnancy. Most commonly, patients will develop fever and chills within 12 hours after transfusion. In severe cases, cough and dyspnea may occur and the chest x-ray may show transient pulmonary infilterates. Because no hemolysis is involved, the hemotocrit rises by the expected amount despite the reaction.

     Leucoagglutination reactions may respond to acetaminophen and diphenhydramine, corticosteriods are also of value. Removal of leucocytes by filteration before blood storage will reduce the incidence of these reactions.

Anaphylactic reactions 

      Rarely, patients will develop urticaria or bronchospasm during a transfusion. These reactions are almost always due to plasma proteins rather than white blood cells. Patients who are IgA-deficient may develop these reactions because of antibodies to IgA. Patients with such reactions may require transfusion of washed or even frozen red blood cells to avoid future severe reactions.

Contaminated blood

     Rarely, blood is contaminated with gram-negative bacteria. Transfusion can lead to septicemia and shock from endotoxin. If this is suspected. the offending unit should be cultured and the patients treated with antibiotics as indicated.

Diseases Transmitted Through Transfusion

     Despite the use of only volunteer blood donors and the routine screening of blood, transfusion-associated viral diseases remain a problem. All blood products(red cells, platelets, plasma, cryoprecipitate) can transmit viral diseases. All blood donors are screened with questionnaire designed to detect donors at high risk of transmitting diseases. All blood is now routinely screened with a variety of tests including hepatitis B surface antigen, antibody to HCV, antibody to HIV, and syphilis.

     With improved screening, the risk of post-transfusion hepatitis has steadily decreased. The major infectious risk of blood products is hepatitis C, with a seroconversion rate of 1:3300 per unit transfused. Most of these cases are clinically silent, but there is a high incidence of chronic hepatitis C.

Platelet Transfusion

     Platelet transfusions are indicated in cases of thrombocytopenia due to decreased platelet production. They are not useful in immune thrombocytopenia, since transfused platelets will last no longer than the patient's endogenous platelets. The risk of spontaneous bleeding rises when the platelet count falls to less than 10,000/uL, and the risk of life-threatening bleeding increases when the platelet count is less than 5000/uL. Because of this, prophylactic platelet transfusions are often given at these very low levels. Platelet transfusions are also given prior to invasive procedures or surgery, and the goal should be to raise the platelet count to over 50,000/uL.

     Platelets are most commonly derived from donated blood units. One unit of platelets(derived from 1 unit of blood) usually contains 5-7 10 platelets suspended in 35 mL of plasma. Ideally, 1 platelet unit will raise the recipient's platelet count by 10,000/uL, and transfused platelets will last for 2 or 3 days. However, responses are often suboptimal, with poor platelet increments and short survival times. This may be due to sepsis, splenomegaly, or alloimmunization. Most alloantibodies causing platelet destruction are directed at HLA antigens. Patients requiring long periods of platelet transfusion support should be monitored to decument adequate responses to transfusions so that the most appropriate product can be used. Patients may benefit from HLA-matched platelets derived from either volunteer donors or family members, with platelets obtained by platelet-pheresis. Techniques of cross-matching platelets have been developed and appear to identify suitable platelet donors (nonreactive with the patient's serum) without the need for HLA typing. Such single-donor platelets usually contain the equilevalent of 6 units of random platelets, or 30-50 10 platelets suspended in 200mL of plasma. Ideally, these platelet concentrates will raise the recipient's platelet count by 60,000/uL. Leucocyte depletion of platelets has been shown to delay the onset of alloimmunization.

Granulocyte Transfusions 

     Granulocyte transfusions are seldom indicated and have largely been replaced by the use of myeloid growth factors (G-CSF and GM-CSF) that speed neutrophil recovery. However, they may be beneficial in patients with profound neutropenia (<100/uL) who have gram-negative sepsis or progressive soft tissue infection despite optimal antibiotic therapy. In these cases, it is clear that progressive infection is due to failure of host defenses. In such situations, daily granulocyte transfusions should be given and continued until the neutrophil count rises to above 500/uL. Such granulocytes must be derived from ABO-matched donors. Although HLA matching is not necessary, it is preferred, since patients with alloantibodies to donor white cells will have severe reactions and no benefit.

     The donor cells usually contain some immunocompetent lymphocytes capable of producing graft-versus-host disease in HLA-incompatible hosts whose immunocompetenece may be impaired. Irradiation of the units of cells with 1500cGy will destroy the lymphocytes without harm to the granulocytes or platelets.

Plasma Components transfusion

      Fresh-frozen plasma is available in units of approximately 200mL. Fresh plasma contains normal levels of all coagulation factors (about 1 unit/mL). Fresh frozen plasma is used to correct coagulation factor deficiencies and to treat thrombotic thrombocytopenic purpura. The risk of transmitting viral diseases is compatible to that associated with transmission of red blood cells.

     Cryoprecipitate is made from fresh plasma. One unit has a volume of approximately 20mL and contains approximately 250 mg of fibrinogen and between 80 and 100 units of factor VIII and von willebrand factor. Cryoprecipitate is used to supplement fibrinogen in cases of congenital deficiency of fibrinogen or dissiminated intravascular coagulation. One unit of cryoprecipitate will raise the fibrinogen level by about 8mg/dl.