Red Blood Cell Transfusion

Anemia is a common complication in patients with hematologic malignancies. The symptoms of anemia in any given patient can be variable, depending on several, often independent factors: the hemoglobin level, the rapidity of the development of the anemia, the patient's age, and the presence of underlying dis-ease.1 In general, red blood cell transfusion is indicated to relieve or prevent the signs and symptoms of hypoxemia. Ideally, the decision to transfuse should be individualized and appropriate for each patient and his or her disease process.1-3 Anemia is usually not associated with significant symptoms until the hemoglobin concentration is less than 7 or 8 g/dL. Symptoms are also related to the rapidity of the fall in hemoglobin concentration and the patient's ability to maintain a normal blood volume. In general, red cell transfusion is usually not indicated when the hemoglobin concentration is >10 g/dL, but it is usually indicated when the hemoglobin concentration is <7 g/dL.1-3

Guidelines for the appropriate use of red cell transfusions have been developed and published by several physician groups.4-6 Common general principles include the following: (1) the cause of anemia should be determined prior to transfusion, if possible, and appropriate specific or alternative therapy instituted (e.g., iron for anemia secondary to iron deficiency, vitamin B12 for anemia secondary to vitamin B12 deficiency, etc.); (2) clinical judgment for the need for transfusion should be used rather than a universal or automatic "trigger" hemoglobin level for transfusion; (3) a determination and assessment of those symptoms that are to be alleviated should be made; (4) an assessment of the patient's intravascular blood volume should be done and any volume deficiency restored with crystalloid or colloid solutions; (5) patients with underlying cardiovascular or respiratory diseases may need to maintain a hemoglobin concentration >10 g/dL; and (6) the risks and benefits of the transfusion should be discussed with the patient (i.e., informed consent).

Providing compatible red blood cells for transfusion to patients with cancer who have not undergone stem cell transplantation is usually not significantly different than transfusion for any other patient with anemia. The usual principles of specimen collection, serum antibody screening, and crossmatching apply. In general, approximately 3% of all patients transfused with red cells will form an alloantibody to one or more of the foreign red cell antigens.7 However, approximately 25% of alloantibodies will decrease in titer over time and may no longer be detectable in routine sero-logical tests.8 If the patient should again be challenged by the specific foreign antigen, an anamnestic response and subsequent hemolytic transfusion reaction may result. Although patients with hematologic malignancies may be immunosuppressed, they may still form red cell alloantibodies following transfusion.

The patient who has undergone an ABO incompatible hematopoietic stem cell transplantation presents unique challenges in providing compatible transfusion support. Approximately 30-40% of patients undergoing an allogeneic hematopoietic stem cell transplantation will receive an ABO incompatible graft from their donors.9-11 A major ABO mismatch between the donor and recipient is present when a foreign ABO antigen is introduced into the patient. A typical example would be, a group O recipient receiving a transplant from a group A, B, or AB donor.910 In a major ABO mismatch, the recipient has preformed circulating anti-A and/or anti-B isohemagglutinin that could potentially react with newly introduced ABO antigen on the stem cells or on contaminating donor red blood cells. The production of anti-A and/or anti-B may continue for several months following the transplant.91012-14 Red cells used for transfusion must, therefore, be compatible with both the donor and the recipient. Group O red cells can be given to all major ABO-incompatible recipients in order to avoid confusion.

A minor ABO mismatch involves the introduction of foreign anti-A and/or anti-B isohemagglutinins or lymphocytes capable of producing anti-A or anti-B after engraftment.9-11 An example is a group A recipient who receives group O or B stem cells (or a group B recipient who receives group O or A stem cells, or a group AB recipient who receives group O, A, or B donor stem cells).

Combined major and minor ABO mismatch occurs when a group A recipient receives group B cells, or when a group B recipient receives group A stem cells.910 In addition, other antigen mismatches (e.g., in the Rh system) may be important in certain clinical situations.1516 Passenger lymphocytes from the donor graft may also produce non-ABO antibodies, with resulting immune hemolysis.15-17

Major, minor, and combined major and minor ABO mismatched stem cell transplantation can be associated with acute or delayed hemolysis following transfusion of donor cells.910 Acute hemolysis following a major ABO mismatched transplantation can generally be avoided by removing the incompatible red cells prior to transfusion of the graft. Immune hemolysis complicates approximately 10-15% of minor ABO incompatible stem cell transplants.11 Delayed immune hemolysis can be seen following minor ABO incompatibility, when the transplanted passenger lymphocytes recognize the recipient's A or B antigen as foreign and actively produce anti-A or anti-B. This scenario is more likely to occur when the donor is group O and the recipient is group A or B and is characterized by the onset of immune hemolysis approximately 7-10 days after transplantation. The risk of immune hemolysis following minor ABO incompatibility appears to increase when the donor is unrelated or when cyclosporin is the sole agent used to prevent graft-versus-host disease (GVHD). While the majority of cases of immune hemol-ysis following minor ABO incompatibility are self-limited and last for 2 weeks or less, rare cases of severe hemol-ysis following minor ABO incompatibility have been fatal.11 As noted above, non-ABO antibodies may also be produced by passenger lymphocytes and result in clinically significant immune hemolysis. Guidelines for blood product selection in the stem cell transplant setting are shown in Table 104.1.

Stem cell transplant patients can also suffer acute or delayed hemolytic transfusion reactions secondary to the usual causes for this adverse reaction (e.g., misidentification of blood crossmatching specimens, patient identification errors, laboratory testing errors, etc.) and it should not be assumed that hemolysis is simply secondary to the engraftment of an ABO mismatched bone marrow.10 Other causes for hemolysis, such as thrombotic thrombocytopenic purpura (TTP), can also complicate the clinical course of patients with hematologic malignancy or stem cell transplantation.

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