Hemolysis following Allogeneic BMT |
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An important complication of minor ABO-incompatible marrow transplants is known as the passenger Iymphocyte syndrome. Immune hemolysis of the recipient's red cells occurs as a result of anti-A and/or anti-B production by passenger Iymphocytes in the marrow product. Rarely, antibodies of other blood group systems, particularly Rh, may also cause hemolysis.
Minor incompatibility (e.g. group O donor marrow infused to group A recipient)
- The donor is capable of making antibodies against the recipient's RBC antigens.
- Passenger lymphocyte syndrome may occur in which anti-A &/or B is produced by rapidly proliferating passenger lymphocytes transfused with the donor marrow.
- Hemolysis occurs suddenly between days 5 & 15 after transplant - before engraftment & immune reconstitution.
- Patients experience intravascular hemolysis, rapidly decreasing hemoglobin & renal failure.
- Anti-A &/or B directed against recipient RBCs is detected in serum & on RBCs.
- Hemolysis subsides as patient's residual incompatible RBCs are destroyed & replaced by new RBCs of donor origin &/or transfused group O RBCs.
- At risk patients need to be monitored between days 5 & 15 after transplant by measuring hemoglobin, bilirubin, LD haptoglobin and direct antiglobulin test (DAT).
- If hemolysis is suspected, Blood Bank needs to be notified.
- It is very important to avoid transfusion of platelets with ABO incompatible plasma (see platelet protocol).
- If hemolysis occurs, appropriate management consists of transfusion of group O red cells.
- Occasionally a red cell exchange transfusion is indicated to replace the recipient's incompatible red cells with those that are group O.
The passenger Iymphocyte syndrome has also been reported after transplantation of kidney, liver, lung, pancreas and spleen. Accordingly, recipients of minor-ABO blood group incompatible solid organ transplants should also be observed for signs of hemolysis and anti-A and/or anti-B antibody production during the first two weeks after transplantation. When hemolysis occurs, transfusion with group O red cells is indicated as in marrow transplants.
Major incompatibility (e.g. group A donor marrow infused to group O recipient)
- The recipient is capable of making antibodies against donor's RBC antigens.
- Most cases are prevented by RBC depletion of the marrow before infusion.
- Delayed hemolysis may occur when there is persistence of recipient's anti-A &/or B.
- Hemolysis occurs more often in patients being treated with cyclosporine.
- Hemolysis begins between days 35 & 105 after transplant and can persist for 10 to 100 days.
- High titer anti-A &/or B inhibit erythropoiesis & may cause RBC aplasia.
- As anti-A &/or B titer decreases, erythropoiesis occurs but RBCs are hemolyzed by the persistent antibody.
- Hemolysis resolves with disappearance of patient's anti-A &/or B.
- At risk patients need to be monitored between days 35 & 105 for hemoglobin, bilirubin, LD, haptoglobin and DAT.
Autoimmune Hemolytic Anemia
- Hemolysis is due to antibodies produced by donor's lymphocytes against RBCs of donor origin.
- AIHA has occurred with matched sibling & matched unrelated donors. It may occur more commonly with T cell depleted marrow grafts.
- Hemolysis begins 7 to 25 months after transplant & is often resistant to therapy.
- Patients need to be monitored after the 7th month for hemoglobin, bilirubin, LD, haptoglobin and direct antiglobulin test (DAT).
Thrombotic Thrombocytopenic Purpura & Hemolytic Uremic Syndrome
- TTP-HUS is associated with total body irradiation, chemotherapeutic & immunosuppressive drugs, and bone marrow or solid organ transplant.
- TTP-HUS usually develops at a median of 5 months (range 3 - 7 months) after transplant.
- Lack of RBC antibodies & presence of fragmented RBCs on peripheral smear distinguish TTP-HUS from immune hemolysis.
Passive Transfer of Antibody
- The most common sources are plasma of donor marrow, platelet transfusions & intravenous immunoglobulin.
- Hemolysis occurs immediately after infusion of large volumes of these products.
References
Benjamin RJ & Antin JH. ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity. Transfusion 1999; 39:1273-74.
Benjamin RJ, McGuirk S, Ralston MS et al. ABO incompatiblity as an adverse risk factor for survival after allogeneic bone marrow transplantation. Transfusion 1999; 39:179-87.
Heal JM & Blumberg N. The second century of ABO: and now for something completely different. Transfusion 1999; 39:1155-59.
Lee EJ and Schiffer CA. ABO compatibility can influence the results of platelet transfusion. Transfusion 1989; 29:384-89.
Larsson LG, Welsh VJ & Ladd DJ. Acute intravascular hemolysis secondary to out-of-group platelet transfusion. Transfusion 2000; 40:902-06.
Lasky LC, Warkentin PI, Kersey JH et al. Hemotherapy in patients undergoing blood group incompatible bone marrow transplantation. Transfusion 1983; 23:277.
McManigal SM & Sims KL. Intravascular hemolysis secondary to ABO incompatible platelet products. Am J Clin Pathol 1999;111:202-206.
Petz, LP. Immunohematologic problems associated with bone marrow transplantation. Transfusion Medicine Reviews 1987;1:85-100.
Petz LP. Hemolysis associated with transplantation. Transfusion 1998;38:224-28.
Salmon JP, Michaux S, Hermanne JP et al. Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation. Transfusion 1999; 39:824-27.
Worel N, Greinix HT, Schneider B et al. Regeneration of erythropoiesis after related- and unrelated- donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems. Transfusion 2000; 40:543-550.
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