Transfusion Reaction with Inconclusive Serology
A 45-year-old woman with a history of two pregnancies and no prior transfusions receives 2 units of packed RBCs for symptomatic anemia (Hb 7.0 g/dL) after surgery. Fifteen minutes into the second unit, she develops fever (38.5°C), chills, and flank pain. The transfusion is stopped immediately. The post-transfusion sample shows a positive antibody screen (3+ in gel) and a positive direct antiglobulin test (DAT) with anti-IgG (2+) and anti-C3d (1+). The eluate from the post-transfusion sample is nonreactive. The pre-transfusion antibody screen was negative. The unit was crossmatch-compatible by immediate spin and AHG. The patient's plasma reacts with all panel cells at AHG, but the reactivity is abolished by treating panel cells with ficin. The patient's own cells are DAT positive.
1. What is the most likely cause of the reaction, and what further testing should be performed?
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The clinical picture (fever, chills, flank pain) and serology (positive antibody screen, positive DAT, panreactivity at AHG that is ficin-sensitive) suggest a delayed hemolytic transfusion reaction (DHTR) due to an antibody against a high-incidence antigen, likely an antibody to a ficin-sensitive antigen such as Cartwright (Yt^a), Cromer, or Gerbich, or possibly an antibody to a low-incidence antigen that the patient was exposed to during pregnancy. However, the eluate being nonreactive is unusual for a DHTR; it may be due to the antibody being adsorbed onto the transfused cells or a prozone phenomenon. The ficin sensitivity indicates the antigen is a glycoprotein (e.g., glycophorin or band 3). Further testing should include: (1) Phenotype the patient's red cells for common antigens to rule out alloantibodies. (2) Perform a more extensive antibody identification panel, including enzyme-treated cells and possibly a selected cell panel to identify the antibody. (3) Test the patient's serum against the donor unit's red cells (if available) to see if the antibody reacts. (4) Consider testing for antibodies to low-incidence antigens using a capture technique or testing the patient's plasma against a panel of rare cells. (5) Perform a monocyte monolayer assay or other functional test if available. (6) Repeat the DAT and eluate with a more sensitive method. (7) Notify the blood bank and the clinician; the patient should receive least-incompatible blood if transfusion is needed, and future transfusions should be avoided if possible. The reaction should be reported to the blood bank and the hospital transfusion committee.
2. How should the blood bank manage future transfusion needs for this patient?
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The patient has an antibody to a high-incidence antigen, making it difficult to find compatible blood. The blood bank should: (1) Attempt to identify the specific antibody by testing against a large panel of rare cells or sending samples to a reference laboratory. (2) Once identified, search for antigen-negative units through the rare donor registry (e.g., American Rare Donor Program). (3) If compatible units are not available, consider using least-incompatible units (those that are crossmatch-compatible by AHG but may still be incompatible) after consultation with a transfusion medicine specialist, and premedicate with corticosteroids and antihistamines. (4) Monitor the patient closely during any transfusion and use leukoreduced units to prevent febrile reactions. (5) Document the antibody in the patient's record and provide a medical alert card. (6) Educate the patient about the need to inform all healthcare providers of the antibody. (7) Consider autologous donation if elective surgery is planned. (8) The blood bank should maintain a list of compatible donors for future needs.