Transfusion medicine

• Patients receiving RBC transfusion without appropriately identifying and honoring their auto and alloantibodies have the potential for acute or delayed hemolytic transfusion reactions (Immunohematology 2014;30:153)
• Severity of hemolysis ranges from mild to severe
• Signs and symptoms of hemolysis include
  • Anemia
  • Fatigue
  • Pallor
  • Shortness of breath
  • Back pain
  • Dark urine
  • Fevers / chills
  • Hypotension
  • Oliguria / anuria / renal failure (CDC: National Healthcare Safety Network Biovigilance Component Hemovigilance Module Surveillance Protocol [Accessed 9 May 2023])
  • Peripheral blood smear may show spherocytes (see Peripheral smear images below)

Contributed by Melissa R. George, D.O.

A 74 year old man with relapsed acute myeloid leukemia (AML) currently on chemotherapy had a complicated clinical course following COVID-19 infection, with subsequent fungal pneumonia and septic shock. He had known red blood cell antibodies against E and P1. During his hospital course, he developed new reactivity. Anti-Jk^a was identified and about a month later, a peripheral blood smear was reviewed on the patient. The slide signed out by the clinical pathologist on service noted: "moderate anisopoikilocytosis with spherocytes, occasional ovalocytes and teardrop cells... The findings are consistent with patient's history of chemotherapy for AML. The presence of spherocytes, positive autocontrol, positive DAT at IgG phase and panreactive elution, is suggestive of a warm autoantibody."

The patient was transfused several packed red blood cell and platelet units in the past 90 days. What would be the next best step in pretransfusion compatibility testing?

1. Allogeneic adsorption
2. Autologous adsorption
3. Cold adsorption
4. Dithiothreitol (DTT) treatment

A. Allogeneic adsorption. In the setting of a warm autoantibody in a patient who already has alloantibodies and has been transfused within the past 90 days, allogeneic adsorption is the most appropriate next step. Answer B is incorrect because recent transfusion precludes autologous transfusion. Answer C is incorrect because the reactivity is seen at IgG phase and therefore at 37 °C, cold adsorption is not indicated. Answer D is incorrect because dithiothreitol (DTT) is useful for decreasing CD38 on red blood cells and therefore reducing / eliminating interference from daratumumab therapy often used in plasma cell myeloma and sometimes for pure red cell aplasia / delayed engraftment status post-bone marrow transplant. However, there is no indication from the clinical history that the patient is receiving this therapy.

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Reference: Adsorption studies

A type and screen in a 56 year old woman with newly diagnosed Waldenström macroglobulinemia reveals panreactivity at immediate spin phase only. The autocontrol is positive at immediate spin phase and the direct antiglobulin test (DAT) is positive for complement. No reactivity is seen at antihuman globulin (AHG) phase using polyethylene glycol (PEG) enhancement; the autocontrol at AHG phase is also negative. The patient has no history of transfusions and no prior history of red cell antibodies. What is the most likely next step(s) for the technologist to exclude any underlying alloantibody?

1. No additional testing is necessary
2. Repeat the DAT; the results are erroneous given the absence of a DAT positive for IgG
3. Send out for allogeneic adsorption studies
4. Send out for autologous adsorption studies

A. No additional testing should be necessary. The panel described above is most compatible with a cold autoantibody or cold agglutinin, likely secondary to the patient's diagnosis of Waldenström macroglobulinemia. Cold agglutinins that do not show reactivity at AHG phase are unlikely to be clinically significant (i.e., cause in vivo hemolysis). Even if there were an underlying cold alloantibody, this would be unlikely to be clinically significant in the absence of reactivity at AHG phase; therefore, no additional testing is needed. AHG crossmatch compatible units of RBCs can safely be issued to this patient. Answers B - D are incorrect because these tests are not indicated in this case.

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Reference: Adsorption studies

A 60 year old woman was recently admitted to the hospital. Below are pertinent laboratory and blood bank results.

  

Based on these results, which of the following is true?

1. Alloantibody to a high prevalence antigen is present
2. Cold autoantibody is present
3. Warm autoantibody is present
4. Without evidence of hemolysis, a warm autoantibody can be ruled out

C. Warm autoantibody is present. These serologic results indicate a warm autoantibody and the diagnosis of a warm autoantibody can be made based on these results alone. While warm autoantibodies have the potential to cause in vivo hemolysis, not all do. The diagnosis of warm autoimmune hemolytic anemia (WAHA), however, requires the presence of a warm autoantibody and evidence of in vivo hemolysis (e.g., drop in hemoglobin / hematocrit, elevated bilirubin, elevated LDH, decreased haptoglobin, peripheral smear findings). Answer D is incorrect because a warm autoantibody cannot be ruled out in the absence of hemolysis. Answer B is incorrect because immediate spin results were negative, which is not consistent with a cold autoantibody. Answer A is incorrect because in the case of an alloantibody or even multiple alloantibodies, panreactivity is common but the autocontrol would likely be negative.

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Reference: Adsorption studies