A 68-year-old woman with newly diagnosed multiple myeloma is started on daratumumab-based induction. She requires a packed red blood cell transfusion. The blood bank reports a positive indirect antiglobulin test and pan-reactive antibody screen, despite no alloantibodies being identified. What is the mechanism of this laboratory finding?

• A Daratumumab causes hemolysis
• B Daratumumab activates the complement cascade directly
• C Daratumumab suppresses erythropoietin
• D Daratumumab binds to CD38 on reagent red cells ✓

Explanation

Daratumumab is an anti-CD38 monoclonal antibody. CD38 is expressed on reagent red blood cells used in antibody screening. Daratumumab binds to these cells, causing pan-reactivity on the indirect antiglobulin test. This can be mitigated by treating reagent cells with dithiothreitol which denatures CD38, allowing true alloantibodies to be detected.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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