ABO Discrepancy in Multiple Myeloma Initially Suspected as a Complication of COVID-19 Vaccination

The effect of COVID-19 infection and its vaccines on the immune system is still a subject of much research and debate. Caution is warranted to rule out known entities before considering these possibilities. We report a case of an incidentally detected ABO discrepancy initially suspected to be temporally associated with COVID-19 vaccination but diagnosed ultimately as multiple myeloma. A 52-year-old male patient presented with weakness, easy fatigability, and chest pain following the second dose of the COVID-19 vaccine. His hemoglobin fell progressively, and he was advised blood transfusion. Blood grouping revealed an ABO discrepancy in forward and reverse grouping. The initial indirect Coombs test (ICT) showed 3+ reactivity, possibly due to non-specific interference from elevated serum proteins, but the repeat test was negative. Routine peripheral blood smear examination showed rouleaux formation and background blue-tinging. Saline replacement dispersed the RBC aggregates, confirming pseudo-agglutination. The patient also had a raised erythrocyte sedimentation rate (ESR). The patient was suspected of having a plasma cell dyscrasia, which was confirmed on serum electrophoresis, and this explained the ABO discrepancy. M protein in plasma cell myeloma is known to cause group III ABO discrepancy due to rouleaux formation, which can be interpreted as pseudo-agglutination and can be a presenting feature. Though temporal association with vaccination may raise suspicion, a detailed work-up is necessary to avoid misattribution and missing underlying disease.