Acute hemolysis after intravenous immunoglobulin amid host factors of ABO ‐mismatched bone marrow transplantation, inflammation, and activated mononuclear phagocytes

Background Hemolysis may follow intravenous immunoglobulin ( IVIG ), with product, dosing, and host factors contributing. The importance of recipient features remains unclear. Case Report A 52‐year‐old obese woman, 10 years after ABO ‐mismatched (recipient O , donor A ) marrow transplantation, presented with immune thrombocytopenia ( ITP ). IVIG at 100 g/day × 2 days was followed by hemoglobinuria and angina and dyspnea, with frank hemoglobinemia and anemia (hemoglobin 12.9 to 8.4 over 24 hr, to a nadir of 6.9 g/ dL ). Study Design and Methods Serologic methods established ABO , A 1, L ewis, and S ecretor type, while monocyte monolayer assay ( MMA ) examined erythrophagocytosis with control or patient monocytes, and the implicated IVIG lot to opsonize control (group A 1, A 2, B , O ) or patient red blood cells (RBCs). Baseline, hemolytic, and convalescent markers (including cytokines) were assessed. Results Passive anti‐ A was identified on reverse type and eluted from sensitized RBCs (immunoglobulin  G 1+, C 3d–). L e(a–b+) typing and saliva confirmed H S ecretor status. MMA revealed significant activity between patient RBCs, monocytes, and IVIG . However, normal A 1 cells opsonized with IVIG were not significantly phagocytosed by either normal or patient monocytes. Proinflammatory markers were significantly elevated before and after IVIG . Conclusions Synergizing host factors (including obesity‐unadjusted dosing and existing inflammation) marked this severe post‐ IVIG hemolytic crisis. Group A antigen restriction to myeloid tissues, with H S ecretor phenotype, may have contributed, rendering this bone marrow transplant chimera vulnerable to anti‐ A in a manner analogous to the idiosyncratic effect of therapeutic anti‐ D in certain D + ITP recipients. However, MMA suggested a macrophage activation state as contributory, perhaps precipitated by existing inflammation.