Case Report: Coexisting cold agglutinin disease and acquired hemophilia A: a rituximab-responsive dual autoimmune disorder

TL;DR

A 53-year-old man had two rare blood disorders that responded to rituximab, a B-cell targeting treatment, after failing other therapies.

Contribution

First documented case of concurrent cold agglutinin disease and acquired hemophilia A successfully treated with rituximab.

Findings

Rituximab resolved both coagulation and hemolytic issues after steroid failure.

B-cell targeted therapy showed therapeutic potential for overlapping autoimmune hematologic conditions.

Case highlights the importance of minimizing infection risks with targeted treatment strategies.

Abstract

This report describes the first documented case of concurrent cold agglutinin disease (CAD) and acquired hemophilia A (AHA) in a 53-year-old male presenting with recurrent hematuria, hematemesis, and cold-induced acrocyanosis. Diagnostic findings included severe anemia with hemoglobin of 61 g/L, markedly prolonged activated partial thromboplastin time (aPTT, 88.6 s), critically reduced factor VIII activity (1.4%), a factor VIII inhibitor titer of 3.6 Bethesda units, and an elevated cold agglutinin titer of 1:320. Initial immunosuppression with corticosteroids and cyclophosphamide failed to improve either the coagulopathy or hemolytic anemia, consistent with the recognized poor response of CAD to steroid therapy. Clinical deterioration occurred during steroid tapering, complicated by hospital-acquired pneumonia. Administration of rituximab (375 mg/m2 weekly for 4 weeks) resulted in simultaneous resolution of both autoimmune processes, with normalization of coagulation parameters and significant improvement in hemoglobin levels. This outcome aligns with established evidence supporting B-cell targeted therapy for autoimmune hematologic disorders. The case highlights the diagnostic challenges posed by overlapping autoimmune hematologic conditions and demonstrates the therapeutic potential of rituximab in simultaneously addressing both coagulation and hemolytic pathologies. It further underscores the importance of targeted treatment strategies that minimize infection risks associated with broad immunosuppression. This unique presentation advances our understanding of shared autoimmune mechanisms in hematologic disease and supports the use of early B-cell-directed therapy in complex autoimmune hematologic conditions.

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