What are the causes of acquired hemophilia?

Causes of Acquired Hemophilia A

Acquired hemophilia A is caused by autoantibodies against factor VIII, with approximately 50% of cases being idiopathic and the remaining 50% associated with identifiable underlying conditions including autoimmune diseases, malignancies, pregnancy/postpartum state, medications, and infections. 1, 2, 3

Idiopathic Cases

• Approximately 50% of acquired hemophilia A cases remain idiopathic with no identifiable underlying cause, making this the single most common "etiology" category 1, 2, 3
• These cases occur most commonly in elderly patients, with male preponderance in non-pregnancy-related cases 1

Autoimmune Diseases

• Autoimmune conditions are well-established triggers for factor VIII autoantibody development, including systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders 1, 2
• The autoimmune mechanism involves polyclonal immunoglobulin G directed against factor VIII procoagulant activity 1

Malignancy

• Both solid tumors and lymphoproliferative diseases are associated with acquired hemophilia A 1, 4
• Malignancy represents one of the major identifiable underlying disorders in non-idiopathic cases 2

Pregnancy and Postpartum State

• Pregnancy-related acquired hemophilia A typically occurs in the postpartum period, with female preponderance in this specific subgroup 1, 3
• This represents a distinct clinical entity with different demographic characteristics compared to other causes 1

Medications

• Drug-induced factor VIII autoantibodies have been documented with multiple medication classes, including antibiotics, psychiatric drugs, and immunomodulatory agents 4
• Interferon therapy for hepatitis C virus infection has particularly strong evidence for association with acquired hemophilia A 4
• A systematic review identified 34 cases of drug-induced factor VIII autoantibodies, with mean inhibitor titers of 67.7 Bethesda Units/mL 4
• The prognosis for drug-induced cases is generally favorable, with 83.3% complete remission rate after drug discontinuation or immunosuppressive therapy 4

Immune Checkpoint Inhibitors

• Immune checkpoint inhibitor therapy can cause acquired hemophilia A as an immune-related adverse event, requiring specific management protocols 5
• This represents an increasingly recognized cause given the expanding use of immunotherapy in oncology 5

Infections

• Infections are recognized as potential triggers for factor VIII autoantibody development, though less commonly reported than other causes 3, 4

Clinical Implications

• The elderly population is at highest risk for acquired hemophilia A across all etiologies 1, 6
• Mortality is high (ranging from 20-41% depending on treatment), making identification of underlying causes and prompt treatment essential 7
• Even when no underlying cause is identified initially, thorough evaluation for malignancy, autoimmune disease, and medication exposure is warranted 1, 2