Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by spontaneous development of high-affinity neutralizing IgG autoantibodies (inhibitors) against coagulation factor VIII, leading to functional factor VIII deficiency and severe bleeding diathesis. Annual incidence is approximately 1.5 per million population. AHA has bimodal age distribution: postpartum young women (5-10% of cases, typically within 6 months of delivery) and older adults (>65 years, 50% of cases). Underlying associations identified in 50% of cases include autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis), malignancies (solid tumors and hematologic), pregnancy/postpartum, infections, drugs (penicillins, sulfonamides, interferon), dermatological conditions (pemphigus, psoriasis); 50% are idiopathic.
Clinical presentation differs significantly from congenital hemophilia A: AHA typically causes spontaneous mucocutaneous bleeding (skin, mucous membranes), large soft tissue and muscle hematomas, gastrointestinal and genitourinary bleeding, retroperitoneal bleeding (life-threatening), surgical bleeding, and intracranial hemorrhage. Joint bleeds (hemarthroses, hallmark of congenital hemophilia) are uncommon. Bleeding can be severe with mortality 9-22% at 1 year, particularly in older patients, those with high inhibitor titers, and those with underlying malignancy. Diagnosis requires: (1) clinical bleeding diathesis or laboratory finding of prolonged activated partial thromboplastin time (aPTT) not corrected by mixing with normal plasma (1:1 mixing); (2) low factor VIII activity (<1-50%); (3) presence of factor VIII inhibitor confirmed by Bethesda or Nijmegen-modified Bethesda assay (units measure inhibitor titer).
Treatment has two parallel goals: rapid hemostatic control of bleeding and immunosuppression for inhibitor eradication. Hemostatic agents bypass the inhibitor: recombinant activated factor VII (rFVIIa, NovoSeven, 90 mcg/kg every 2-3 hours initially) and activated prothrombin complex concentrate (aPCC, FEIBA, 50-100 U/kg every 8-12 hours, max 200 U/kg/day) are first-line bypassing agents; recombinant porcine sequence factor VIII (susoctocog alfa, OBI-1) is approved for AHA, providing direct factor VIII replacement with low cross-reactivity to anti-human factor VIII antibodies; emicizumab (bispecific antibody bridging FIXa and FX) under investigation but not standard; high-dose human factor VIII (50-100 U/kg) only for low-titer inhibitors (<5 BU). Immunosuppression for inhibitor eradication uses corticosteroids (prednisone 1 mg/kg/day) as first-line, often combined with cyclophosphamide (1-2 mg/kg/day for 4-6 weeks) for higher inhibitor titers; rituximab (anti-CD20, 375 mg/m2 weekly x4) is an effective second-line option, particularly for relapsed or refractory AHA; immunoglobulin not effective. Median time to remission is 4-7 weeks. Treatment of underlying conditions (malignancy, autoimmune disease) and discontinuation of triggering medications (when applicable) is essential. Patient should avoid invasive procedures, intramuscular injections, antiplatelets/anticoagulants, and aspirin until inhibitor eradicated and factor VIII activity normalized.