Key Takeaways

Acquired hemophilia A (AHA) is a rare autoimmune disease with high risk for morbidity and mortality.

AHA occurs most commonly in the elderly (median age 64–78), but it is also associated with pregnancy.

About 50% of patients have primary or idiopathic AHA (not associated with an underlying condition). The other 50% have secondary AHA, which may be associated with malignancy, autoimmune disease (SLE, RA), pregnancy, infections, or medications.

In contrast to congenital hemophilia A, AHA affects both males and females and occurs in the absence of a personal or family history of bleeding.

AHA is mediated by neutralizing immunoglobulin G (IgG) autoantibodies (inhibitors) targeting endogenous FVIII/

Suspect AHA in patient with unexplained bleeding and isolated elevation in aPTT, especially in the elderly and in pregnant women.

Confirm AHA by showing the inability of normal plasma to correct the prolonged aPTT in a mixing study (especially after 2 hour incubation), low factor VIII activity (FVIII:C) and a positive inhibitor assay (Bethesda, modified Bethesda or ELISA).

There are three pillars of treatment: control bleeding, eradicate the inhibitor and treat any underlying condition that may be causative.

About 70% of patients will require hemostatic treatment. First-line therapy consists of recombinant activated FVII or aPCC. Both are believed to be of comparable efficacy. If there is no response to the first agent within 12-24 hours, then switching to the second is advised. There are no specific tests for monitoring treatment with bypassing agents. Treatment is monitored by clinical assessment of bleeding.

Emicizumab, a recombinant, humanized, bispecific antibody that binds activated factor IX and factor X mimicking the function of FVIII is currently being studied in clinical trials.

All patients should receive immunosuppressive treatment (IST) to eradicate the inhibitor. First-line therapy is with glucocorticoids with or without cyclophosphamide or rituximab. Treatment response is monitored using inhibitor titer and FVIII levels. IST is generally withdrawn or tapered as soon as PR is achieved.

Complete remission is achieved by 60% to 90% of patients.

Relapse occurs in approximately 20% of patients.

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