Abstract

Background: Acquired hemophilia is a rare, often life-threatening, bleeding diathesis caused by autoantibodies, most commonly directed against factor VIII:C. Several clinical studies have reported mortality rates of 16–22 % for affected patients depending on age, inhibitor titre levels, and individual response to treatment. Patients in whom the inhibitor could not be eliminated had a mortality rate of 42 %, providing a strong argument for the necessity of rapid and long-term inhibitor elimination as part of the therapeutic concept. To date, no general consensus exists on the best therapeutic approach.

Patients and Methods: The history and clinical course of ten consecutive patients (4 females, 6 males, mean age [± SD] 61 ± 7 years) diagnosed for acquired hemophilia A in our department are reviewed with special regard to efficacy and side-effects of treatment. Initial treatment consisted of corticosteroids (1 mg/kg) in combination with either azathioprin (1.5 mg/kg, n=7) or cyclophosphamide (1.5 mg/kg, n=3). Severe bleeding complications were treated by recombinant factor VIIa (NovoSeven).

Results: On admission, mean inhibitor titres [± SD] were 83 ± 116 Bethesda units (BU) per milliliter with a range from 10–333 BU. Six of the 10 patients had concomitant disease (chronic obstructive lung disease [n=3], rheumatoid arthritis [n=2], sarcoidosis [n=1]). Immunosuppressive therapy had to be switched from azathioprin to cyclophosphamide in 4 of 7 patients during the clinical course because of treatment-associated hepatitis. Seven of the 10 patients achieved complete remission defined as return to normal factor VIII:C activity and undetectable factor VIII inhibitor titres. Remarkably, the period until complete remission in 2 patients with inhibitor titres above 200 BU was longer (mean 4 months vs. 6 to 8 weeks). Two patients are on immunosuppressive treatment since two months only and experienced a decrease in inhibitor titres, but no increase in factor VIII:C yet. Immunosuppressive therapy was complicated by infection (n=2), development of insulin-dependent diabetes mellitus (n=2), and vertebral fractures (n=1).

Conclusion: Our experience in this limited number of patients demonstrates that immunosuppressive treatment with corticosteroids and cytotoxic agents yields high response rates in acquired hemophiliacs. However, the high frequency of side-effects has to be carefully considered, particularly in elderly patients. In addition, elimination of inhibitors may be delayed specifically in patients with high inhibitor titres, increasing the cumulative risk of bleeding and treatment-associated toxicity.

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