Acquired hemophilia is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors, most frequently factor VIII (FVIII).

Signs and symptoms

Most patients with acquired hemophilia present with hemorrhages into the skin, muscles, or soft tissues and mucous membranes. Intra-articular bleeding episodes are uncommon.

Diagnosis

Laboratory study results in acquired hemophilia are as follows:

• The bleeding time, prothrombin time (PT), and platelet count are normal
• The activated partial thromboplastin time (aPTT) typically shows a prolongation that is not reversed on a correction study
• Reduced FVIII levels and evidence of an FVIII inhibitor are critical to the diagnosis of acquired hemophilia A
• Other factor levels should be determined to establish inhibitor specificity
• Once the acquired inhibitor is detected, it should be quantified to project the severity of the disorder and the risk of hemorrhagic complications

Testing to exclude lupus anticoagulant (eg, dilute Russell viper venom time and the kaolin clotting time) is indicated if aPTT values during the mixing study are similar at time 0 and after incubation at 37°C. Screening for heparin is also necessary.

Management

Therapeutic options in acquired hemophilia include the following:

• Treatment of the underlying disorder or discontinuation of an offending drug may eliminate or assist in the eradication of the inhibitor
• High-dose infusions of FVIII (eg, 200 IU/kg IV bolus q 8-12 h) may facilitate hemostasis in patients with low-titer inhibitors
• Patients with very low inhibitor titers (<3 Bethesda units [BU]) and residual FVIII activity may also benefit from treatment with desmopressin
• Moderate to severe bleeding in patients with inhibitor titers of less than 5 BU can be treated with recombinant FVIII porcine sequence (Obizur), which is approved for as it is less likely than human FVIII to be neutralized by the inhibitors that occur in acquired hemophilia A
• Patients with severe bleeding and inhibitor titers of 5 BU or higher should receive therapy with either recombinant factor VIIa or an activated prothrombin complex concentrate (APCC)
• Eradication of the inhibitor with immunosuppression should be initiated as soon as the diagnosis of acquired hemophilia is established
• First-line therapy for inhibitor eradication usually includes methylprednisolone at a dose of 1 mg/kg/day, or an equivalent dose of prednisone; adding oral cyclophosphamide (50-150 mg/d) can increase the response rate
• Rituximab may be considered in cases of resistance to or intolerance of standard immunosuppressive therapy
• Salvage therapy with cyclosporine is particularly effective in patients with underlying systemic lupus erythematosus