Practice Essentials
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). [1] Acquired hemophilia can occur in the context of a variety of disorders, including autoimmune diseases and malignancies, or as a drug reaction, but approximately half of cases are idiopathic.
Signs and symptoms
Patients with acquired hemophilia may have no bleeding, mild bleeds, or life-threatening bleeds. [2] Most patients 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 activated partial thromboplastin time (aPTT) typically shows a prolongation that is not reversed on a correction study
- The bleeding time, prothrombin time (PT), and platelet count are normal
- 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, quantification of the level may may be useful in selecting hemostatic therapy in patients who require it
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
- Clinically relevant bleeding can be treated with recombinant FVIII porcine sequence (rpFVIII), if the baseline anti-porcine FVIII inhibitor titer is ≤ 20 BU; recombinant activated factor VII (rFVIIa); or activated prothrombin complex concentrate (APCC). The choice is determined by the agents’ availability and cost, and—for rpFVIII—baseline anti-porcine FVIII inhibitor titer and ability to monitor rpFVIII.
- If the patient has a low FVIII inhibitor level (< 5 BU) and other options are not available, human FVIII concentrates may be used to control bleeding; however, no dosing guides are available and massive doses may be required.
- Hemostatic prophylaxis is indicated for patients at high risk of bleeding and for invasive procedures (both minor and major); if possible, invasive procedures should be delayed until the inhibitor has been eradicated. Prophylaxis can be with rpFVIII, rFVIIa, APCC, or emicizumab (off label).
- 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 is with corticosteroids alone or combined with rituximab or cyclophosphamide.
- Salvage therapy with cyclosporine is particularly effective in patients with underlying systemic lupus erythematosus.