Acquired Hemophilia A: Current Guidance and Experience from Clinical Practice

Abstract

In acquired hemophilia A (AHA), autoantibodies to coagulation factor VIII (FVIII) neutralize FVIII activity leading to a potentially severe bleeding diathesis that carries a high rate of morbidity and mortality. This disorder is rare and occurs mainly in adults over 60 years of age or in the postpartum period. The diagnosis should be suspected in patients with new-onset bleeding without a personal or family history of bleeding and can be confirmed via specific assays for FVIII inhibitors. Treatment involves both hemostatic therapies to decrease bleeding and immune modulation strategies to re-establish immune tolerance to FVIII. There are limited data on treatment for refractory disease, based mostly on small case series. Registry studies have informed consensus guidelines for optimal hemostatic therapies and initial immunosuppressive therapies. Additional studies are needed to evaluate novel hemostatic agents and develop biomarkers to risk-stratify treatment while limiting adverse events.

Keywords: autoantibodies; factor VIII; hemostasis; immune modulation.

Figure 1

Laboratory testing algorithm for suspected acquired hemophilia A. After exclusion of interfering substances as a cause of prolonged aPTT, a two-hour mixing study should be done with normal pooled plasma. For samples where the aPTT corrects, a factor deficiency should be suspected, and specific factor assays conducted. For samples where the aPTT does not correct, testing for lupus anticoagulant should be done and, if negative, specific testing for a FVIII inhibitor should be conducted. Inhibitors can be measured via Bethesda assay ideally with heat inactivation.