International recommendations on the diagnosis and treatment of acquired hemophilia A

Authors: Tiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, Di MG, d’ Oiron R, Salaj P, Jimenez-Yuste V, Huth-Kuhne A, and Giangrande P.

Publication: Haematologica;

Affiliations: Dept. of Hematology, Hannover Medical School, Hannover, Germany; Arthur Bloom Haemophilia Centre, University Hospital of Wales School of Medicine, Cardiff, UK; Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria Div. of Hematology and Oncology, St. Michael’s Hospital, Toronto and University of Toronto, Canada; Div. of Hematology/Oncology, Georgetown University Hospital, Lombardi Cancer Center, Washington; Department of Pediatrics, Nara Medical University, Nara, Japan Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy; Hopitaux Universitaires Paris Sud, Hopital Bicetre APHP, Le Kremlin-Bicetre, France Institute of Haematology and Blood Transfusion, Prague, Czech Republic; Haematology Department, La Paz University Hospital, Autonoma University, Madrid, Spain; SRH Kurpfalzkrankenhaus Heidelberg GmbH and Hemophilia Center, Heidelberg, Germany Green Templeton College, University of Oxford, Oxford, UK.

Abstract: Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time (APTT) due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged APTT should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injury that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII (rFVIIa), activated prothrombin complex concentrate (APCC), or recombinant porcine FVIII (rpFVIII) in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is five weeks, with considerable inter-individual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist, therefore, we provide practical consensus guidance based on recent registry findings and the authors’ clinical experience in treating patients with AHA.