International recommendations on the diagnosis and treatment of acquired hemophilia A
Andreas Tiede,
Peter Collins,
Paul Knoebl,
Jerome Teitel,
Craig Kessler,
Midori Shima,
Giovanni Di Minno,
Roseline d’Oiron,
Peter Salaj,
Victor Jiménez-Yuste,
Angela Huth-Kühne,
Paul Giangrande
Affiliations
Andreas Tiede
Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany
Peter Collins
Arthur Bloom Haemophilia Centre, University Hospital of Wales School of Medicine, Cardiff University, Cardiff, UK
Paul Knoebl
Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria
Jerome Teitel
Division of Hematology and Oncology, St. Michael's Hospital, Toronto, and Department of Medicine, University of Toronto, Toronto, Canada
Craig Kessler
Georgetown University Hospital, Lombardi Cancer Center, Division of Hematology/Oncology, Washington, DC, USA
Midori Shima
Department of Pediatrics, Nara Medical University, Nara, Japan
Giovanni Di Minno
Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy
Roseline d’Oiron
Centre de Référence de l'Hémophilie et des Maladies Hémorragiques Constitutionnelles Rares, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre APHP, Le Kremlin-Bicêtre, France
Peter Salaj
Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Victor Jiménez-Yuste
Hematology Department, La Paz University Hospital, Autonoma University, Madrid, Spain
Angela Huth-Kühne
SRH Kurpfalzkrankenhaus Heidelberg GmbH and Hemophilia Center, Heidelberg, Germany
Paul Giangrande
Green Templeton College, University of Oxford, Oxford, UK
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 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 activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII 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 5 weeks, with considerable interindividual 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.
