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International recommendations on the diagnosis and treatment of acquired hemophilia A
Ferrata Storti Foundation
Haematologica 2020 Volume 105(7):1791-1801
Andreas Tiede,1 Peter Collins,2 Paul Knoebl,3 Jerome Teitel,4 Craig Kessler,5 Midori Shima,6 Giovanni Di Minno,7 Roseline d’Oiron,8 Peter Salaj,9 Victor Jiménez- Yuste,10 Angela Huth-Kühne11 and Paul Giangrande12
1Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany; 2Arthur Bloom Haemophilia Centre, University Hospital of Wales School of Medicine, Cardiff University, Cardiff, UK; 3Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria; 4Division of Hematology and Oncology, St. Michael's Hospital, Toronto, and Department of Medicine, University of Toronto, Toronto, Canada; 5Georgetown University Hospital, Lombardi Cancer Center, Division of Hematology/Oncology, Washington, DC, USA; 6Department of Pediatrics, Nara Medical University, Nara, Japan; 7Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy; 8Centre de Référence de l'Hémophilie et des Maladies Hémorragiques Constitutionnelles Rares, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre APHP, Le Kremlin-Bicêtre, France; 9Institute of Hematology and Blood Transfusion, Prague, Czech Republic; 10Hematology Department, La Paz University Hospital, Autonoma University, Madrid, Spain; 11SRH Kurpfalzkrankenhaus Heidelberg GmbH and Hemophilia Center, Heidelberg, Germany and 12Green 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 due to FVIII deficiency. Neutralizing anti- bodies (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 com- plex 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.
Introduction
Acquired hemophilia A (AHA) is characterized by neutralizing autoantibodies, called inhibitors, against factor VIII (FVIII).1 AHA is a rare disorder, affecting men and women of all ages.2 Two peaks in AHA incidence are typically observed; one associated with pregnancy, and another with older age (>60 years old). Approximately half of patients with AHA have concomitant disorders, most often other autoimmune disorders or malignancy.3,4 In approximately 1−5% of cases, AHA is diagnosed during pregnancy or within 1 year following childbirth.5 The bleeding phenotype of AHA is variable, ranging from life-threatening bleeds to
Correspondence:
ANDREAS TIEDE
tiede.andreas@mh-hannover.de
Received: June 27, 2019. Accepted: April 7, 2020. Pre-published: May 7, 2020.
doi:10.3324/haematol.2019.230771
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1791
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