ACQUIRED HEMOPHILIA

• Published in: Reviews in clinical and experimental hematology Vol. 5; no. 4; pp. 389 - 404
• Main Authors: Boggio, Lisa N., Green, David
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2001
• Subjects: Adrenal Cortex Hormones - therapeutic use; Autoantibodies - blood; Autoantibodies - drug effects; Autoimmune Diseases - diagnosis; Autoimmune Diseases - immunology; Autoimmune Diseases - therapy; Factor VIII - immunology; Factor VIII - therapeutic use; Hemophilia A - diagnosis; Hemophilia A - immunology; Hemophilia A - therapy; Humans; Immune Tolerance - drug effects
• ISSN: 1127-0020; 1468-0734
• DOI: 10.1046/j.1468-0734.2001.00049.x

Acquired hemophilia is a serious coagulopathy usually affecting the elderly, persons with autoimmune disorders and, infrequently, women in the immediate postpartum period. It is due to autoantibodies directed against specific domains of the factor VIII molecule, leading to inhibition of factor VIII binding to von Willebrand factor, to activated factor IX or to negatively charged phospholipids. This results in bleeding into the skin, muscles, gastrointestinal and genitourinary tracts, and other sites. Mixing patient plasma with normal plasma prolongs the activated partial thromboplastin time of the normal plasma and the Bethesda assay provides a quantitative estimate of the strength of the inhibitor. The selection of therapeutic concentrates for the management of acute bleeding is related to the titer of the inhibitor; if less than 5 Bethesda Units, human factor VIII may be effective, but higher titer inhibitors usually respond only to porcine factor VIII, recombinant factor VIIa or activated prothrombin complex concentrates. Corticosteroid treatment leads to disappearance of the autoantibody in 50% of patients; cyclophosphamide and cyclosporine are effective in many who do not respond to steroids. Occasionally, high dose intravenous immunoglobulin or immunosorbent columns transiently decrease inhibitor titers and enable control of bleeding. Other autoantibodies have been described against factors V, VII, XI and, rarely, factor XIII and prothrombin. New approaches in the management of autoimmune disease and, especially, methods to establish tolerance are in development.