Review Acquired hemophilia A: Diagnosis, aetiology, clinical spectrum and treatment options Shrimati Shetty a, ⁎, Manali Bhave b , Kanjaksha Ghosh a a National Institute of Immunohematology ( ICMR), 13th Floor, KEM Hospital, Parel, Mumbai 400 012, India b Feinberg School of Medicine, Northwestern University, USA abstract article info Article history: Received 12 November 2010 Accepted 23 November 2010 Available online 27 November 2010 Keywords: Acquired hemophilia A Autoantibodies Immunosuppressive therapy Factor VIII Inhibitors Acquired hemophilia A (AHA) is a rare disorder with an incidence of approximately 1 per million/year with a high mortality rate of more than 20%. The disease occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralize its procoagulant function and result in severe, often life-threatening bleeding. The antibodies arise in individuals with no prior history of hemophilia A. AHA may be associated with pregnancy, autoimmune diseases, malignancy, infections or medication and occurs most commonly in the elderly. Approximately 50% of the patients remain idiopathic with no known underlying pathological condition. Clinical manifestations include spontaneous hemorrhages into the skin, muscles or soft tissues or excessive bleeding during surgery. Hemarthrosis which is the hallmark of congenital severe hemophilia A seldom occurs in AHA. The diagnosis of AHA is based on the isolated prolongation of activated partial thromboplastin time (APTT) which does not normalize after the addition of normal plasma along with reduced FVIII levels. The treatment involves two aspects—eradication of antibodies and maintaining effective hemostasis during a bleeding episode. The protocols for eradication of antibodies include immunoadsorption, immunosuppression or immune tolerance induction (ITI). The treatment of acute bleeding episodes involves use of different bypassing agents like recombinant activated factor VIIa (rFVIIa, NovoSeven®) and activated prothrombin complex concentrate (aPCC, (FEIBA®) in case of patients with high titer inhibitors or with antifibrinolytics,1- deamino-8-D-arginine vasopressin (DDAVP) or FVIII concentrates in low titer inhibitor patients. The anti CD20 monoclonal antibody, rituximab, has shown very good results either singly or in combination with immunosuppressive regimens in patients who do not respond to standard immunosuppressors. The present review summarizes the diagnostic, aetiological, clinical and treatment aspects of AHA focusing on the recent advances in this area. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 1.1. Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 1.2. Aetiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 1.3. Genetic basis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 1.4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 1.5. Bleeding manifestation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 2. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 2.1. Haemostatic agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 2.1.1. Recombinant factor VIIa (rFVIIa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 2.1.2. Activated prothrombin complex concentrates (aPCC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 2.1.3. 1-deamino-8-D-arginine vasopressin (DDAVP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 2.1.4. Factor VIII concentrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 3. Eradication of inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 3.1. Intravenous immunoglobulin (IVIG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 3.2. Immunoadsorption / plasmapheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 3.3. Immune tolerance induction (ITI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 Autoimmunity Reviews 10 (2011) 311–316 ⁎ Corresponding author. Tel.: + 91 22 24138518; fax: + 91 22 24138521. E-mail address: shrimatishetty@yahoo.com (S. Shetty). 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.11.005 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev