title: Acquired haemophilia: management of bleeds and immune therapy to eradicate autoantibodies.
abstract: Acquired haemophilia is a rare, but often severe bleeding disorder caused by autoantibodies against a coagulation factor, usually factor VIII (FVIII). Between 1997 and 2004 we observed 14 patients (mean age of 78 years) with acquired haemophilia. The aim of the present study was to investigate the effect of activated prothrombin complex concentrate (aPCC) for bleeds and the response to corticosteroids and cyclophosphamide to eradicate the offending autoantibodies. The most common clinical presentations were severe profuse bruising (12) and haematuria (5). Ten patients were classified as idiopathic. At the time of diagnosis all patients had a very low FVIII level, and one patient also showed factor IX < 1%. High levels of antibodies to FVIII varying from 10 to 1340 Bethesda units (BU) and prolonged activated partial thromboplastin time were disclosed in all patients. Eight severe bleeds were treated with aPCC (FEIBA) at a dosage of 70 IU kg(-1) every 8 h until haemostasis. Ten patients received corticosteroids and cyclophosphamide as immunomodulatory therapy. Effective haemostasis was achieved in all bleeds after aPCC. Ten of 11 patients responded either completely or partially to the immunomodulatory regime within 6 months. Five patients achieved complete response (CR) whereas partial responses were seen in five patients. The anti-CD20 monoclonal antibody rituximab was given to two patients in conventional doses and a CR was seen in one patient. aPCC is effective in treating acute bleeds in patients with acquired haemophilia with high inhibitor levels. The combination of oral corticosteroids and cyclophosphamide seems to be effective to eradicate the inhibitor.
authors.affiliation: Section of Hematology, Medical Department, Rikshospitalet University Hospital, Oslo, Norway. holme@rikshospitalet.no
authors.forename: P A
authors.initials: PA
authors.lastname: Holme
authors.forename: F
authors.initials: F
authors.lastname: Brosstad
authors.forename: G E
authors.initials: GE
authors.lastname: Tjønnfjord
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005164:Factor IX / Q000032:analysis / Q000276:immunology; D005167:Factor VII / Q000627:therapeutic use; D005169:Factor VIII / Q000032:analysis / Q000276:immunology; D015942:Factor VIIa; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX; C103587:recombinant FVIIa; D015942:Factor VIIa