title: Acquired haemophilia A. First line treatment with calcineurin inhibitors and steroid pulses: a 10-year follow-up study.
abstract: Acquired haemophilia A (AH) is defined as the presence of autoantibodies or inhibitors against factor VIII (FVIII) with a clinical bleeding onset that can be life-threatening. Immunosuppressant therapy must be initiated rapidly to eradicate the inhibitor. Current treatments based on steroids plus cyclophosphamide or rituximab are quite effective, but with significant side-effects. Based on previous described AH cases treated with cyclosporine, with a good side-effect profile, we aimed at assessing prospectively a first-line calcineurin inhibitor based immunosuppressive therapy. We included a total of 11 patients affected with AH. Once diagnosed, pulse steroids and calcineurin inhibitors were started. Time to achieve sustained response (SR), defined as testing negative for inhibitor and with stable FVIII level >50%, immunosuppressant side-effects, and relapse of AH were evaluated. Eight patients received cyclosporine and three patients received tacrolimus. SR was achieved in 10 of 11 patients (90.9%) in a median time of 3 weeks (range 2-8 weeks), and none of them relapsed during a median follow-up time of 14 months (range 4-120). One major side-effect appeared (posterior encephalopathy) that forced to discontinue cyclosporine. Overall 5-year survival rate was 54.5%, with a total of five patients dying during the follow-up (mortality rate of 45.5%). These five patients had achieved SR and died because of complications of basal morbidities and/or senescence, not related to AH (bleeding) or to immunosuppressant's (infection) side-effects. Combination therapy of calcineurin inhibitors and pulse steroids seems clinically effective as a first-line treatment of AH.
authors.affiliation: Department of Internal Medicine, Vall d'Hebrón University General Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain. jpardosgea@yahoo.es
authors.forename: J
authors.initials: J
authors.lastname: Pardos-Gea
authors.forename: C
authors.initials: C
authors.lastname: Altisent
authors.forename: R
authors.initials: R
authors.lastname: Parra
authors.forename: M
authors.initials: M
authors.lastname: Vilardell-Tarrès
authors.forename: J
authors.initials: J
authors.lastname: Ordi-Ros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000276:immunology; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D013256:Steroids / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D019774:Blood Coagulation Factor Inhibitors; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D005169:Factor VIII; D016559:Tacrolimus