Study designs: To describe retrospectively the experience of the Internal Medicine and Clinical Hematology Departments of a University Hospital on adult acquired hemophilia (AH) caused by autoantibody against factor VIII coagulant (f.VIII:C) activity. Diagnosis, clinical datas, associated diseases, treatment and final outcome are described and compared to the published literature.
Material and methods: All cases admitted in both departments since 1989 were enrolled in the study. Clotting analyses comprised clotting times (activated partial thromboplastin time, prothrombin and thrombine times), measurements of f.VIII:C level, antifactor VIII detection and measurement by the Bethesda method assay, Search for an etiologic factor could not be standardized. All patients were followed until cure, sustained improvement, or death.
Results: From 1989 to 1996, AH was diagnosed in nine adult patients. Mean age was 76 +/- 24.6 years (range : 65-89) and sex ratio male to female was 2. Eight bleeding episodes occurred in seven patients, resulting consistently in severe hemorrhagic anemia and leading to hemodynamic failure in two, while two others remained asymptomatic for prolonged periods. The initial levels of f.VIII:C ranged from less than 1% to 20%, and the titers of inhibitors ranged from 0.5 to 100 Bethesda units. An underlying disease, to which the appearance of their inhibitor could be related, either concomitantly or up to 1 year later, was found in four cases including (one case each): rheumatoid arthritis, lupus erythematosus with antiphospholipid syndrome, followed by non-Hodgkin malignant lymphoma, relapsing carcinoma and, biliary tract surgery. Six acute bleeding episodes necessitated symptomatic measures, based on activated prothrombin complex concentrates in four instances, with a good response in all cases. Preparation to minor surgical operations was achieved in two asymptomatic subjects by either highly purified factor VIII concentrations infusion or intravenous 1-desamino-8-D-arginine vasopressin, with a good control of local hemostasis in each case. Three received intravenous immunoglobulins, which resulted in success in one, failure in one and, questionable response in the latter. Immunosuppression, mainly with corticosteroids, cyclophosphamid, or both, was given to seven, resulting in disappearance of inhibitor in five (delay to cure ranged from 2 weeks to 10 months), improvement in one, and failure in one (in this latter case, cure was eventually achieved with the anti-Hodgkin disease MOPP chemotherapy). After a 27-month mean follow-up, six patients experienced a sustained complete response and one a sustained partial response to immuno-suppression, two untreated patients remained asymptomatic, two died later from malignancy (carcinoma and myelodysplastic syndrome).
Conclusion: AH usually presents as a severe or even a life-threatening disease, necessitating prompt and thorough symptomatic measures directed at the cessation of bleedings and prevention of their relapse. In our experience, no death was attributable to AH or its treatment. Immunosuppression is useful in selected cases, but must be carefully discussed, since it can be highly toxic, especially in the elderly. Given the possibility of a delayed onset of some etiologic factors, a prolonged surveillance of each case of idiopathic AH is mandatory.