The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis

Abstract

The inhibition of factor VIII by autoantibody development, or acquired hemophilia, occurs in approximately one person per million each year and can cause life-threatening bleeding. Due to the disease rarity, there are no randomized studies addressing prognostic features and treatment. The goal of this study is to identify prognostic indictors in acquired hemophilia to guide treatment choices. MEDLINE and EMBASE search from 1985-2008 retrieved 32 studies with detailed clinical information on five or more patients with acquired hemophilia. Univariate and multivariate analysis of the effects of age, sex, underlying condition, inhibitor titer, and treatment regimen were evaluated with regards to complete remission and death. A total of 32 studies containing 359 patients with acquired hemophilia were included in the analysis. The all-cause mortality rate in this cohort was 21%. Multivariate analyses revealed that patients more likely to die are the elderly [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.32-4.36] and those with underlying malignancy (OR 2.76, CI 1.38-5.50). Early achievement of complete remission resulted in improved survival. Complete remission occurred in 94% of patients receiving combination chemotherapy, 82% receiving dual therapy, and 68% receiving steroids alone. Patients receiving immunosuppression had reduced odds of persistent hemophilia, with combination chemotherapy being the most efficacious (OR 0.04, CI 0.01-0.23) and steroid therapy alone being the least (OR 0.38, CI 0.14-0.94). In acquired hemophilia, increased age, underlying malignancy, and lack of complete remission are risk factors for death. Although the included studies were not randomized, patients treated with combination chemotherapy had the greatest odds of remission and the lowest odds of death.