Immunoadsorption for the Treatment of Acquired Haemophilia: A Systematic Review

Background: Acquired haemophilia is a very rare autoimmune disease with a high risk of severe haemorrhagic complications and even death. Randomized controlled trials studying the treatment are however not available and the optimal treatment is unclear. Immunoadsorption removing the autoantibodies against factor VIII is suggested and occasionally applied in addition to immunosuppressive treatment; the efficacy is however unknown.

Aim: We aimed to systematically search and retrieve all publications reporting on immunoadsorption for the treatment of acquired haemophilia and summarize the available data on efficacy.

Methods: We developed a search strategy for Medline and EMBASE database. Inclusion criteria were (1) patients with acquired haemophilia, (2) treatment with immunoadsorption, and (3) available laboratory and clinical outcomes. Two reviewers (M.P. and M.N.) assessed eligibility and retrieved data. We extracted the following data: author, year of publication, number of patients including age, sex, activated partial thromboplastin time (aPTT), factor VIII (FVIIl) before and after the therapy, inhibitor titer, number of immunoadsorption cycles, co-treatment, remission status, bleeding complications and deaths.

Results: After de-duplication, we screened 420 hits, assessed 52 articles in full-text and included 12 studies reporting on 172 patients. The study design was a retrospective case series in most publications. Patients age varied from 14 to 94 years. Forty-five percent of the patients were female. Inhibitor titer was above 5 BU/ml in most patients and many of them experienced ongoing bleeding episodes despite initial treatment. A variety of immunoadsorption columns were used and the median number of cycles ranged between 2 and 24. Co-treatment included high-dose steroids, recombinant activated factor VII, cyclophosphamide, other coagulation factors and immunosuppressive drugs. A complete remission, as defined as a recovery of FVIII >70%, was achieved in 125 patients (73%) and a partial remission (recovery of FVIII >30%) in 6 patients (3%). Forty-four patients (26%) did not respond and 45 patients (25%) died.

Conclusions: The present data suggests, that immunoadsorption, in combination with bypassing agents and immunosuppressive treatment, is associated with a clinical and laboratory response of acquired haemophilia in a majority of cases. Future research shall identify the patients benefiting most from immunoadsorption.