Rituximab in the treatment of acquired factor VIII inhibitors
ABSTRACT Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth, a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation.
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ABSTRACT: The development of inhibitory antibodies to factor VIII (FVIII) or factor IX (FIX) in patients with haemophilia is a serious complication of treatment with coagulation factor concentrates. Antibodies develop in 10-15% of haemophilia A and in up to 5% of haemophilia B patients. Several strategies have been developed over the years to facilitate the eradication of inhibitors and reduce the cost. These include plasmapheresis and/or extracorporeal protein A absorption to remove the inhibitor from the plasma, and immunosuppression and/or immune modulation to suppress the production of inhibitory antibodies. Different immunosuppressive (IS) agents have been described with varying success. To evaluate the outcome of these agents, we performed a systematic literature review using the PubMed database. The total number of articles identified was 345; 299 papers were excluded leaving 46 papers to be included in the study. No randomised studies were identified, only case reports and case series. The most frequently used agents in the 46 case reports and cohort studies identified were cyclophosphamide and rituximab. All cases exposed to cyclophosphamide, rituximab and other IS agents had a complete success rate of 40-44%, 40-63% and 33-56%, respectively. However, the definition of success was not consistent among the studies. In conclusion, our review of the literature indicates that IS agents in combination with FVIII or FIX could be an option and may be cost-effective in many patients. The risk of adverse events seems to be relatively low. To fully explore the effect of IS agents, randomised studies are warranted.European journal of haematology. Supplementum 08/2014; 76:26-38. DOI:10.1111/ejh.12372
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ABSTRACT: Acquired von Willebrand syndrome (AVWS) is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE) is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT) with severely decreased levels of von Willebrand factor (VWF) measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG) and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.01/2014; 2014:208597. DOI:10.1155/2014/208597