Wiestner, A. et al. Rituximab in the treatment of acquired factor VIII inhibitors. Blood 100, 3426-3428

Cornell University, Итак, New York, United States
Blood (Impact Factor: 10.45). 12/2002; 100(9):3426-8. DOI: 10.1182/blood-2002-03-0765
Source: PubMed


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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    • "Wiestner et al. reported successful treatment of three patients with high-titer FVIII antibodies who received up to four weekly infusions of rituximab, 375 mg/m2 and demonstrated rapid clinical improvement. Another study by Stasi et al. included 10 patients, eight patients achieved complete remission and two did not respond to rituximab (15, 16). Even though, rituximab has been reported to be an effective treatment of AHA in most case reports and small case series, it should be considered as second-line therapy in patients who fail to respond to first-line treatment. "
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    ABSTRACT: Acquired hemophilia A is a rare bleeding disorder with a high mortality rate. Diagnosis and treatment of this disorder can be very challenging to anesthesiologists because of lack of a personal or familial abnormal bleeding history. We report a 60-year-old woman who presented to the operating room for an urgent fasciotomy. She was initially diagnosed to have compartment syndrome of her left upper extremity secondary to an expanding hematoma after multiple unsuccessful venipuncture attempts. After surgical intervention, she developed recurrent intramuscular hematomas, became severely anemic, and required surgical re-exploration and multiple blood product transfusions. Ultimately, she was found to have an elevated activated partial thromboplastin time (aPTT), very low FVIII activity, and high FVIII inhibitor titers consistent with the diagnosis of acquired hemophilia A. Treatment strategies in acquired hemophilia are based on two major objectives. During the acute stage, effective control of bleeding is critical. The ultimate therapeutic goal during the subacute phase is the elimination of the inhibitors targeting factor VIII. Here, we present this case and will review current literature regarding therapeutic approaches to this rare condition in the operating room setting and postoperative course.
    Anesthesiology and Pain Medicine 02/2014; 4(1):e11906. DOI:10.5812/aapm.11906
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    • "Published case reports document the efficacy of RTX in the treatment of refractory FVIII inhibitors [1, 9, 10]. Wiestner et al. treated 4 consecutive patients with acquired FVIII inhibitor with RTX: 3 in combination with corticosteroids and one with RTX as monotherapy. "
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    ABSTRACT: This case report describes a patient with an idiopathic acquired Factor VIII inhibitor and severe bleeding. She was treated with rituximab after failing first-line treatment with steroids and cyclophosphamide. Two months following rituximab treatment, our patient developed a succession of severe opportunistic infections requiring intensive care unit admission. Over a period of 12 weeks she required treatment for Pseudomonas aeruginosa septicaemia, herpes simplex gingivostomatitis and pharyngotonsillitis, clostridium difficile-related diarrhoea, systemic cytomegalovirus infection, pneumocystis jiroveci, and invasive pulmonary aspergillosis lung infections. After significant rehabilitation, the patient was finally discharged following a 5-month admission. This case highlights the complexity of balancing a life-threatening condition with the side effects of treatment. It also raises the issue of routine prophylaxis for immunosuppression in nonmalignant conditions, which will become a common dilemma with the expanding indications for rituximab use.
    12/2013; 2013(3):703027. DOI:10.1155/2013/703027
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    • "Paleyanda and colleagues were transferred FVIII cDNA into pig lactate system; the pig was produced FVIII more than 10 times as normal plasma (Paleyanda et al., 1997). Specific thrombin anticoagulant Bivalirudin (Krolick, 2005) and monoclonal antibody Retoximab (Franchini, 2007; Wiestner et al., 2002) are also used for hemophilia treatment and patients with FVIII autoantibody, respectively. Idiotype vaccines will neutralize anti human FVIII antibody in hemophilia A patients (Lacroix-Desmazes et al., 2002). "

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