© 2006 Schattauer GmbH, Stuttgart 119 The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders Massimo Franchini 1 , DinoVeneri 2 ,Giuseppe Lippi 3 , Rachel Stenner 4 1 Servizio di Immunoematologia eTrasfusione – Centro Emofilia, Azienda Ospedaliera diVerona,Verona; 2 Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università diVerona,Verona, Italy; 3 Istituto di Chimica e Microscopia Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università diVerona, 4 New Hall, University of Cambridge, Cambridge, UK Summary Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells which has proven to be ef- fective in the therapy of CD-20 positive lymphomas.Its B-cell cy- totoxic action has also been exploited in many non-malignant autoimmune disorders in which it has been used with the aim of interfering with the production of pathologic antibodies. The present knowledge regarding the use of rituximab in antibody- associated disorders of hemostasis (i.e.idiopathic thrombocyto- penic purpura,thrombotic thrombocytopenic purpura,acquired Keywords Rituximab, inhibitor, coagulation disorders hemophilia A, congenital hemophilia with inhibitors, acquired in- hibitors against coagulation factors) is presented briefly in this review.The results suggest that rituximab can be useful in the treatment of disorders of hemostasis associated with inhibitor formation.Although collectively the number of patients treated is now quite substantial, most of the data are drawn from iso- lated case reports or descriptions of small, uncontrolled series. Large, prospective, randomized trials are, therefore, needed to confirm the positive, preliminary results. Thromb Haemost 2006; 96: 119–25 Review Article Correspondence to: Dr. Massimo Franchini Servizio di Immunoematologia eTrasfusione – Centro Emofilia Ospedale Policlinico, Piazzale L. Scuro, 10 37134Verona, Italy Tel.: +39 045 8074321, Fax: +39 045 8074626 E-mail: mfranchini@univr.it Received June 8, 2006 Accepted after minor revision June 23, 2006 Prepublished online July 19, 2006 doi:10.1160/TH06–06–0317 Introduction Rituximab is a chimeric monoclonal antibody against CD20, a transmembrane protein present on the surface of essentially all B cells but not on mature plasma cells.This monoclonal antibody, which depletes B cells in the circulation and lymphoid tissues, has demonstrated efficacy in the treatment of CD20-positive lymphoproliferative disorders (1). Recent preliminary studies have indicated that this agent may also be effective in a number of autoantibody-mediated diseases such as thrombotic thrombocy- topenic purpura (2), systemic lupus erythematosus (3), rheuma- toid arthritis (4), autoimmune hemolytic anemia (5–7), cryoglo- bulin disease (8, 9), acquired factor VIII antibodies (10), IgM polyneuropathies (11), glomerulonephropathies (12), and im- mune thrombocytopenic purpura (ITP) (13). Rituximab has also been used with success to induce immune tolerance in congenital hemophiliacs with alloantibodies against factor VIII and IX (14). Based on a literature search, including PubMed, references from reviews and abstracts from the most important meetings on this topic, we present an overview of the current knowledge on ri- tuximab therapy in disorders of hemostasis associated with in- hibitor development. Rituximab for the treatment of immune thrombocytopenic purpura There are several reports on the successful use of rituximab, at the same dosage as that used for the treatment of lymphoma (375 mg/m 2 weekly for four weeks intravenously), as second-line therapy for patients with ITP (15–36). However, most of these are only anecdotal case reports. The first study involving a con- sistent number of patients was published in 2001 by Stasi and colleagues (19), who treated 25 patients with ITP resistant to two to five other therapeutic options with rituximab 375 mg/m 2 weekly for four weeks. Five patients showed a complete response and five others had a partial response. In seven of these patients the responses were sustained for over six months. However, in two patients with relapsed disease, repeat treatment with rituxi- mab induced a new response. There was a suggestion that younger patients were more likely to respond. Interestingly, in a subsequent report of another seven cases (20), the authors identi- fied two patterns of response: an early response in which the pla- telet count increase was seen after the first or second antibody in- fusion and a late response in which the rise in the platelet count was not observed during rituximab administration but only at For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.thrombosis-online.com on 2018-05-13 | ID: 1001066444 | IP: 54.70.40.11