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Blood, 1 January 2006, Vol. 107, No. 1, pp. 46-51. Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-04-1371. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1371v1 107/1/46    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goudemand, J. Articles by Calvez, T. Search for Related Content PubMed PubMed Citation Articles by Goudemand, J. Articles by Calvez, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Free Research Articles Clinical Trials and Observations Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A Jenny Goudemand, Chantal Rothschild, Virginie Demiguel, Christine Vinciguerrat, Thierry Lambert, Hervé Chambost, Annie Borel-Derlon, Ségolène Claeyssens, Yves Laurian, Thierry Calvez, the members of the FVIII-LFB and Recombinant FVIII study groups From the Hemophilia Treatment Center (HTC) of University of Lille2, Lille; HTC Paris Assistance Publique–Hôpitaux de Paris (AP-HP) Hôpital Necker; Institut National de la Santé et de la Recherche Médicale (INSERM) U 720, Paris; Haematology Department, Hôpital Edouard Herriot, Lyon; HTC Paris AP-HP Hôpital Bicêtre; HTC Hôpital de la Timone, Marseille; HTC Hôpital Côte de Nacre, Caen; HTC Hôpital Purpan, Toulouse; Medical University Paris XIII; and INSERM U 689, Paris, France. Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII). In addition to the usual end points (all inhibitors, high inhibitors), we also examined a third end point (high inhibitors and/or immune tolerance induction). The risk of inhibitor development was higher in patients treated with rFVIII than in patients treated with pFVIII, regardless of other risk factors (F8 genotype; nonwhite origin; history of inhibitors in patients with a family history of hemophilia; age at first FVIII infusion). The adjusted relative risk (RRa) for inhibitor development with rFVIII versus pFVIII was 2.4 (all inhibitors), 2.6 (high inhibitors), and 3.2 (high inhibitors and/or immune tolerance induction), respectively, depending on the end point (above). The pathophysiology of this large effect must be understood in order to improve the characteristics of recombinant products and to reduce the incidence of inhibitors to FVIII. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Factor VIII: purer is not necessarily better Edward G. D. Tuddenham Blood 2006 107: 4-5. [Full Text] [PDF] Related Letter in Blood Online: Assessing the risk of inhibitor formation with different factor VIII products Pier M. Mannucci, Jenny Goudemand, Chantal Rothschild, Yves Laurian, and Thierry Calvez Blood 2006 107: 3809-3810. [Full Text] [PDF] This article has been cited by other articles: K. R. Viel, A. Ameri, T. C. Abshire, R. V. Iyer, R. G. Watts, C. Lutcher, C. Channell, S. A. Cole, K. M. Fernstrom, S. Nakaya, et al. Inhibitors of Factor VIII in Black Patients with Hemophilia N. Engl. J. Med., April 16, 2009; 360(16): 1618 - 1627. [Abstract] [Full Text] [PDF] J. Krudysz-Amblo, B. Parhami-Seren, S. Butenas, K. E. Brummel-Ziedins, E. D. Gomperts, G. E. Rivard, and K. G. Mann Quantitation of anti-factor VIII antibodies in human plasma Blood, March 12, 2009; 113(11): 2587 - 2594. [Abstract] [Full Text] [PDF] C. L. Kempton and G. C. White II How we treat a hemophilia A patient with a factor VIII inhibitor Blood, January 1, 2009; 113(1): 11 - 17. [Abstract] [Full Text] [PDF] S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF] A. Gringeri and P. M. 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VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors Blood, January 15, 2007; 109(2): 610 - 612. [Abstract] [Full Text] [PDF] P. M. Mannucci, J. Goudemand, C. Rothschild, Y. Laurian, and T. Calvez Assessing the risk of inhibitor formation with different factor VIII products. Blood, May 1, 2006; 107(9): 3809 - 3810. [Full Text] [PDF] D. Lillicrap The Role of Immunomodulation in the Management of Factor VIII Inhibitors Hematology, January 1, 2006; 2006(1): 421 - 425. [Abstract] [Full Text] [PDF]

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