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Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3623-3628 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons Dongmei Wu, Karen Vanhoorelbeke, Nancy Cauwenberghs, Muriel Meiring, Hilde Depraetere, Harry F. Kotze, and Hans Deckmyn From the Laboratory for Thrombosis Research, Interdisciplinary Research Center, K U Leuven Campus Kortrijk, Kortrijk, Belgium; and the Department of Haematology and Cell Biology, University of the Orange Free State, Bloemfontein, South Africa. The interaction between collagen, von Willebrand factor (VWF), and glycoprotein Ib is the first step in hemostasis and thrombosis especially under high shear conditions. We studied the inhibition of the VWF-collagen interaction by using an antihuman VWF monoclonal antibody 82D6A3 to prevent arterial thrombosis in baboons to develop a new kind of antithrombotic strategy and determine for the first time experimental in vivo data concerning the importance of the collagen-VWF interaction. We used a modified Folts model to study the antithrombotic efficacy of 82D6A3, where cyclic flow reductions (CFRs) were measured in the femoral artery. Administering a dose of 100, 300, and 600 µg/kg resulted in a 58.3%, 100%, and 100% reduction in the CFRs, respectively. When 100 µg/kg 82D6A3 was infused into the baboons, 80% of VWF-A3 domain was occupied, corresponding to 30% to 36% ex vivo inhibition of VWF binding to collagen, with no prolongation of the bleeding time. The bleeding time was also not significantly prolonged when the CFRs were abolished at doses of 300 µg/kg and 600 µg/kg. At these doses 100% of VWF was occupied by the antibody and 100% ex vivo inhibition of the VWF-collagen binding was observed. 82D6A3 has a high affinity for VWF; after 48 hours still 68% VWF (300µg/kg) was occupied with a pharmacologic effect up to 5 hours after administration (80%-100% occupancy). In conclusion, these results clearly indicate that the VWF-collagen interaction is important in vivo in thrombosis under high shear conditions and thus might be a new target for preventing arterial thrombosis. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: A modified Folts model or the original Folts model to evaluate new antithrombotics? Maurizio Fattorutto, Hans Deckmyn, Karen Vanhoorelbeke, and Harry Kotzé Blood 2003 101: 782. 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