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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2001, Vol. 98, No. 8, pp. 2442-2447 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcRIIA Michael P. Reilly, Scott M. Taylor, Nealie K. Hartman, Gowthami M. Arepally, Bruce S. Sachais, Douglas B. Cines, Mortimer Poncz, and Steven E. McKenzie From the Cardeza Foundation for Hematologic Research, Departments of Medicine and Pediatrics, Jefferson Medical College; and the Departments of Pathology and Laboratory Medicine, and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia; and the Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque. Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, life-threatening complication that occurs in 1% to 3% of patients exposed to heparin. Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the hPF4/heparin complex, and the platelet Fc receptor (FcR) for immunoglobulin G, FcRIIA, are the proposed primary determinants of the disease on the basis of in vitro studies. The goal of this study was to create a mouse model that recapitulates the disease process in humans in order to understand the factors that predispose some patients to develop thrombocytopenia and thrombosis and to investigate new therapeutic approaches. Mice that express both human platelet FcRIIA and hPF4 were generated. The FcRIIA/hPF4 mice and controls, transgenic for either FcRIIA or hPF4, were injected with KKO, a mouse monoclonal antibody specific for hPF4/heparin complexes, and then received heparin (20 U/d). Nadir platelet counts for KKO/heparin-treated FcRIIA/hPF4 mice were 80% below baseline values, significantly different (P < .001) from similarly treated controls. FcRIIA/hPF4 mice injected with KKO and 50 U/d heparin developed shock and showed fibrin-rich thrombi in multiple organs, including thrombosis in the pulmonary vasculature. This is the first mouse model of HIT to recapitulate the salient features of the human disease and demonstrates that FcRIIA and hPF4 are both necessary and sufficient to replicate HIT/HITT in an animal model. This model should facilitate the identification of factors that modulate disease expression and the testing of novel therapeutic interventions. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Schneider and H. S. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020