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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2001-12-0190.

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Blood, 1 February 2003, Vol. 101, No. 3, pp. 921-928

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation

Keith E. Norman, Matthew J. Cotter, James B. Stewart, Kate B. Abbitt, Majid Ali, Bart E. Wagner, William A. H. Wallace, S. Bradley Forlow, and Paul G. Hellewell

From the Cardiovascular Research Group, Division of Clinical Sciences (North), University of Sheffield, Sheffield, United Kingdom; Department of Histopathology, Northern General Hospital, Sheffield, United Kingdom; and Department of Biomedical Engineering, University of Virginia, Charlottesville.

Widespread microvascular injury followed by vessel obstruction may lead to disseminated intravascular coagulation (DIC). We describe a murine model wherein leukocytes interacting with inflamed microvessels in vivo are activated by antibodies. Treatment of tumor necrosis factor alpha  (TNF-alpha )-primed mice with anti-Ly-6G antibodies reproduced many of the features of septic or traumatic shock including microvessel obstruction and coagulation, severe vasculitis, respiratory difficulties, and vascular leakage. Mice lacking either E-selectin or P-selectin were protected from this reaction as were animals treated with a combination of either selectin-blocking antibodies and heparin or a selectin antagonist plus heparin. Combined blockade of leukocyte/platelet adhesion and coagulation may provide convincing protection in DIC.

© 2003 by The American Society of Hematology.
 

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