Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation |
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Authors: | Norman Keith E Cotter Matthew J Stewart James B Abbitt Kate B Ali Majid Wagner Bart E Wallace William A H Forlow S Bradley Hellewell Paul G |
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Affiliation: | Cardiovascular Research Group, Division of Clinical Sciences (North), University of Sheffield, Sheffield, United Kingdom. k.norman@shef.ac.uk |
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Abstract: | 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. |
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