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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
 (TNF-)-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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