DEFECTS IN HEMOSTASIS IN P-SELECTIN-DEFICIENT MICE

Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et al, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin-deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of t he tail. Moreover, defective hemostasis was observed in a local Shwart zman-like reaction induced by skin injections of lipopolysaccharide fo llowed by tumor necrosis factor-alpha in the P-selectin-deficient mice . The hemorrhagic lesions, quantitated both macroscopically and micros copically, were twofold larger in the P-selectin-deficient mice. This was also confirmed by measuring the radioactivity in the skin using ch romium-labeled red blood cells, Therefore, it is evident that P-select in plays a role in hemostasis as suggested by its support of platelet rolling. (C) 1996 by The American Society of Hematology.