Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis

The growth arrest-specific gene 6 product (Gas6) is a secreted protein rela ted to the anticoagulant protein S but its role in hemostasis is unknown. H ere we show that inactivation of the Gas6 gene prevented venous and arteria l thrombosis in mice, and protected against fatal collagen/epinephrine-indu ced thrombo embolism. Gas6(-/-) mice did not, however, suffer spontaneous b leeding and had normal bleeding after tail clipping. In addition, we found that Gas6 antibodies inhibited platelet aggregation in vitro and protected mice against fatal thrombo embolism without causing bleeding in vivo. Gas6 amplified platelet aggregation and secretion in response to known agonists. Platelet dysfunction in Gas6(-/-) mice resembled that of patients with pla telet signaling transduction defects. Thus, Gas6 is a platelet-response amp lifier that plays a significant role in thrombosis. These findings warrant further evaluation of the possible therapeutic use of Gas6 inhibition for p revention of thrombosis.