How Vioxx causes thrombosis:

“Thromboxane A2, a major COX-1–mediated product of arachidonic acid metabolism, causes irreversible platelet aggregation, vasoconstriction, and smooth-muscle proliferation, whereas prostacyclin is an inhibitor of platelet aggregation, a vasodilator, and an inhibitor of smooth-muscle proliferation. COX-2 is the chief source of systemic prostacyclin synthesis, and COX-2 inhibitors may increase the cardiovascular risk by shifting the functional balance of these vasoactive eicosanoids toward the promotion of thrombosis or atherogenesis. COX-2 inhibition combined with thromboxane-receptor antagonism may also lead to the destabilization of atheromatous plaque. In addition, COX-2 plays a role in angiogenesis. How these pharmacologic observations relate to the clinical cardiovascular findings with COX-2 inhibition is unknown.” -NEJM, March 17, 2005,Cardiovascular Events Associated with Rofecoxib…