[Prostanoids and hemostasis]

Thromboxane A2 (TXA2) and prostacyclin (two prostanoids) are produced from arachidonic acid through the cycloxygenase pathway. The enzyme cyclooxygenase is inhibited by aspirin. Prostanoids are short-lived and thus exert their effects locally. Activated platelets synthetize TXA2 which reinforces activation of those platelets and platelets in the vicinity of the former. Complete activation however can occur in the absence of TXA2 synthesis. Prostacyclin is able to block all the platelet responses, but this would be achieved in vivo together with intense vasodilation. Primary adhesion remains unaffected, since it does not require platelet activation. There are other molecules endowed with inhibitory effects on platelets: PGD2, PGE1, adenosine, and EDRF (nitric oxide). These molecules, and prostacyclin, also have effects on other cells than platelets and smooth muscle cells: leukocytes, endothelial cells. Clinical investigations on the prostanoid system in physiology and pathology of the cardiovascular system have been hampered by analytical problems. Taking into account all these restrictions, a rational pharmacological approach is difficult, but newer molecules with dual and selective activity against TXA2 (both inhibitor of TX-synthetase and antagonist at the TXA2-receptor level) seem promising as anti-thrombotic agents.