PHYSIOPATHOLOGICAL SIGNIFICANCE OF CATALYTIC PHOSPHOLIPIDS IN THE GENERATION OF THROMBIN

Thrombin generation is the culminating event of the coagulation cascad e, It is initiated after the expression of tissue factor by endothelia l cells and monocytes exposed to thrombogenic stimuli, Anionic phospho lipids, chiefly phosphatidylserine, are necessary for the optimal acti vity of tissue factor and completion of the clotting process, They dis play a catalytic potential by allowing the formation of the characteri stic enzyme complexes at the membrane surface, Platelets are viewed as the main source of procoagulant phospholipids referred to as platelet factor 3, The plasma membrane of resting cells presents an asymmetric al distribution of phospholipids, aminophospholipids being sequestered in the inner leaflet, Procoagulant phopholipids become available at t he outer surface after cell stimulation, The collapse of the membrane asymmetry is thought to promote a phospholipid scrambling accompanied by the shedding of microparticles. The plasma membranes of such vesicl es bear irreversibly externalized procoagulant phosphatidylserine and contain glycoproteins that testify to their tissue origin, Hence, micr oparticles could disseminate a dual procoagulant and adhesive potentia l, Thrombin autoamplification is exerted through feedback activation l oops involving either coagulation factors or platelets, This article d etails the mechanisms by which procoagulant phospholipids promote the generation of an excess of thrombin, A new pharmacological approach of thrombosis is presented, based on the control of the exposure of proc oagulant phospholipids and membrane microparticle shedding.