title: Current perspectives in the treatment of thrombotic disorders.
abstract: New trends in antithrombotic therapy should reside in a better adaptation, both in potency and in target to the involved thrombogenic mechanism. Thrombogenesis as hemostasis is the result of cooperation between plasma coagulation factors and platelet functions, and these two systems are themselves in equilibrated antagonism with the vessel wall, mainly endothelial cells. These triangular relations between coagulation factors, platelet functions, and endothelial cell reactivity are quantitatively regulated by flow conditions. The relative importance of each of these protagonists in the genesis of vascular thrombosis varies along the vascular tree, mainly due to changes in flow characteristics, and explain the usual separation between venous and arterial thrombosis: venous thrombosis involves mainly coagulation factors and the vascular fibrinolytic response whereas arterial thrombosis involves the thromboresistant characteristics of the endothelial cell membrane and platelet functions. The real blood flow characteristics may be altered by local disease and influences the relative involvement of coagulation and fibrinolytic factors, platelet functions, and endothelial cells. Prevention of thrombosis must take into account all these phenomena and must be targeted to the predominant factor or factors. Depending on the local conditions, the therapeutical goal can be: (1) limitation of platelet functions or coagulation factors; (2) stimulation of thromboresistant properties of the endothelium (mainly its profibrinolytic characteristics); and (3) modification of the flow conditions. Several targets can be associated: the level of inhibition or stimulation of a function depends on the dysequilibrium, and efficient prevention does not always require complete inhibition of a function. Once a thrombus has developed, antithrombotic treatment will prevent its extension, and thrombolytic therapy will try to restore vascular patency. Once patency has been restored antithrombotic therapy is still needed to prevent recurrence of the thrombus. Even if the main targeting is on platelets, the choice in the molecule to be clinically used must be defined by the function of the platelet involved: thrombogenesis or vasospasm, and even by the metabolic pathway predominantly activated. In coagulation strategy, differences must be drawn between antithrombotic therapy directed against thrombin formation, complexes of coagulation, free enzymes or activation phases. In thrombolytic therapy all procedural uses of extrinsic thrombolytic agents (natural, modified, or artificial), increase of susceptibility to endogenous thrombolytic systems, and stimulation of endogenous thrombolytic activity do not bear the same efficiency. As a consequence, the responsibility for clinical use of new molecules with more specific activity can allow more efficient antithrombotic therapy directed at the condition of an indication targeted at the exact mechanisms involved.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Hôpital Saint-Louis, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Drouet
authors.forename: J P
authors.initials: JP
authors.lastname: Caen
mesh_terms: D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D013924:Thrombophlebitis / Q000188:drug therapy; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014812:Vitamin K; D006493:Heparin