On the coagulation of platelet-rich plasma. Physiological mechanism and pharmacological consequences.
Thrombin formation and blood platelet reactions are intimately linked in haemostasis and in thrombosis. In vivo, procoagulant phospholipids required for the coagulation mechanism are mainly provided by activated platelets, and thrombin is the most potent platelet activator. To study these interactions, an ancient tool of coagulation physiology, the thrombin generation test, was revived and the results obtained were reviewed. The amount of thrombin activity that develops, expressed as the endogenous thrombin potential (the area under the thrombin generation curve), is influenced by the clotting factors (except XII and XIII), the activated protein C system and natural inhibitors on the one hand and by platelet activity on the other. The platelet reactions that we found to be involved are induced by thrombin via glycoprotein (GP) IIb/IIIa activation and by fibrin via interaction with GPIb. von Willebrand factor is crucial in both reactions and therefore an obligatory factor for normal thrombin generation in the presence of platelets. All antithrombotics, be it anticoagulants (e.g. OAC, all heparins or hirudin) or antiplatelet drugs (aspirin, GPIIb/IIIa blockers) diminish thrombin generation.
Béguin
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Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands.
Keularts
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D000818:Animals; D000991:Antithrombins / Q000502:physiology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000502:physiology; D005337:Fibrin / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D010743:Phospholipids / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D013915:Thrombasthenia / Q000097:blood; D013917:Thrombin / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000502:physiology
D000991:Antithrombins; D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D010743:Phospholipids; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005337:Fibrin; D013917:Thrombin