title: Insights into platelet-based control of coagulation.
abstract: The coagulation process is activated by tight control mechanisms, in which platelets play prominent and unique roles. In thrombosis and hemostasis, activated platelets regulate the coagulation system in various ways: by exposing a phosphatidylserine surface for thrombin formation, by supporting fibrin formation, and by regulating the retraction of a fibrin clot. In this review we discuss the involvement of platelet receptors, other membrane proteins, downstream signaling proteins, cytoskeleton-linked proteins and plasma proteins in these procoagulant functions. Studies with both genetically modified mice and pharmacological inhibitors indicate that, for collagen-adhered platelets, in part common signaling pathways lead to phosphatidylserine exposure, generation of thrombin and fibrin, and retraction of the fibrin clot. However, prolonged Ca(2+) elevation leads to thrombin generation, whereas integrin-dependent signaling stimulates fibrin clot retraction. Contact-dependent signaling pathways, triggered by homotypic platelet-platelet interactions, act in particular via the integrin route.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: de Witt
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: Verdoold
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: judith.cosemans@maastrichtuniversity.nl.
authors.forename: Judith M E M
authors.initials: JM
authors.lastname: Cosemans
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: jwm.heemskerk@maastrichtuniversity.nl.
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D013927:Thrombosis / Q000097:blood*
chemical_list: D005337:Fibrin
keywords: Clot retraction; Coagulation; Fibrin; Platelets; Procoagulant activity; Thrombus