TY - JOUR
T1 - Insights into platelet-based control of coagulation
AU - de Witt, Susanne M.
AU - Verdoold, Remco
AU - Cosemans, Judith M. E. M.
AU - Heemskerk, Johan W. M.
PY - 2014/5
Y1 - 2014/5
N2 - 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 Ca2+ 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.
AB - 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 Ca2+ 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.
KW - Clot retraction
KW - Coagulation
KW - Platelets
KW - Procoagulant activity
KW - Thrombus
KW - Fibrin
U2 - 10.1016/S0049-3848(14)50024-2
DO - 10.1016/S0049-3848(14)50024-2
M3 - Article
SN - 0049-3848
VL - 133
SP - S139-S148
JO - Thrombosis Research
JF - Thrombosis Research
ER -