Platelet protein S limits venous but not arterial thrombosis ...

THROMBOSIS AND HEMOSTASIS| MAY 28, 2020

Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus

Sara Calzavarini, Raja Prince-Eladnani, François Saller, Luca Bologna, Laurent Burnier, Anne C. Brisset, Claudia Quarroz, Maria Desiré Reina Caro, Vladimir Ermolayev, Yasuhiro Matsumura, José A. Fernández, Tilman M. Hackeng, John H. Griffin, Anne Angelillo-Scherrer

Blood (2020) 135 (22): 1969–1982.

https://doi.org/10.1182/blood.2019003630

Key Points

PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries.

PSplt limits thrombin generation in the thrombus and ensures that highly activated platelets and fibrin remain localized at the injury site.

Abstract

Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site. In the presence of high thrombin concentrations, clots from Pros1lox/loxPf4-Cre− mice contract, but not clots from Pros1lox/loxPf4-Cre+ mice, because of highly dense fibrin networks. Thus, PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries.

Subjects:

Platelets and Thrombopoiesis, Thrombosis and Hemostasis

Topics:

blood platelets, mice, protein s, thrombin, thrombus, blood coagulation, coagulation process, fibrin, thrombosis, tissue factor pathway inhibitor

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