@article{ada9d0a376674b5492c147d775bf9333,
title = "Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus",
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 (Pros1(lox/lox)Pf4-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 Pros1(lox/lox)Pf4-Cre2(-) mice contract, but not clots from Pros1(lox/lox)Pf4-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.",
keywords = "RETROSPECTIVE FAMILY COHORT, C4B-BINDING PROTEIN, C ANTICOAGULANT, FACTOR-V, RISK, PLASMA, DEFICIENCY, THROMBOPHILIA, INDIVIDUALS, INHIBITION",
author = "Sara Calzavarini and Raja Prince-Eladnani and Francois Saller and Luca Bologna and Laurent Burnier and Brisset, {Anne C.} and Claudia Quarroz and Caro, {Maria Desire Reina} and Vladimir Ermolayev and Yasuhiro Matsumura and Fernandez, {Jose A.} and Hackeng, {Tilman M.} and Griffin, {John H.} and Anne Angelillo-Scherrer",
note = "Funding Information: This work was supported by the Swiss National Foundation for Scientific Research grants PPOOB-106690/1, PPOOP3-123430, 310030_153436, 314730_173127, and 316030_177126; the Pierre Mercier pour la Science Foundation; the CSL‐Behring‐Prof. Heimburger Award; the Bayer Hemophilia Award; La Fondation Dinu Lipatti–Dr Henri Dubois-Ferri{\`e}re; the Novartis Foundation for Medical-Biological Research (A.A.-S.); and National Institutes of Health, National Heart, Lung, and Blood Institute grants RO1 HL133728 and HL142975 (J.H.G.). Funding Information: The authors thank Haenni Beat and Helga Maria Mogel (Microscopy Imaging Center of the University of Bern) for the electron microscopy sample preparation and imaging; Jos{\'e} A. Galv{\'a}n Hern{\'a}ndez, Patricia Ney, and Irene Centos-Ramos (Translational Research Unit Platform of the University of Bern) for the microscopy sample preparation and immunohistochemistry; Denise Stalder Zeerleder (Center for Laboratory Medicine, Inselspital, Bern University Hospital) for the support for the flow cytometric analysis; Jens Stein and Neda Haghayegh (Microscopy Imaging Center of the University of Bern) for the support for the intravital microscopy experiments; David Ginsburg (University of Michigan) for providing the antibody against murine factor V; and Monica Azevedo and Beatrice Ternon for technical support. Publisher Copyright: {\textcopyright} 2020 by The American Society of Hematology",
year = "2020",
month = may,
day = "28",
doi = "10.1182/blood.2019003630",
language = "English",
volume = "135",
pages = "1969--1982",
journal = "Blood",
issn = "0006-4971",
publisher = "The American Society of Hematology",
number = "22",
}