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

Calzavarini, Sara; Prince-Eladnani, Raja; Saller, François; Bologna, Luca; Burnier, Laurent; Brisset, Anne C; Quarroz, Claudia; Reina Caro, Maria Desiré; Ermolayev, Vladimir; Matsumura, Yasuhiro; Fernández, José A; Hackeng, Tilman M; Griffin, John H; Angelillo-Scherrer, Anne (2020). Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus. Blood, 135(22), pp. 1969-1982. American Society of Hematology 10.1182/blood.2019003630

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Calzavarini, Sara; Prince Eladnani, Raja; Bologna, Luca; Quarroz, Claudia; Reina Caro, Maria Desiré and Angelillo, Anne

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

15 Jun 2020 11:19

Last Modified:

15 Jun 2020 11:19

Publisher DOI:

10.1182/blood.2019003630

PubMed ID:

32276277

BORIS DOI:

10.7892/boris.144473

URI:

https://boris.unibe.ch/id/eprint/144473

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