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Roles of platelets and factor XI in the initiation of blood coagulation by thrombin.
Thromb Haemost. 2001 Jul; 86(1):75-82.TH

Abstract

To account for the variable hemostatic defect in patients with factor XI (FXI) deficiency, with normal hemostasis in contact factor deficiencies, a coagulation paradigm is presented whereby trace quantities of thrombin, generated transiently by exposure of tissue factor at sites of vascular injury, activates FXI bound to the platelet surface in the presence of prothrombin or high Mr kininogen (HK). Tissue factor pathway inhibitor (TFPI) limits the flux of thrombin generated by the tissue factor pathway, and protease nexin II (PNII), released from activated platelets, inhibits solution phase FXIa and localizes FIX activation to the platelet surface where FXIa is protected from inactivation by PNII. Either prothrombin or HK binds to the Apple 1 (A1) domain of FXI, thereby exposing a platelet-binding site in the FXI A3 domain. Dimeric FXI binds to activated platelets directly through the A3 domain of one monomer. After proteolytic activation of platelet-bound FXI by thrombin (or FXIIa), a substrate binding site for FIX is exposed in the opposite monomer that promotes FIX activation on the platelet surface resulting in the local explosive generation of thrombin and the formation of hemostatic thrombi at sites of vascular injury.

Authors+Show Affiliations

Sol Sherry Thrombosis Research Center, Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA. pnw@astro.ocis.temple.edu

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

11487044

Citation

Walsh, P N.. "Roles of Platelets and Factor XI in the Initiation of Blood Coagulation By Thrombin." Thrombosis and Haemostasis, vol. 86, no. 1, 2001, pp. 75-82.
Walsh PN. Roles of platelets and factor XI in the initiation of blood coagulation by thrombin. Thromb Haemost. 2001;86(1):75-82.
Walsh, P. N. (2001). Roles of platelets and factor XI in the initiation of blood coagulation by thrombin. Thrombosis and Haemostasis, 86(1), 75-82.
Walsh PN. Roles of Platelets and Factor XI in the Initiation of Blood Coagulation By Thrombin. Thromb Haemost. 2001;86(1):75-82. PubMed PMID: 11487044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of platelets and factor XI in the initiation of blood coagulation by thrombin. A1 - Walsh,P N, PY - 2001/8/7/pubmed PY - 2002/1/23/medline PY - 2001/8/7/entrez SP - 75 EP - 82 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 86 IS - 1 N2 - To account for the variable hemostatic defect in patients with factor XI (FXI) deficiency, with normal hemostasis in contact factor deficiencies, a coagulation paradigm is presented whereby trace quantities of thrombin, generated transiently by exposure of tissue factor at sites of vascular injury, activates FXI bound to the platelet surface in the presence of prothrombin or high Mr kininogen (HK). Tissue factor pathway inhibitor (TFPI) limits the flux of thrombin generated by the tissue factor pathway, and protease nexin II (PNII), released from activated platelets, inhibits solution phase FXIa and localizes FIX activation to the platelet surface where FXIa is protected from inactivation by PNII. Either prothrombin or HK binds to the Apple 1 (A1) domain of FXI, thereby exposing a platelet-binding site in the FXI A3 domain. Dimeric FXI binds to activated platelets directly through the A3 domain of one monomer. After proteolytic activation of platelet-bound FXI by thrombin (or FXIIa), a substrate binding site for FIX is exposed in the opposite monomer that promotes FIX activation on the platelet surface resulting in the local explosive generation of thrombin and the formation of hemostatic thrombi at sites of vascular injury. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/11487044/Roles_of_platelets_and_factor_XI_in_the_initiation_of_blood_coagulation_by_thrombin_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11487044.ui DB - PRIME DP - Unbound Medicine ER -
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