Coagulation Factor XI Promotes Distal Platelet Activation and Single Platelet Consumption in the Bloodstream Under Shear Flow

Arteriosclerosis, Thrombosis, and Vascular Biology
Jevgenia Zilberman-RudenkoOwen J T McCarty

Abstract

Coagulation factor XI (FXI) has been shown to contribute to thrombus formation on collagen or tissue factor-coated surfaces in vitro and in vivo by enhancing thrombin generation. Whether the role of the intrinsic pathway of coagulation is restricted to the local site of thrombus formation is unknown. This study was aimed to determine whether FXI could promote both proximal and distal platelet activation and aggregate formation in the bloodstream. Pharmacological blockade of FXI activation or thrombin activity in blood did not affect local platelet adhesion, yet reduced local platelet aggregation, thrombin localization, and fibrin formation on immobilized collagen and tissue factor under shear flow, ex vivo. Downstream of the thrombus formed on immobilized collagen or collagen and 10 pmol/L tissue factor, platelet CD62P expression, microaggregate formation, and progressive platelet consumption were significantly reduced in the presence of FXI function-blocking antibodies or a thrombin inhibitor in a shear rate- and time-dependent manner. In a non-human primate model of thrombus formation, we found that inhibition of FXI reduced single platelet consumption in the bloodstream distal to a site of thrombus formation. This study demo...Continue Reading

References

Sep 2, 1991·Science·D Gailani, G J Broze
Mar 9, 2000·The New England Journal of Medicine·J C MeijersF R Rosendaal
Oct 3, 2003·Journal of Thrombosis and Haemostasis : JTH·G LavigneJ-C Gris
Oct 28, 2004·Thrombosis Research·Robert K Andrews, Michael C Berndt
Mar 29, 2007·Journal of Thrombosis and Haemostasis : JTH·D Gailani, T Renné
Jul 4, 2007·Expert Review of Cardiovascular Therapy·Thomas Renné, David Gailani
Aug 16, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Feng ShenRustem F Ismagilov
Apr 9, 2009·Blood·Dmitri V KravtsovDavid Gailani
Aug 8, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Tara C White-AdamsOwen J T McCarty
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Coen MaasRolf T Urbanus
May 12, 2010·Journal of Thrombosis and Haemostasis : JTH·M F WhelihanK G Mann
Dec 31, 2011·Journal of Biomechanical Engineering·Jennifer K W Chesnutt, Hai-Chao Han
May 7, 2013·Annual Review of Biomedical Engineering·Thomas V ColaceScott L Diamond
Oct 1, 2013·Biomedical Microdevices·Lauren D C Casa, David N Ku
Oct 25, 2013·Journal of Thrombosis and Haemostasis : JTH·A MatafonovD Gailani
Dec 9, 2014·The New England Journal of Medicine·Harry R BüllerUNKNOWN FXI-ASO TKA Investigators

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Citations

Mar 31, 2017·Platelets·Magdolna NagyFrauke Swieringa
Feb 7, 2017·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Max I BogoradPeter C Searson
Feb 24, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Sravya KattulaAlisa S Wolberg
Jul 10, 2019·Stroke; a Journal of Cerebral Circulation·Hendrikus J A van OsBob S Siegerink
Jun 6, 2017·Cellular and Molecular Bioengineering·Jevgenia Zilberman-RudenkoJeevan Maddala
Jan 14, 2017·Cellular and Molecular Bioengineering·Jevgenia Zilberman-RudenkoOwen J T McCarty
May 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mareike DöhrmannKerstin Jurk
May 23, 2018·Cardiovascular Engineering and Technology·Jevgenia Zilberman-RudenkoMartin A Schreiber
Nov 16, 2018·Nature Reviews. Cardiology·Paola E J van der Meijden, Johan W M Heemskerk
May 21, 2019·Cellular and Molecular Bioengineering·Jevgenia Zilberman-RudenkoOwen J T McCarty
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Jul 12, 2019·Research and Practice in Thrombosis and Haemostasis·Vikram RaghunathanJoseph J Shatzel
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Jevgenia Zilberman-RudenkoOwen J T McCarty
Dec 11, 2017·Thrombosis Research·Bassem M MohammedDavid Gailani

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