Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation.

Scientific Reports
Sanne L N BrounsJohan W M Heemskerk

Abstract

In haemostasis and thrombosis, platelet, coagulation and anticoagulation pathways act together to produce fibrin-containing thrombi. We developed a microspot-based technique, in which we assessed platelet adhesion, platelet activation, thrombus structure and fibrin clot formation in real time using flowing whole blood. Microspots were made from distinct platelet-adhesive surfaces in the absence or presence of tissue factor, thrombomodulin or activated protein C. Kinetics of platelet activation, thrombus structure and fibrin formation were assessed by fluorescence microscopy. This work revealed: (1) a priming role of platelet adhesion in thrombus contraction and subsequent fibrin formation; (2) a surface-independent role of tissue factor, independent of the shear rate; (3) a mechanism of tissue factor-enhanced activation of the intrinsic coagulation pathway; (4) a local, suppressive role of the anticoagulant thrombomodulin/protein C pathway under flow. Multiparameter analysis using blood samples from patients with (anti)coagulation disorders indicated characteristic defects in thrombus formation, in cases of factor V, XI or XII deficiency; and in contrast, thrombogenic effects in patients with factor V-Leiden. Taken together, th...Continue Reading

References

Feb 1, 1972·British Journal of Haematology·P N Walsh
Oct 1, 1996·British Journal of Haematology·M LozanoA Ordinas
May 2, 1997·The Journal of Biological Chemistry·B B SorensenL V Rao
Jun 10, 2005·FEBS Letters·Björn Dahlbäck, Bruno O Villoutreix
Oct 29, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Dougald M Monroe, Maureane Hoffman
Jun 9, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel MackmanNigel S Key
Apr 18, 2009·Blood·Paola E J van der MeijdenJohan W M Heemskerk
Dec 17, 2009·Journal of Thrombosis and Haemostasis : JTH·E Castoldi, J Rosing
Aug 2, 2011·Seminars in Thrombosis and Hemostasis·Björn Dahlbäck
Nov 9, 2011·Nature Medicine·Shaun P Jackson
Apr 21, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas V ColaceScott L Diamond
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jul 4, 2012·Journal of Immunological Methods·Ronald CarnemollaVladimir R Muzykantov
Oct 2, 2012·Journal of Thrombosis and Haemostasis : JTH·R LoeffenH M H Spronk
Oct 31, 2012·Journal of Thrombosis and Haemostasis : JTH·J W M HeemskerkJ M E M Cosemans
Jan 11, 2013·Physiological Reviews·Henri H VersteegPieter H Reitsma
May 24, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Marijke J E KuijpersJudith M E M Cosemans
Jul 17, 2014·Nature Communications·Susanne M de WittJudith M E M Cosemans
May 16, 2015·Blood·Elmina Mammadova-BachMartine Jandrot-Perrus
Aug 19, 2015·Blood·Osama M AlshehriSteve P Watson
Jan 16, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Jevgenia Zilberman-RudenkoOwen J T McCarty
Feb 6, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Frauke SwieringaPaola E J van der Meijden
Feb 2, 2018·Annals of Hematology·Luca SpieziaPaolo Simioni
Dec 14, 2018·Haematologica·Johanna P van GeffenJohan W M Heemskerk

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Citations

Dec 4, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Gina PerrellaJohan W M Heemskerk
Jan 26, 2021·Frontiers in Cardiovascular Medicine·Jiayu WuConstance C F M J Baaten
Feb 5, 2021·Research and Practice in Thrombosis and Haemostasis·Danique L van den KerkhofIngrid Dijkgraaf
Feb 25, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Marta BrambillaMarina Camera
Jul 3, 2021·International Journal of Molecular Sciences·Elena RezusCiprian Rezus
Sep 10, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Gina PerrellaJohan W M Heemskerk

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Methods Mentioned

BETA
blood drawing

Software Mentioned

Matlab
BFTree
SMO
RBFNetwork
REPTree
Thrombinoscope
R
FT
Fiji
PART

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