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

被引：29

作者：

Brouns, Sanne L. N. ^{[1
,2
]}

van Geffen, Johanna P. ^{[1
,2
]}

Campello, Elena ^{[3
]}

Swieringa, Frauke ^{[1
,2
,4
]}

Spiezia, Luca ^{[3
]}

van Oerle, Rene ^{[1
,2
]}

Provenzale, Isabella ^{[1
,2
]}

Verdoold, Remco ^{[1
,2
]}

Farndale, Richard W. ^{[5
]}

Clemetson, Kenneth J. ^{[6
]}

Spronk, Henri M. H. ^{[1
,2
]}

van der Meijden, Paola E. J. ^{[1
,2
]}

Cavill, Rachel ^{[7
]}

Kuijpers, Marijke J. E. ^{[1
,2
]}

Castoldi, Elisabetta ^{[1
,2
]}

Simioni, Paolo ^{[3
]}

Heemskerk, Johan W. M. ^{[1
,2
]}

机构：

[1] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Dept Biochem, POB 616, NL-6200 MD Maastricht, Netherlands

[2] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Dept Internal Med, POB 616, NL-6200 MD Maastricht, Netherlands

[3] Univ Padua, Med Sch, Dept Med, Padua, Italy

[4] Leibniz Inst Analyt Sci, Dept Prot Dynam, ISAS, Dortmund, Germany

[5] Univ Cambridge, Dept Biochem, Cambridge, England

[6] Univ Bern, Dept Haematol, Inselspital, Bern, Switzerland

[7] Maastricht Univ, Dept Data Sci & Knowledge Engn, Maastricht, Netherlands

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

PROTEIN-C; BLOOD-COAGULATION; GENERATION; RESISTANCE; FIBRIN; COLLAGEN; PLASMA; CONCENTRATE; HEMOSTASIS; ACTIVATION;

D O I：

10.1038/s41598-020-68438-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, this integrative phenotyping approach of platelet-fibrin thrombus formation has revealed interaction mechanisms of platelet-primed key haemostatic pathways with alterations in patients with (anti)coagulation defects. It can help as an important functional add-on whole-blood phenotyping.

引用

页数：15

共 45 条

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