Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 07 2020
17 07 2020
Historique:
received:
09
03
2020
accepted:
17
06
2020
entrez:
19
7
2020
pubmed:
19
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32680988
doi: 10.1038/s41598-020-68438-9
pii: 10.1038/s41598-020-68438-9
pmc: PMC7368055
doi:
Substances chimiques
Anticoagulants
0
Protein C
0
Thrombomodulin
0
Fibrin
9001-31-4
Thromboplastin
9035-58-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11910Subventions
Organisme : British Heart Foundation
ID : RG/15/4/31268
Pays : United Kingdom
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