Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation
| Autor: | Sanne L. N. Brouns, Elisabetta Castoldi, Isabella Provenzale, Remco Verdoold, Henri M. H. Spronk, Johan W. M. Heemskerk, Paolo Simioni, Rachel Cavill, Marijke J E Kuijpers, Luca Spiezia, Frauke Swieringa, Paola E. J. van der Meijden, Elena Campello, Rene van Oerle, Richard W. Farndale, Johanna P. van Geffen, Kenneth J. Clemetson |
|---|---|
| Přispěvatelé: | Apollo - University of Cambridge Repository, Biochemie, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, Promovendi CD, Interne Geneeskunde, RS: Carim - B04 Clinical thrombosis and Haemostasis, DKE Scientific staff, RS: FSE DACS, RS: FSE DACS Mathematics Centre Maastricht, MUMC+: HVC Pieken Trombose (9), RS: Carim - B01 Blood proteins & engineering, Farndale, Richard [0000-0001-6130-8808] |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Thrombomodulin lcsh:Medicine 030204 cardiovascular system & hematology 692/4019/592/1339 ACTIVATION 0302 clinical medicine Platelet lcsh:Science 610 Medicine & health BLOOD-COAGULATION Multidisciplinary biology PLASMA Chemistry article Middle Aged Phenotype Coagulation PROTEIN-C Female Platelets Adult Blood Platelets 631/250/2500 Fibrin Thromboplastin 03 medical and health sciences Tissue factor medicine Humans HEMOSTASIS Platelet activation Thrombus Blood Coagulation lcsh:R Anticoagulants Thrombosis medicine.disease Coagulation system COLLAGEN FIBRIN CONCENTRATE Kinetics 030104 developmental biology Case-Control Studies Hemostasis Hemorheology biology.protein Cancer research lcsh:Q RESISTANCE Protein C GENERATION |
| Zdroj: | Brouns, Sanne L N; van Geffen, Johanna P; Campello, Elena; Swieringa, Frauke; Spiezia, Luca; van Oerle, René; Provenzale, Isabella; Verdoold, Remco; Farndale, Richard W; Clemetson, Kenneth J.; Spronk, Henri M H; van der Meijden, Paola E J; Cavill, Rachel; Kuijpers, Marijke J E; Castoldi, Elisabetta; Simioni, Paolo; Heemskerk, Johan W M (2020). Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation. Scientific reports, 10(1), p. 11910. Springer Nature 10.1038/s41598-020-68438-9 Scientific Reports Scientific Reports, 10(1):11910. Nature Publishing Group Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68438-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|