Protein C or Protein S deficiency associates with paradoxically impaired platelet-dependent thrombus and fibrin formation under flow.
anticoagulation
coagulation
fibrin
platelet
thrombin
thrombophilia
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
20
07
2021
revised:
05
01
2022
accepted:
07
01
2022
entrez:
14
3
2022
pubmed:
15
3
2022
medline:
15
3
2022
Statut:
epublish
Résumé
Low plasma levels of protein C or protein S are associated with venous thromboembolism rather than myocardial infarction. The high coagulant activity in patients with thrombophilia with a (familial) defect in protein C or S is explained by defective protein C activation, involving thrombomodulin and protein S. This causes increased plasmatic thrombin generation. Assess the role of platelets in the thrombus- and fibrin-forming potential in patients with familial protein C or protein S deficiency under high-shear flow conditions. Whole blood from 23 patients and 15 control subjects was perfused over six glycoprotein VI-dependent microspot surfaces. By real-time multicolor microscopic imaging, kinetics of platelet thrombus and fibrin formation were characterized in 49 parameters. Whole-blood flow perfusion over collagen, collagen-like peptide, and fibrin surfaces with low or high GPVI dependency indicated an unexpected impairment of platelet activation, thrombus phenotype, and fibrin formation but unchanged platelet adhesion, observed in patients with protein C deficiency and to a lesser extent protein S deficiency, when compared to controls. The defect extended from diminished phosphatidylserine exposure and thrombus contraction to delayed and suppressed fibrin formation. The mechanism was thrombomodulin independent, and may involve negative platelet priming by plasma components.
Sections du résumé
Background
UNASSIGNED
Low plasma levels of protein C or protein S are associated with venous thromboembolism rather than myocardial infarction. The high coagulant activity in patients with thrombophilia with a (familial) defect in protein C or S is explained by defective protein C activation, involving thrombomodulin and protein S. This causes increased plasmatic thrombin generation.
Objective
UNASSIGNED
Assess the role of platelets in the thrombus- and fibrin-forming potential in patients with familial protein C or protein S deficiency under high-shear flow conditions.
Patients/Methods
UNASSIGNED
Whole blood from 23 patients and 15 control subjects was perfused over six glycoprotein VI-dependent microspot surfaces. By real-time multicolor microscopic imaging, kinetics of platelet thrombus and fibrin formation were characterized in 49 parameters.
Results and Conclusion
UNASSIGNED
Whole-blood flow perfusion over collagen, collagen-like peptide, and fibrin surfaces with low or high GPVI dependency indicated an unexpected impairment of platelet activation, thrombus phenotype, and fibrin formation but unchanged platelet adhesion, observed in patients with protein C deficiency and to a lesser extent protein S deficiency, when compared to controls. The defect extended from diminished phosphatidylserine exposure and thrombus contraction to delayed and suppressed fibrin formation. The mechanism was thrombomodulin independent, and may involve negative platelet priming by plasma components.
Identifiants
pubmed: 35284776
doi: 10.1002/rth2.12678
pii: S2475-0379(22)01169-4
pmc: PMC8900581
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e12678Informations de copyright
© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
Références
Thromb Haemost. 2017 Jan 5;117(1):90-98
pubmed: 27761580
Thromb Haemost. 1999 Jul;82(1):80-7
pubmed: 10456458
Circulation. 2015 Oct 13;132(15):1414-24
pubmed: 26330411
J Immunol Methods. 2012 Oct 31;384(1-2):21-4
pubmed: 22750541
J Thromb Haemost. 2010 Mar;8(3):445-53
pubmed: 20002539
Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):e97-e111
pubmed: 33267658
Haematologica. 2015 Jun;100(6):748-56
pubmed: 25769543
Thromb Haemost. 2007 Sep;98(3):543-56
pubmed: 17849042
J Thromb Haemost. 2008 Jun;6(6):995-1002
pubmed: 18489431
Blood. 1984 Dec;64(6):1297-300
pubmed: 6238642
Sci Rep. 2020 Jul 17;10(1):11910
pubmed: 32680988
Blood. 1995 Nov 15;86(10):3815-22
pubmed: 7579349
Arterioscler Thromb Vasc Biol. 2016 Apr;36(4):692-9
pubmed: 26848157
Blood. 2020 May 28;135(22):1969-1982
pubmed: 32276277
Thromb Res. 2021 Jul;203:46-56
pubmed: 33934017
Blood Adv. 2020 Jul 14;4(13):2953-2961
pubmed: 32603422
Physiol Rev. 2013 Jan;93(1):327-58
pubmed: 23303912
PLoS One. 2015 Aug 07;10(8):e0133523
pubmed: 26252207
Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):742-8
pubmed: 8640401
Thromb Haemost. 2004 Feb;91(2):334-44
pubmed: 14961162
Arteriosclerosis. 1987 Sep-Oct;7(5):456-62
pubmed: 2960305
Nat Rev Cardiol. 2019 Mar;16(3):166-179
pubmed: 30429532
Biomicrofluidics. 2016 Dec 15;10(6):064118
pubmed: 28058084
J Am Heart Assoc. 2020 Dec;9(23):e018917
pubmed: 33222589
Blood. 2008 Jul 1;112(1):19-27
pubmed: 18574041
Thromb Res. 2014 May;133 Suppl 2:S139-48
pubmed: 24862135
Br J Haematol. 1996 Oct;95(1):179-83
pubmed: 8857957
Expert Rev Hematol. 2016 Dec;9(12):1139-1149
pubmed: 27797270
FEBS Lett. 2005 Jun 13;579(15):3310-6
pubmed: 15943976
Int J Mol Sci. 2019 Jun 07;20(11):
pubmed: 31181592
J Thromb Haemost. 2008 Dec;6(12):2132-42
pubmed: 18826391
J Thromb Haemost. 2009 Nov;7(11):1774-8
pubmed: 19691480
Front Cardiovasc Med. 2021 Jan 08;7:608391
pubmed: 33490118
Blood Adv. 2020 Nov 10;4(21):5442-5448
pubmed: 33156924
Thromb Haemost. 2017 Jul 26;117(8):1588-1600
pubmed: 28536721
Haematologica. 2019 Jun;104(6):1256-1267
pubmed: 30545925
Lancet. 1993 Jan 16;341(8838):134-8
pubmed: 8093743
Nat Commun. 2014 Jul 16;5:4257
pubmed: 25027852
Blood. 2010 Jun 17;115(24):5069-79
pubmed: 20351310