Open AccessProtein C or Protein S deficiency associates with paradoxically impaired platelet‐dependent thrombus and fibrin formation under flow
Author(s) -
Brouns Sanne L. N.,
Tullemans Bibian M. E.,
Bulato Cristiana,
Perrella Gina,
Campello Elena,
Spiezia Luca,
Geffen Johanna P.,
Kuijpers Marijke J. E.,
Oerle René,
Spronk Henri M. H.,
Meijden Paola E. J.,
Simioni Paolo,
Heemskerk Johan W. M.
Publication year - 2022
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12678
Subject(s) - fibrin , thrombus , platelet , chemistry , medicine , immunology
Background 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 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 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 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.