Protein C or Protein S deficiency associates with paradoxically impaired platelet‐dependent thrombus and fibrin formation under flow

Research and Practice in Thrombosis and Haemostasis

Paolo Simioni¹  Cristiana Bulato¹  Luca Spiezia¹  Elena Campello¹  Johanna P. vanGeffen²  Bibian M. E. Tullemans²  Marijke J. E. Kuijpers²  Sanne L. N. Brouns²  Paola E. J. van derMeijden²  Gina Perrella²  Henri M. H. Spronk²  Johan W. M. Heemskerk²  René vanOerle² 

[1] Department of Medicine University of Padua Medical School Padova Italy;Departments of Biochemistry and Internal Medicine CARIM Maastricht University Medical Centre Maastricht The Netherlands;

关键词: anticoagulation;    coagulation;    fibrin;    platelet;    thrombin;    thrombophilia;   

DOI  :  10.1002/rth2.12678

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown