Important Regulatory Role of Activated Platelet-Derived Procoagulant Activity in the Propagation of Thrombi Formed Under Arterial Blood Flow Conditions

摘要

Background: The functional links between the activation of platelets and the coagulation system have not beenclarified.Methods and Results: Immobilized collagen fibrils were perfused with human blood containing fluoresceinatedplatelets in the presence of various concentrations of thrombin inhibitor. Coagulant activity around platelet thrombiwas detected using a FITC-conjugated antibody against the fibrin monomer complex (F-405). Intra-cytosoliccalcium ion concentrations ([Ca~(2+)]i) in individual platelets and the volume of thrombi were detected with anultrafast confocal laser microscope equipped with a piezo-motor control unit. The volume of platelet thrombiformed after 8 min of blood perfusion in the presence of 10,25,50, and 100mumol/L argatroban was 7.69+-0.46mum~3,6.61+-1.96mum~3, 3.63+-1.54mum3, and 1.67+-0.75mum3, respectively. There was a positive correlation between thevolume of platelet thrombi and the amount of fibrin monomer complex produced around them. The [Ca~(2+)]i of theplatelets forming the thrombi oscillated between a minimum of 92.0+-57.4nmoI/L, 120.1+-68.1nmol/L, and amaximum of 217.6+-131.5nmol/L, 367.6+-189.1nmol/L, respectively, in the presence of 100 and 10mumol/Largatroban.Conclusions: The results suggest a crucial role of coagulant activity in both the generation of fibrin and thegrowth of platelet thrombi.