title: The dependence of activation of platelets by a plasminogen activator on the evolution of thrombin activity.
abstract: Both augmentation of thrombin activity and activation of platelets have been reported to accompany administration of plasminogen activators in vivo. To determine whether the platelet activation is a consequence or a cause of the procoagulant effects, we assessed the effects of t-PA on spontaneous activation and aggregation of platelets and on clotting in recalcified human whole blood. Spontaneous activation of platelets occurred in the stirred samples 8.9 +/- 2 minutes (n = 5) after recalcification. Aggregation and clotting followed immediately afterward. Activation, aggregation and clotting were accelerated in a dose-dependent manner by 3 minutes of preincubation with t-PA (2-30 micrograms/ml) before recalcification. The procoagulant effect of t-PA (5 micrograms/ml) was abolished by concomitant incubation with hirudin (0.5 nM) or aprotinin (200 KIU/ml) consistent with the hypothesis of plasmin-mediated evolution of thrombin being responsible for the procoagulant effect. However, platelets could be activated independently by other agonists (collagen, 3 micrograms/ml; and ADP, 25 microM) in the presence of hirudin. Despite the procoagulant effect of t-PA, aggregation to collagen (2-5 micrograms/ml) and PAF (0.9 microM) was diminished in samples incubated with t-PA for 30 minutes (37 degrees C). Fibrinogen degradation products elaborated during this interval (25.6 micrograms/ml; n = 3) were responsible for this anti-aggregatory effect. The results indicate that platelet activation in recalcified whole blood depends on procoagulant effects of t-PA.
authors.affiliation: Cardiovascular Division, Washington University, St. Louis, Missouri.
authors.forename: S R
authors.initials: SR
authors.lastname: Torr
authors.forename: P R
authors.initials: PR
authors.lastname: Eisenberg
authors.forename: B E
authors.initials: BE
authors.lastname: Sobel
mesh_terms: D007611:Aprotinin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D005341:Fibrinolysin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D006629:Hirudins; D007611:Aprotinin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D002122:Calcium Chloride