The dependence of activation of platelets by a plasminogen activator on the evolution of thrombin activity.
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.
Torr
S R
SR
Cardiovascular Division, Washington University, St. Louis, Missouri.
Eisenberg
P R
PR
Sobel
B E
BE
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*
D006629:Hirudins; D007611:Aprotinin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D002122:Calcium Chloride