Streptokinase inhibits acute platelet thrombus formation in stenosed dog coronary arteries.
Previous evidence has suggested that plasmin, in addition to its proteolytic action on fibrin, may affect platelet function. To test the effects of plasmin generated in vivo by the thrombolytic agent streptokinase (SK) on platelet-dependent vascular occlusion, we have used a well-established canine model of experimental coronary artery stenosis which produces platelet aggregate-dependent cyclical variations in coronary blood flow. Infusion of SK into 22 dogs at doses sufficient to cause a systemic lytic state led to complete abolition of cyclical blood flow reductions (CFR's) at sites of coronary artery injury. Inhibition of coronary platelet occlusion was associated with marked prolongations of the bleeding time (from 3.2 ± 0.6 min before to 14 ± 5 min after SK infusion, mean ± SD, n = 22). Despite the striking effects of SK on in vivo platelet-vessel wall interactions, only platelet aggregation in response to collagen was diminished among the ex vivo parameters of platelet function that were studied simultaneously. Platelet aggregation in response to other agonists, thromboxane A2 production, monoclonal antibody binding to platelet membrane glycoprotein (Gp) IIb-IIIa, Gp Ib-dependent botrocetin-induced platelet aggregation and platelet levels of cyclic AMP were not significantly altered. Therefore the thrombolytic agent streptokinase appears to cause important inhibitory effects on in vivo platelet reactivity with injured vascular intimal surfaces, possibly due to localised changes in platelet aggregate formation in the microenvironment of exposed collagen. These findings suggest that plasmin generated by thrombolytic agents may exhibit platelet inhibitory activity, and that this effect may be important in reestablishing blood flow in certain forms of platelet-mediated arterial thromboses.
Section of Hematology, Department of Medicine, University of Wisconsin Medical School, Madison, WI, 53792.
J D
JD
Folts
B S
BS
Schwartz
M H
MH
Kroll
A I
AI
Schafer