Inhibition of tissue plasminogen activator activity by aspirin in vivo and
its relationship to levels of tissue plasminogen activator inhibitor
antigen, plasminogen activator and their complexes
RI Levin, PC Harpel, JG Harpel and PA Recht
Division of Cardiology, New York University School of Medicine, NY.
The observation that aspirin inhibits the increment in tissue plasminogen
activator (t-PA) activity induced by venous occlusion of the forearm became
controversial with the publication of several nonconfirmatory studies. The
current study was performed to confirm the original observation and
determine the mechanism by which aspirin suppresses the incremental t-PA
activity induced by venous occlusion. Aspirin (650 mg/d X 2) caused no
change in resting levels of t-PA antigen (t-PA:Ag) or activity, plasminogen
activator inhibitor 1 antigen (PAI-1:Ag), or activity or t-PA-PAI-1
complexes. In contrast, aspirin reduced the increments induced by venous
occlusion as follows: t-PA:Ag by 45% (P = .001); t-PA activity (euglobulin
lysis time, ELT) by 43% (P = .006); and t-PA activity (alpha 2-plasmin
inhibitor-plasmin complexes, PIPC) by 41% (P = .003). The inhibition of
incremental t-PA activity measured as ELT or PIPC was linearly correlated
with the inhibition of incremental t-PA:Ag (respectively, r = .75, P less
than .02; r = .67, P less than .05). Aspirin had no effect on the increment
in PAI-1:Ag induced by venous occlusion, but similar to the effect on t-
PA:Ag, aspirin induced a 51% inhibition of the increment in t-PA-PAI-1
complex formation. Aspirin did not alter the ability of alpha 2-plasmin
inhibitor to bind plasmin, nor the ability of plasma to support the
fibrin-catalyzed generation of plasmin by t-PA, nor the subsequent
formation of PIPC. Aspirin inhibits the t-PA activity induced by venous
occlusion primarily by inhibiting the release of t-PA antigen.
Volume 74,
Issue 5,
pp. 1635-1643,
10/01/1989
Copyright © 1989 by The American Society of Hematology
