Recombinant plasminogen activator inhibitor-1 reverses the bleeding tendency associated with the combined administration of tissue-type plasminogen activator and aspirin in rabbits

The Journal of Clinical Investigation
D E VaughanD Collen

Abstract

The major side effect of thrombolytic therapy is bleeding; however, the pathogenesis of this potential complication is not well understood. Accordingly, we examined the effects of aspirin and recombinant human tissue-type plasminogen activator (rt-PA) on serial template bleeding times and on hemostasis parameters in rabbits. The administration of intravenous aspirin (15 mg/kg) produced a slight prolongation in bleeding times, from 2.1 +/- 0.5 to 2.6 +/- 0.5 min (mean +/- SD, n = 26, P less than 0.01), whereas rt-PA (1 mg/kg per h for 2 h) lengthened the bleeding time from 2.4 +/- 0.3 to 3.2 +/- 0.6 min (n = 5, P = NS). Combination of aspirin with 0.5 mg/kg per h of rt-PA for 2 h prolonged the bleeding time from 2.5 +/- 0.4 to 6.2 +/- 0.9 min (n = 10, P less than 0.01), with an associated fibrinogen decrease of approximately 15%. The combination of aspirin with 1 mg/kg per h of rt-PA for 2 h prolonged the bleeding time from 3.0 +/- 0.3 to 8.3 +/- 1.4 min (n = 8, P less than 0.01) and simultaneously induced a decrease of plasma fibrinogen by approximately 40%. Virtually all animals treated with rt-PA and aspirin manifested a bleeding tendency, as evidenced by spontaneous rebleeding at sites of previously performed template bleedi...Continue Reading

References

Jun 1, 1987·The Journal of Clinical Investigation·J Loscalzo, D E Vaughan
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·T NyD J Loskutoff
Dec 1, 1986·The Journal of Clinical Investigation·D GinsburgT D Gelehrter
Oct 21, 1986·Biochemistry·D A Lawrence, D J Loskutoff
Dec 1, 1987·The Journal of Clinical Investigation·K A HajjarR L Nachman
Oct 6, 1988·The New England Journal of Medicine·J Loscalzo, E Braunwald
Feb 1, 1985·The Journal of Clinical Investigation·A I Schafer, B Adelman
Jul 1, 1973·The Journal of Clinical Investigation·S NiewiarowskiP Gillies

❮ Previous
Next ❯

Citations

Aug 1, 1990·Journal of the American College of Cardiology·J P ClozelS Roux
Jan 1, 1992·Progress in Cardiovascular Diseases·S R Levine, T G Brott
Jan 1, 1993·International Journal of Cardiology·D P de Bono, R S More
Jul 1, 1991·Stroke; a Journal of Cerebral Circulation·W M ClarkJ A Zivin
Dec 4, 1992·Annals of the New York Academy of Sciences·D Collen, H R Lijnen
Jan 4, 1990·The New England Journal of Medicine·B S Coller
Jan 1, 1992·Circulation·V J Marder
Aug 24, 2020·Biologicals : Journal of the International Association of Biological Standardization·Risa KashiwagiHirotsugu Tanaka
Sep 1, 1991·Progress in Cardiovascular Diseases·D CollenH K Gold

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.