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(Circulation. 1995;93:792-799.)
© 1995 American Heart Association, Inc.

Articles

Does Antithrombotic Therapy Influence Residual Thrombus After Thrombolysis of Platelet-Rich Thrombus?

Effects of Recombinant Hirudin, Heparin, or Aspirin

Presented in part at the 63rd Scientific Sessions of the American Heart Association, Dallas, Tex, November 12-15, 1990; 40th Annual Scientific Session, American College of Cardiology, Atlanta, Ga, March 3-7, 1991; and 41st Annual Scientific Session, American College of Cardiology, Dallas, Tex, April 12-16, 1992.

Jozef S. Mruk, MD, PhD; Pierre Zoldhelyi, MD; Mark W.I. Webster, MB, CHB; Magda Heras, MD; Diane E. Grill, MS; David R. Holmes, Jr, MD; Valentin Fuster, MD; James H. Chesebro, MD

From the Division of Cardiovascular Diseases and Internal Medicine (J.S.M., P.Z., M.W.I.W., M.H., D.E.G., D.R.H. Jr., J.H.C.), Mayo Clinic and Mayo Foundation, Rochester, Minn; and Mount Sinai Medical Center and School of Medicine (V.F.), New York, NY.

Correspondence to James H. Chesebro, MD, Cardiovascular Institute, Box 1030, Mount Sinai Medical Center, One Gustave L. Levy Pl, New York, NY 10029-6574.

Background Thrombolysis to normal flow in patients with acute myocardial infarction preserves left ventricular function and decreases mortality. Failure of early reperfusion, reocclusion, or residual thrombus may be due to concurrent activation of the platelet-coagulation system. Thus, we hypothesized that the best concomitant antithrombotic therapy (recombinant [r]-hirudin, heparin, or aspirin) will maximally accelerate thrombolysis by r–tissue-type plasminogen activator (rTPA) and reduce residual thrombus.

Methods and Results Occlusive thrombi were formed in the carotid arteries of 29 pigs (by balloon dilatation followed by endarterectomy at the site of injury-induced vasospasm) and matured for 30 minutes before rTPA was started, with or without antithrombotic therapy. Thrombolysis was assessed with the use of angiography and measurement of residual thrombus. Pigs were allocated to one of five treatments: placebo, rTPA, rTPA plus r-hirudin, rTPA plus heparin, or rTPA plus intravenous aspirin. No placebo-treated pig reperfused. Two of six animals treated with rTPA alone reperfused compared with seven of seven animals treated with rTPA plus r-hirudin (reperfusion time, 33±10 minutes), six of seven animals treated with rTPA plus heparin (reperfusion time, 110±31 minutes), and two of six animals with rTPA plus aspirin. The activated partial thromboplastin time was prolonged in only the rTPA plus r-hirudin group (25±0.1 times baseline) and the rTPA plus heparin group (5.3±0.2 times baseline). Residual ¹¹¹In-platelet and ¹²⁵I-fibrin(ogen) depositions were lower in the heparin-treated group and lowest in the r-hirudin–treated group (heparin versus hirudin, respectively; incidence of residual macroscopic thrombus was six of six animals versus two of seven [P=.01]; ¹²⁵I-fibrin(ogen), 170±76 versus 48±6 x10⁶ molecules/cm² [P=.02]; ¹¹¹In-platelets, 47±15 versus 13±2 x10⁶/cm², P=.10). No pigs developed spontaneous bleeding.

Conclusions Thrombin inhibition with heparin or r-hirudin significantly accelerated thrombolysis of occlusive platelet-rich thrombosis, but only the best antithrombotic therapy (r-hirudin) eliminated or nearly eliminated residual thrombus.

Key Words: thrombosis • platelets • fibrin

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