Does Antithrombotic Therapy Influence Residual Thrombus after Thrombolysis of Platelet-Rich Thrombus? Effects of Recombinant Hirudin, Heparin, or Aspirin

Jozef S. Mruk, Pierre Zoldhelyi, Mark W.I. Webster, Magda Heras, Diane E. Grill, David Holmes, Valentin Fuster, James H. Chesebro

Research output: Contribution to journalArticle

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Abstract

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 ×106 molecules/cm2 [P=.02]; 111In-platelets, 47±15 versus 13±2 ×106/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.

Original languageEnglish (US)
Pages (from-to)792-799
Number of pages8
JournalCirculation
Volume93
Issue number4
DOIs
StatePublished - Feb 15 1996

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Hirudins
Tissue Plasminogen Activator
Aspirin
Heparin
Thrombosis
Blood Platelets
Swine
Therapeutics
Reperfusion
Fibrin
Hirudin Therapy
Placebos
Endarterectomy
Partial Thromboplastin Time
Platelet Activation
Left Ventricular Function
Carotid Arteries
Thrombin
Dilatation
Angiography

Keywords

  • Fibrin
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Does Antithrombotic Therapy Influence Residual Thrombus after Thrombolysis of Platelet-Rich Thrombus? Effects of Recombinant Hirudin, Heparin, or Aspirin. / Mruk, Jozef S.; Zoldhelyi, Pierre; Webster, Mark W.I.; Heras, Magda; Grill, Diane E.; Holmes, David; Fuster, Valentin; Chesebro, James H.

In: Circulation, Vol. 93, No. 4, 15.02.1996, p. 792-799.

Research output: Contribution to journalArticle

Mruk, Jozef S. ; Zoldhelyi, Pierre ; Webster, Mark W.I. ; Heras, Magda ; Grill, Diane E. ; Holmes, David ; Fuster, Valentin ; Chesebro, James H. / Does Antithrombotic Therapy Influence Residual Thrombus after Thrombolysis of Platelet-Rich Thrombus? Effects of Recombinant Hirudin, Heparin, or Aspirin. In: Circulation. 1996 ; Vol. 93, No. 4. pp. 792-799.
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abstract = "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 ×106 molecules/cm2 [P=.02]; 111In-platelets, 47±15 versus 13±2 ×106/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.",
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T1 - Does Antithrombotic Therapy Influence Residual Thrombus after Thrombolysis of Platelet-Rich Thrombus?

T2 - Effects of Recombinant Hirudin, Heparin, or Aspirin

AU - Mruk, Jozef S.

AU - Zoldhelyi, Pierre

AU - Webster, Mark W.I.

AU - Heras, Magda

AU - Grill, Diane E.

AU - Holmes, David

AU - Fuster, Valentin

AU - Chesebro, James H.

PY - 1996/2/15

Y1 - 1996/2/15

N2 - 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 ×106 molecules/cm2 [P=.02]; 111In-platelets, 47±15 versus 13±2 ×106/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.

AB - 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 ×106 molecules/cm2 [P=.02]; 111In-platelets, 47±15 versus 13±2 ×106/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.

KW - Fibrin

KW - Platelets

KW - Thrombosis

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