title: Does antithrombotic therapy influence residual thrombus after thrombolysis of platelet-rich thrombus? Effects of recombinant hirudin, heparin, or aspirin.
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.
  
  
  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 x 10(6) molecules/cm2 [P = .02]; 111In-platelets, 47 +/- 15 versus 13 +/- 2 x 10(6)/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.
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Mruk
authors.forename: P
authors.initials: P
authors.lastname: Zoldhelyi
authors.forename: M W
authors.initials: MW
authors.lastname: Webster
authors.forename: M
authors.initials: M
authors.lastname: Heras
authors.forename: D E
authors.initials: DE
authors.lastname: Grill
authors.forename: D R
authors.initials: DR
authors.lastname: Holmes
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: J H
authors.initials: JH
authors.lastname: Chesebro
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006487:Hemostasis; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; D005337:Fibrin; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin