title: Locally applied recombinant plasmin results in effective thrombolysis in a porcine model of arteriovenous graft thrombosis.
abstract: OBJECTIVE
  Arteriovenous (AV) graft thrombosis is a frequent complication in patients undergoing hemodialysis. Thrombolytic therapy with tissue plasminogen activator (TPA) is hampered by the risk of bleeding complications. Locally delivered plasmin may have similar thrombolytic efficacy with a superior safety profile, so herein it was compared with TPA in a porcine model of AV graft thrombosis.
  
  
  METHODS
  AV grafts were created bilaterally between the carotid artery and jugular vein. Graft thrombosis was induced by clamping the grafts for 1 hour. On day 3, one graft was treated with a 2-mL local recombinant plasmin injection (10 mg; n = 10) with the contralateral graft being infused with TPA (10 mg, n = 8) or saline solution (n = 2). Thrombolytic efficacy was assessed by weighing the residual clot and released clot fragments.
  
  
  RESULTS
  After saline solution injection, the mean residual clot weight in the graft was 618 mg. Local administration of TPA showed the least residual clot in the graft (69 mg +/- 26), with large clot particles reaching the venous outflow (241 mg +/- 23). Plasmin treatment significantly reduced the released clot mass versus TPA (52 mg +/- 23; P < .05), whereas residual clot weight was greater compared with TPA treatment (140 mg +/- 22; P < .05). Overall thrombolytic activity of plasmin (ie, residual clot plus released clot) was significantly better than that of TPA (193 mg +/- 25 vs 310 mg +/- 35; P < .05).
  
  
  CONCLUSIONS
  The thrombolytic efficacy of recombinant plasmin was shown to be superior to that of TPA in this study.
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. i.hoefer@umcutrecht.nl
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Levi
authors.forename: Jim A
authors.initials: JA
authors.lastname: Reekers
authors.forename: Hence J M
authors.initials: HJ
authors.lastname: Verhagen
authors.forename: Joost C
authors.initials: JC
authors.lastname: Meijers
authors.forename: John E
authors.initials: JE
authors.lastname: Humphries
authors.forename: Joris I
authors.initials: JI
authors.lastname: Rotmans
mesh_terms: D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000008:administration & dosage / Q000235:genetics; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage; D013552:Swine; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D005341:Fibrinolysin