Safety of catheter-delivered plasmin in patients with acute lower extremity arterial or bypass graft occlusion: phase I results.
J Thromb Haemost
; 10(6): 985-91, 2012 Jun.
Article
de En
| MEDLINE
| ID: mdl-22487025
ABSTRACT
BACKGROUND:
Current treatment of acute peripheral artery or bypass graft occlusion utilizes catheter-directed thrombolysis of a plasminogen activator (PA). Plasmin is a direct-acting thrombolytic with a striking safety advantage over PA in preclinical models.OBJECTIVES:
To report the first use of purified plasmin for acute lower extremity arterial or bypass graft thrombosis in a phase I dose-escalation study of a catheter-delivered agent.METHODS:
Eighty-three patients with non-embolic occlusion of infrainguinal native arteries or bypass grafts were enrolled (safety population) into seven sequential dose cohorts to receive 25-175 mg of plasmin by intrathrombus infusion over 5 h. Arteriograms were performed at baseline, 2 h, and 5 h, and subjects were monitored for 30 days for clinical outcomes and laboratory parameters of systemic fibrinolysis.RESULTS:
Major bleeding occurred in four patients (4.8%), and minor bleeding alone in 13 (15.7%), with no trend towards more bleeding at higher dosages of plasmin. There was a trend towards lower plasma concentrations of fibrinogen, α(2) -antiplasmin and α(2) -macroglobulin with increasing doses of plasmin, but the nadir fibrinogen concentration was > 350 mg dL(-1) at the highest plasmin dose. Individual nadir values were above 200 mg dL(-1) in 82 of 83 subjects, and were not different in patients with or without bleeding. Thrombolysis (≥ 50%) occurred in 79% of subjects receiving 125-175 mg of plasmin, as compared with 50% who received 25-100 mg.CONCLUSIONS:
Catheter-delivered plasmin can be safely administered to patients with acute lower extremity arterial occlusion at dosages of 25-175 mg.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Artériopathies oblitérantes
/
Cathétérisme périphérique
/
Traitement thrombolytique
/
Fibrinolysine
/
Membre inférieur
/
Fibrinolytiques
/
Occlusion du greffon vasculaire
Type d'étude:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limites:
Aged80
Pays/Région comme sujet:
Africa
/
America do norte
/
America do sul
/
Brasil
/
Europa
Langue:
En
Journal:
J Thromb Haemost
Sujet du journal:
HEMATOLOGIA
Année:
2012
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique