title: Safety of plasmin in the setting of concomitant aspirin and heparin administration in an animal model of bleeding.
abstract: Plasmin is a direct thrombolytic which has been shown to have a strikingly favorable benefit to risk profile in comparison with plasminogen activators, notably tissue plasminogen activator (t-PA). As heparin is known to increase the risk of hemorrhage when co-administered with a plasminogen activator, we asked whether adjunct antithrombotic agents such as aspirin and heparin would affect the safety of plasmin. Three groups of rabbits were administered plasmin at a dose (4 mg kg-1) designed to induce significant decreases in antiplasmin, fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline values, but not cause prolongation of the ear puncture bleeding time. In a blinded and randomized trial, the results show that an intravenous aspirin bolus plus heparin administered as a bolus followed by a maintenance continuous infusion did not significantly prolong the bleeding time during plasmin infusion. These data indicate that in the rabbit, concomitant use of aspirin plus heparin does not affect the safety of a therapeutic dose of plasmin.
authors.affiliation: Vascular Medicine Program, Los Angeles Orthopedic Hospital, and David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90007, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sadeghi
authors.forename: V J
authors.initials: VJ
authors.lastname: Marder
authors.forename: D
authors.initials: D
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Humphries
authors.forename: G A
authors.initials: GA
authors.lastname: Baumbach
authors.forename: G
authors.initials: G
authors.lastname: Jesmok
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001760:Bleeding Time; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005341:Fibrinolysin / Q000008:administration & dosage / Q000009:adverse effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects; D023421:Models, Animal; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000009:adverse effects
chemical_list: D005343:Fibrinolytic Agents; D006493:Heparin; D005341:Fibrinolysin; D001241:Aspirin