title: Co-administration of aprotinin and epsilon-aminocaproic acid during cardiopulmonary bypass in a swine model.
abstract: Despite the beneficial effects of pharmacological interventions to prevent bleeding and to reduce the need for autogeneic blood, there are concerns that these agents induce a prothrombotic state. The purpose of this study was to examine the coagulation phenomena influenced by the coadministration of epsilon-aminocaproic acid (EACA) and aprotinin during cardiopulmonary bypass (CPB). A swine model of CPB was utilized in this study. During 120 min of CPB, treatment animals (N = 5) received 6 x 10(6) Kiu of aprotinin and 30 grams of EACA; whereas, control animals (N = 3) received an equal volume of 0.9% saline. Indices of thrombogenicity included hematological variables, gross pathology, and circuit examination for the presence of thrombus. The application of both antifibrinolytics resulted in an increase use of heparin. Total heparin requirements were significantly different between treatment group (58,800 +/- 3493 iu) versus control group (51,000 +/- 3464 iu). D-dimer concentration was also significantly higher in the control group (500-1000 ng mL-1) than in the treatment group (250-500 ng mL-1) at 5 and 30 min postprotamine. Other coagulation markers tested were not observed to be statistically significant between groups. Thromboelastographic (TEG) index decreased in the treatment group during the surgical procedure and bypass from 2.74 +/- 2.9 to -1.36 +/- 4.1 as compared to an increase from 2.62 +/- 2.9 to 4.05 +/- 0.4 in the control group. Pathologic analysis revealed occurrences of thrombus formation in small vessels in the lung and kidney glomeruli of treatment animals. The concurrent use of both aprotinin and EACA may induce a prothrombotic or coagulant state as determined by histological assessment.
authors.affiliation: Division of Clinical Perfusion Education, School of Allied Health Professions, University of Nebraska Medical Center, Omaha, Nebraska, USA. Vangs@trinity-health.org
authors.forename: S N
authors.initials: SN
authors.lastname: Vang
authors.forename: A H
authors.initials: AH
authors.lastname: Stammers
authors.forename: B L
authors.initials: BL
authors.lastname: Mejak
authors.forename: E D
authors.initials: ED
authors.lastname: Rauch
authors.forename: T W
authors.initials: TW
authors.lastname: Viessman
authors.forename: N L
authors.initials: NL
authors.lastname: Bruda
authors.forename: T
authors.initials: T
authors.lastname: Yang
mesh_terms: D015119:Aminocaproic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007611:Aprotinin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D006490:Hemostatics / Q000008:administration & dosage* / Q000494:pharmacology; D023421:Models, Animal; D013552:Swine; D014481:United States
chemical_list: D000933:Antifibrinolytic Agents; D006490:Hemostatics; D007611:Aprotinin; D015119:Aminocaproic Acid