Recombinant human transgenic antithrombin in cardiac surgery: A dose-finding study

Jerrold H. Levy, George J. Despotis, Fania Szlam, Peter Olson, David Meeker, Andrew Weisinger

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background: Acquired antithrombin III (AT) deficiency may render heparin less effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT) needed to maintain normal AT activity during CPB, optimize the anticoagulant response to heparin, and attenuate excessive activation of the hemostatic system in patients undergoing coronary artery bypass grafting. Methods: Thirty-six patients scheduled to undergo elective primary coronary artery bypass grafting and who had received heparin for 12 h or more before surgery were enrolled in the study. Ten cohorts of three patients each received rh-AT in doses of 10, 25, 50, 75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg of rh-AT, and a control group of six patients received placebo. Results: Antithrombin III activity exceeded 600 U/dl before CPB at the highest dose (200 U/kg). Doses of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB. Activated clotting times during CPB were significantly (P < 0.0001) greater in patients who received rh-AT (844 ± 191 s) compared with placebo patients (531 ± 180 s). Significant (P = 0.001) inverse relations were observed between rh-AT dose and both fibrin monomer (r = - 0.51) and D-dimer (r = - 0.51) concentrations. No appreciable adverse events were observed with any rh-AT doses used in the study. Conclusions: Supplementation of native AT with transgenically produced protein (rh-AT) in cardiac surgical patients was well tolerated and resulted in higher activated clotting times during CPB and decreased levels of fibrin monomer and D-dimer.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalAnesthesiology
Volume96
Issue number5
DOIs
StatePublished - May 13 2002

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