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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Levy, JH; Despotis, GJ; Szlam, F; Olson, P; Meeker, D; Weisinger, A

Published Date

  • May 2002

Published In

Volume / Issue

  • 96 / 5

Start / End Page

  • 1095 - 1102

PubMed ID

  • 11981148

Pubmed Central ID

  • 11981148

International Standard Serial Number (ISSN)

  • 0003-3022

Digital Object Identifier (DOI)

  • 10.1097/00000542-200205000-00011


  • eng

Conference Location

  • United States