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Recombinant human transgenic antithrombin in cardiac surgery: a dose-finding study
Jerrold H Levy1, George J Despotis, Fania Szlam
1Department of Anesthesiology, Emory University School of Medicine and Division of Cardiothoracic Anesthesiology and Critical Care, Emory Healthcare, Atlanta, Georgia 30322, USA. jerrold_levy@emoryhealthcare.org
Anesthesiology
|May 1, 2002
Summary
Recombinant human antithrombin (rh-AT) effectively normalized antithrombin activity during cardiac surgery. This rh-AT supplementation improved heparin
Area of Science:
- Cardiology
- Hematology
- Pharmacology
Background:
- Acquired antithrombin III (AT) deficiency can reduce heparin efficacy in cardiac surgery with cardiopulmonary bypass (CPB).
- Investigating recombinant human AT (rh-AT) to address this deficiency is crucial for patient safety.
Purpose of the Study:
- To determine the pharmacodynamics and optimal dosage of rh-AT.
- To maintain normal AT activity during CPB.
- To optimize heparin anticoagulation and reduce hemostatic system activation in coronary artery bypass grafting (CABG) patients.
Main Methods:
- Thirty-six patients undergoing elective primary CABG were enrolled.
- Ten cohorts received varying doses of rh-AT (10-200 U/kg), with one cohort receiving 150 U/kg.
- A control group received a placebo.
Main Results:
- rh-AT doses of 75 U/kg normalized AT activity to 100 U/dl during CPB.
- rh-AT administration significantly increased activated clotting times (ACT) during CPB compared to placebo (844 ± 191 s vs. 531 ± 180 s).
- Increased rh-AT dosage showed an inverse relationship with fibrin monomer and D-dimer levels, indicating reduced coagulation activation.
Conclusions:
- rh-AT supplementation was well-tolerated in cardiac surgical patients.
- rh-AT increased ACT during CPB and decreased markers of coagulation activation (fibrin monomer, D-dimer).
- Transgenically produced rh-AT is a viable option for managing AT deficiency during cardiac surgery.