title: Sensitivity of a modified ACT test to levels of bivalirudin used during cardiac surgery.
abstract: Assessment of anticoagulation status during cardiac surgery can be valuable for novel therapeutics, including direct thrombin inhibitors. The ecarin clotting time (ECT) has been reported to be sensitive for monitoring of bivalirudin in cardiac surgery but is not commercially available. The activated clotting time (ACT), commonly used for heparin monitoring, may display a lack of sensitivity to alternative anticoagulants when used in on-pump cardiac surgery. Both the ACT and ECT have been successfully used for monitoring bivalirudin anticoagulation in off-pump cardiac surgery. A new ACT, the ACTT, was developed to increase the linearity of the clotting time response to bivalirudin at higher concentrations. After Ethics Committee approval, a pilot study was performed to evaluate the feasibility of using bivalirudin for on-pump cardiac surgery and to evaluate dosing of bivalirudin in terms of the pharmacokinetic and safety profile in patients undergoing coronary artery bypass graft (CABG) surgery. Secondary objectives included an assessment of the anticoagulation profile and correlation of the response seen with various ACTs and the ECT with the plasma bivalirudin concentration in the patients' blood. After informed consent, 10 sequential patients presenting for elective cardiac surgery requiring cardiopulmonary bypass received bivalirudin anticoagulation in lieu of heparin. Dosing was fixed (1.0 mg/kg bolus followed by a 2.5 mg/kg/h infusion) and not titrated on the basis of coagulation test results. At baseline and 15-minute intervals, blood samples were collected for ACT (ACTT, Celite, kaolin, ACT+), ECT, and bivalirudin plasma level measurements. Over the range of bivalirudin plasma concentrations in this study, all clot-based systems examined were prolonged according to concentration and showed good correlation with bivalirudin plasma levels. The ACTT and the ECT showed greater sensitivity to bivalirudin (-28.5 sec/microg/ml bivalirudin) compared with the other ACTs evaluated (approximately 14 sec/microg/ml). This difference in sensitivity was also evident at low concentrations of bivalirudin (<10 microg/ ml), with the ECT and ACTT showing slopes near 40, and the ACT slopes varying from 18 to 27 sec/microg/ml. The ACTT assay is sensitive to levels of bivalirudin and may offer a simple method for monitoring bivalirudin during cardiac surgery.
authors.affiliation: Clinical Affairs, ITC, Edison, New Jersey 07039, USA. mlzucker@itcmed.com
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Zucker
authors.forename: Andreas
authors.initials: A
authors.lastname: Koster
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.forename: Frank M
authors.initials: FM
authors.lastname: Laduca
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D002315:Cardiopulmonary Bypass / Q000379:methods*; D001026:Coronary Artery Bypass; D005240:Feasibility Studies; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin