Ecarin clotting time but not aPTT correlates with PEG-Hirudin plasma activity

Background: Novel antithrombotic agents such as hirudin have shown promise in the therapy of acute coronary syndromes. PEG-hirudin (polyethyleneglycol conjugated hirudin) has been developed to provide a longer plasma half-lif e and more stable antithrombotic plasma levels. Privious trials indicated a narrow therapeutic window for hirudin and a number of aPTT (activated part ial thromboplastin time)-monitored trials investigating hirudin in acute co ronary syndromes had to be stopped because of intracranial bleeding complic ations. Objectives: The present study evaluates the ecarin clotting time (ECT), a p arameter based on the conversion of prothrombin by the snake venom enzyme e carin, for the monitoring of PEG-hirudin therapy. Methods: Plasma from either healthy volunteers (n=20) or from patients (n=1 0) suffering from unstable angina pectoris (UAP) was spiked with increasing PEG-hirudin concentrations. In a prospective randomized clinical trial pat ients with UAP were treated with intravenous PEG-hirudin or heparin over 72 hours. Patients were randomized to the following treatment groups: (1) hep arin control group, n=15; (2) PEG-hirudin low dose (0.1 mg/kg bolus, 0.01 m g/kg/h infusion), n=19; (3) intermediate dose (0.15 mg/kg and 0.015 mg/kg/h ), n=17; 4) high-dose (0.2 mg/kg and 0.02 mg/kg/h), n=16. Spiked plasma sam ples and plasma from UAP patients treated with i.v. PEG-hirudin were analyz ed for aPTT, ECT, and PEG-hirudin levels. Results: A linear correlation up to the highest therapeutic concentrations could be observed between PEG-hirudin plasma concentrations and the ECT. Th is was true for both plasma samples spiked with PEG-hirudin in vitro as wel l as for samples taken from patients treated with i.v. PEG-hirudin (correla tion coefficient 0.9, respect.) In contrast the aPTT did not show a reliabl e linear correlation to PEG-hirudin concentrations. Conclusion: Monitoring of PEG-hirudin therapy by ECT may help to avoid inad equate anticoagulation or overdosing. Thus, the safety and efficacy profile of PEG-hirudin therapy is likely to be enhanced by ECT monitoring.