Ecarin time superior to aptt in monitoring peghirudin effects

PEG-Hirudin is a long half-life polyethylene glycol derivative of rm-Hirudin. We investigated its antithrombotic effects and an optimal method for monitoring. In an open label Phase II study in 25 patients with chronic coronary or peripheral artery disease, nine patients received a sequential escalating dosing scheme (boluses, 0.03, 0.025, 0.25 mg/kg followed by corresponding infusions, 0.008, 0.015, 0.025 mg/kg/hr for 2 hr) and 16 patients received a higher dosing scheme (boluses, 0.10, 0.015, 0.015 mg/kg followed by corresponding infusions, 0.025, 0.03, 0.035 mg/kg/hr for 2 hr). Plasma Antithrombin Ha (Anti-Da), Fibrinopeptide A (fpA), Prothrombin Fragment 1.2 (pf 1.2), aPTT, Ecarin Times (ECT) were measured serially. Thrombus formation was measured using blood directly from patients with the ex-vivo chamber of Badimon. Mean plasma Anti-IIa, ECT and aPTT at the end of each dose infusion, increased linearly with dose. The area under the mean effect-time curves (baseline corrected) also increased proportionally with total dose for each dosing schedule except for aPTT which exhibited a less than proportional increase. A dose-dependent reduction with time was seen in plasma fpA levels but not in the pf1.2. Each dose significantly decreased thrombus size by about 40% (at moderate shear, 1620 sec^-1) compared to baseline. Linear regression analyses of all individual data indicated that plasma Anti-IIa levels are better correlated with ECT (r²=0.62) than with aPTT (r²=0.34) using results from a hospital laboratory. In summary, PEG-hirudin exhibited marked antithrombotic effects and its activity was better predicted using ECT than aPTT.