Ecarin-based coagulation monitoring of argatroban in patients with heparin-induced thrombocytopenia: a prospective observational study.

Abstract

The anticoagulant argatroban, a direct thrombin inhibitor, serves as an alternative to heparin in patients with heparin-induced thrombocytopenia (HIT). However, its dose titration using activated partial thromboplastin time (aPTT) has limitations. We aimed to investigate whether ecarin clotting time (ECA-CT) correlates better with plasma argatroban concentrations than aPTT. In this single-centre, observational study, 22 patients with HIT undergoing cardiac surgery and receiving argatroban anticoagulation were monitored over 5 days. The outcomes assessed were aPTT and ecarin clotting time (ECA-CT ClotPro®) values, plasma argatroban concentrations measured by a functional assay, and their correlations with each other. Ecarin clotting time demonstrated a strong correlation with plasma argatroban concentrations (r=0.881, 95% confidence interval [CI] 0.790-0.934, P<0.0001), but aPTT was not correlated (r=0.12, 95% CI -0.182 to 0.412, P=0.843). The association between plasma argatroban concentration and aPTT was near-random above aPTT values >55 s, and was best described by a nonlinear approximation. Factor XII was the main independent driver of aPTT variability apart from argatroban concentration. Conversely, ecarin clotting time was independently affected by Factor II, X, and XI apart from argatroban. This study presents ECA-CT as a reliable point-of-care test for monitoring argatroban concentration in patients with HIT. aPTT demonstrated a pronounced inability to track argatroban concentrations, especially when aPTT was >55 s. These findings highlight the need to reconsider optimal anticoagulation targets when using argatroban.