Dilute thrombin time versus activated partial thromboplastin time to monitor Argatroban in critically ill patients

ABSTRACT

Background: Argatroban is a direct thrombin inhibitor currently licenced in the UK and USA for treatment of Heparin Induced Thrombocytopenia (HIT) and has been utilised as an alternative anticoagulant for critically ill COVID-19 patients. UK and US guidelines recommend Argatroban monitoring via activated partial thromboplastin time (aPTT), in critically ill patients, recommending ratios of between 1.5-3 times patient's baseline, without exceeding 100 s. This guidance is based on spiked pooled platelet poor plasma with increasing concentrations of Argatroban. Aim(s) * Does the aPTT demonstrate suitable linearity for Argatroban monitoring? * Are readily available alternatives more useful to indicate extent of Argatroban anticoagulation? Methods: From May to July 2021, 97 residual blood samples from 12 patients receiving Argatroban were processed for HemosIL APTT-SS, Thrombin time, Argatroban, and dilute thrombin time using ACL-TOP750 (Werfen, Bedford, USA). Performance was compared to commercial calibrators, across a therapeutic range from 0-2.08 mug/ml mimicking spiked plasma. Result(s) * No linearity was observed between Argatroban concentration and aPTT ratio (R2 value of 0.0778) in critically ill patient plasma compared to linearity for APTT ratios (R2 value of 0.9346) in commercial calibrators * Thrombin time produced good linearity with Argatroban (R2 value of 0.8473). Non-specific clot curve kinetic issues and exceeding acquisition times were noted. * Dilute thrombin time produced very good linearity with Argatroban (R2 value of 0.9443) Conclusion(s) In critically ill patients, aPTT ratio lacks a demonstrable linear response, unlike spiked and commercial plasmas. Non linearity is most likely due to other effects on the aPTT than Argatroban alone. 10.3% of patients exceeded an Argatroban concentration of 2.08 mug/ml with an aPTT ratio within guideline quoted ranges. Thrombin time and dTT demonstrated linearity. However, the thrombin time had non-specific clot curve kinetic abnormalities and some results exceeded acquisition time. No issues were seen with dilute thrombin time.