PB1034 - Monitoring of argatroban in critical ill patients: a prospective study comparing aPTT, point-of-care viscoelastic testing with ecarin clotting time and dTT to LC/MS/MS

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Lars Heubner, MD

Anesthesiology Resident / post-doc Research Fellow
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Department of Anesthesiology and Intensive Care Medicine, Dresden, Saxony, Germany
Dresden, Sachsen, Germany

Co-Author(s)

RO

Reinhard Oertel

Laboratory head Clinical Pharmacology
Institute of Clinical Pharmacology, Faculty of Medicine „Carl Gustav Carus“, Technische Universität Dresden, Dresden, Germany
Dresden, Sachsen, Germany
AG

Andreas Güldner

Senior physician
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Department of Anesthesiology and Intensive Care Medicine, Dresden, Saxony, Germany
Dresden, Sachsen, Germany
OV

Oliver Vicent

Senior physician
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Department of Anesthesiology and Intensive Care Medicine, Dresden, Saxony, Germany
Dresden, Sachsen, Germany
OT

Oliver Tiebel

Associate director
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Institute of Clinical Chemistry, Dresden, Saxony, Germany
Dresden, Sachsen, Germany
Jan Beyer-Westendorf, MD,PhD

Head of Division "Thrombosis and Hemostasis", Head of „Thrombosis Research“
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Division of Hematology and Hemostasis, Department of Medicine I Thrombosis Research, Dresden, Saxony, Germany
Dresden, Sachsen, Germany
BR

Bertold Renner

Deputy director
Institute of Clinical Pharmacology, Faculty of Medicine „Carl Gustav Carus“, Technische Universität Dresden, Dresden, Germany
Dresden, Sachsen, Germany
TK

Thea Koch

Head of department
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Department of Anesthesiology and Intensive Care Medicine, Dresden, Saxony, Germany
Dresden, Sachsen, Germany
PS

Peter Spieth

Deputy director
University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Department of Anesthesiology and Intensive Care Medicine, Dresden, Saxony, Germany
Dresden, Sachsen, Germany

Background: Argatroban is indicated for treatment of heparin-induced thrombocytopenia, but is also used in critical ill COVID-19 patients presenting with extensive thrombin overload. Direct drug monitoring is not available and argatroban dosing is mainly based on activated partial plasmin time (aPTT), which has limitations in hypercoagulable patients with increased FVIII.

Aims: The aim of this study was to compare correlation of routine clotting tests (aPTT, ecarin clotting time [ECA-CT] and diluted thrombin time [dTT]) to argatroban plasma levels measured by gold standard mass spectrometry (LC/MS/MS).

Methods: From 06/2021 to 03/2022, 205 samples from 22 COVID-19 ICU patients were analyzed: aPTT and dTT on STA R Max3-Analyzer (Stago Deutschland GmbH, Germany) using the BIOPHEN® DTI Kit with Argatroban-calibration (CoaChrom Diagnostica GmbH, Austria); ECA-CT was measured using ClotPro® ecarin assay. LC/MS/MS was performed using an RP column, a solvent gradient and an API4000 mass spectrometer with electrospray. Correlation was analyzed using Pearson correlation coefficient r in R version 3.2.4. This study was approved by the Ethics Committee of the Technical University of Dresden, Germany (BO-EK-64022022) and registered with German Clinical Trials Register DRKS00028689.

Results: Form 205 samples with LC/MS/MS analysis, 195 were compared to aPTT, 153 to ECA-CT and 105 to dTT. In 40 samples, dTT was not measureable due high bilirubin values. Compared to LC/MS/MS, correlation of dTT was highest (r =0.924), followed by ECA-CT (r 0.609) and aPTT (r 0.367; p< 0.001; FIGURE 1). When recommended cut-offs for argatroban plasma levels (500-1000 ng/ml according to SmPC) were applied, dTT (when measurable) and ECA-CT better identified critical values of argatroban plasma values >1000ng/ml than aPTT (FIGURE 2).

Conclusion(s): Argatroban in critical ill COVID-19 patients should be monitored using dTT. If dTT is not possible or measurements are highly time-sensitive, point-of-care ClotPro® ECA-test should be preferably used instead of aPTT.