Measurement of dabigatran: previously demonstrated Hemoclot^® Thrombin Inhibitor assay reagent instability on Sysmex CS-2100i is no longer an issue

Abstract

The Hemoclot^® Thrombin Inhibitor (HTI) assay has been recommended for measurement of dabigatran concentrations in specific clinical situations. Traditionally, reagents for biochemical assays are prepared from instructions found in the package insert. For the HTI reagents the manufacturer recommends incubating the reagents much longer than indicated in the package insert. These recommendations are added to the application sheets designed for different analyzers. Many clinicians and laboratory personnel may be unaware of the discrepancy between the two instructions, resulting in incorrect handling of the reagents. The aim of this study was to investigate the effect of the two different preparation methods on reagent stability and test results. For the standard concentration range, reagent stability on Sysmex CS-2100i was only two hours instead of the eight hours indicated by the producer when following package insert instructions (incubation time: 15 min). Stability was increased to five hours when following the application sheet (incubation time: 60 min). Two years later, the study was repeated using samples of patients treated with dabigatran etexilate. This time, reagent stability was at least six hours. Since the reagent composition was unchanged, the increased stability could be due to changed logistics by the supplier, with stock and transfer closer by. Previously demonstrated HTI reagent instability is no longer an issue at our laboratory. The reliability of results of clinical studies in which the assay has been used is potentially compromised.

Keywords:

• Dabigatran
• hematologic tests
• thrombin time
• antidotes
• anticoagulants
• atrial fibrillation
• laboratories

Disclosure statement

A 15% research discount was received from ANIARA on all HTI reagents, calibrators and controls used in this study. Conflicts of interest not directly related to this manuscript: W. J. Comuth has received research support from the European Society of Cardiology Working Group on Thrombosis, Siemens Healthcare and Diagnostica Stago; personal and/or speaker fees from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer and Astra-Zeneca; and she is principle investigator for studies conducted by Thrombosis Research Institute, Boehringer Ingelheim and Janssens-Cilag A/S. A.-M. B. Münster has received speaker fees from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer and Merck Sharp & Dohme Corporation (MSD). L. Faaborg and L. Ø. Henriksen have no conflicts of interest.