Measurement of dabigatran plasma concentrations by calibrated thrombin clotting time in comparison to LC-MS/MS in human volunteers on dialysis. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Schmohl, Michael; Gansser, Dietmar; Moschetti, Viktoria; Stangier, Joachim
• Is Part Of: Thrombosis research. Volume 135:Issue 3(2015)
• Page Start: 532
• Page End: 536
• Publication Date: 2015-03
• Subjects: aPTT activated partial thromboplastin time -- CI confidence interval -- CV coefficient of variation -- DTI direct thrombin inhibitor -- dTT diluted thrombin time -- ECT ecarin clotting time -- EDTA ethylenediaminetetraacetic acid -- ESRD end-stage renal disease -- HD haemodialysis -- INR international normalised ratio -- LC-MS/MS liquid chromatography/tandem mass spectrometry -- PD pharmacodynamic(s) -- PK pharmacokinetic(s) -- PT prothrombin time -- QC quality control -- TT thrombin time -- VKA vitamin K antagonist; Method comparison -- Dabigatran etexilate -- Diluted thrombin time -- HEMOCLOT® Thrombin Inhibitors assay -- LC-MS/MS -- end-stage renal disease; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2014.12.021
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Dabigatran etexilate is an oral direct thrombin inhibitor. Although routine anticoagulation monitoring with dabigatran is not usually required, a simple and precise laboratory test to measure dabigatran concentrations in patient plasma may be useful in certain clinical circumstances, such as emergency situations. The HEMOCLOT ® Thrombin Inhibitors assay has demonstrated accurate and precise determination of dabigatran concentrations within a range of 50–500 ng/ml. The objective of this study was to assess comparability of dabigatran concentrations determined by HEMOCLOT ® and by liquid chromatography/tandem mass spectrometry (LC-MS/MS) in plasma samples from human volunteers with end-stage renal disease (ESRD) undergoing regular haemodialysis (HD) during a Phase I study. Materials and Methods: Overall, 304 plasma samples were obtained from seven ESRD patients in dabigatran steady-state for measurement by HEMOCLOT ® (calibrated diluted thrombin time [dTT]) and by LC-MS/MS. Agreement of dabigatran concentrations was assessed by regression analysis and difference plots. Results: The measurements of calibration standards of the HEMOCLOT ® assay showed excellent precision with coefficients of variation < 5%. Accuracy determined by analysis of two quality control samples was 90% and 111%. HEMOCLOT ® -derived dabigatran plasma concentrations paralleled those obtained by LC-MS/MS. The mean ratio of the LC-MS/MS and dTT-derived concentrations was 0.955 (67% limits of agreement: 0.771–1.18). Conclusions: The HEMOCLOT ® Thrombin Inhibitors assay is suitable for measuring dabigatran plasma concentrations in volunteers with ESRD undergoing haemodialysis. The agreement between dabigatran concentrations determined by the HEMOCLOT ® assay and the LC-MS/MS reference method met bioanalytical acceptance criteria. Highlights: Comparison of dabigatran concentrations determined by HEMOCLOT ® dTT and LC-MS/MS. Samples were obtained from end-stage renal disease patients on haemodialysis. HEMOCLOT ® -dTT derived dabigatran concentrations paralleled those from LC-MS/MS. The dTT assay is suitable for measuring plasma dabigatran in this population.