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: Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2014.12.021
• Languages: English
• ISSNs: 0049-3848

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0075">Introduction</title> <p id="sp0005">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<sup>®</sup> 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<sup>®</sup> 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.</p> </sec> <sec> <title id="st0080">Materials and Methods</title> <p id="sp0010">Overall, 304 plasma samples were obtained from seven ESRD patients in dabigatran steady-state for measurement by HEMOCLOT<sup>®</sup> (calibrated diluted thrombin time [dTT]) and by LC-MS/MS. Agreement of dabigatran concentrations was assessed by regression analysis and difference plots.</p> </sec> <sec> <title id="st0085">Results</title> <p id="sp0015">The measurements of calibration standards of the HEMOCLOT<sup>®</sup> assay showed excellent precision with coefficients of variation < 5%. Accuracy determined by analysis of two quality control samples was 90% and 111%. HEMOCLOT<sup>®</sup>-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).</p> </sec> <sec> <title id="st0090">Conclusions</title> <p id="sp0020">The HEMOCLOT<sup>®</sup> 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<sup>®</sup> assay and the LC-MS/MS reference method met bioanalytical acceptance criteria.</p> </sec> </abstract>