Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross‐sectional pharmacodynamic study based on peak and trough plasma levels
2013; Elsevier BV; Volume: 11; Issue: 8 Linguagem: Inglês
10.1111/jth.12308
ISSN1538-7933
AutoresE. M. Hawes, Allison M. Deal, D. Funk‐Adcock, Robert C. Gosselin, C. Jeanneret, Abigail Cook, Jeff Taylor, Herbert C. Whinna, Anne Winkler, Stephan Moll,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoJournal of Thrombosis and HaemostasisVolume 11, Issue 8 p. 1493-1502 Original ArticleFree Access Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels E. M. Hawes, Corresponding Author E. M. Hawes Department of Pharmacy, School of Medicine, Department of Family Medicine, University of North Carolina, Chapel Hill, NC, USA Correspondence: Emily M. Hawes, Department of Family Medicine, University of North Carolina School of Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599, USA. Tel.: +1 919 843 8408; fax: +1 919 966 6125. E-mail: ehawes@unch.unc.eduSearch for more papers by this authorA. M. Deal, A. M. Deal Lineberger Comprehensive Cancer Center Biostatistics Core, Chapel Hill, NC, USASearch for more papers by this authorD. Funk-Adcock, D. Funk-Adcock Esoterix Inc., Englewood, CO, USASearch for more papers by this authorR. Gosselin, R. Gosselin Department of Pathology and Laboratory Medicine, University of California, Davis Health, Sacramento, CA, USASearch for more papers by this authorC. Jeanneret, C. Jeanneret Division of Hematology-Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this authorA. M. Cook, A. M. Cook Loyola University Health System, Maywood, IL, USASearch for more papers by this authorJ. M. Taylor, J. M. Taylor Esoterix Inc., Englewood, CO, USASearch for more papers by this authorH. C. Whinna, H. C. Whinna Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this authorA. M. Winkler, A. M. Winkler Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USASearch for more papers by this authorS. Moll, S. Moll Division of Hematology-Oncology, Department of Medicine, Hemophilia and Thrombosis Center, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this author E. M. Hawes, Corresponding Author E. M. Hawes Department of Pharmacy, School of Medicine, Department of Family Medicine, University of North Carolina, Chapel Hill, NC, USA Correspondence: Emily M. Hawes, Department of Family Medicine, University of North Carolina School of Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599, USA. Tel.: +1 919 843 8408; fax: +1 919 966 6125. E-mail: ehawes@unch.unc.eduSearch for more papers by this authorA. M. Deal, A. M. Deal Lineberger Comprehensive Cancer Center Biostatistics Core, Chapel Hill, NC, USASearch for more papers by this authorD. Funk-Adcock, D. Funk-Adcock Esoterix Inc., Englewood, CO, USASearch for more papers by this authorR. Gosselin, R. Gosselin Department of Pathology and Laboratory Medicine, University of California, Davis Health, Sacramento, CA, USASearch for more papers by this authorC. Jeanneret, C. Jeanneret Division of Hematology-Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this authorA. M. Cook, A. M. Cook Loyola University Health System, Maywood, IL, USASearch for more papers by this authorJ. M. Taylor, J. M. Taylor Esoterix Inc., Englewood, CO, USASearch for more papers by this authorH. C. Whinna, H. C. Whinna Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this authorA. M. Winkler, A. M. Winkler Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USASearch for more papers by this authorS. Moll, S. Moll Division of Hematology-Oncology, Department of Medicine, Hemophilia and Thrombosis Center, University of North Carolina School of Medicine, Chapel Hill, NC, USASearch for more papers by this author First published: 30 May 2013 https://doi.org/10.1111/jth.12308Citations: 162 Manuscript handled by: M. Cattaneo Final decision: F. R. Rosendaal, 22 May 2013 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Summary Background Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations. Objective To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect. Methods Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values. Results The therapeutic range was 27–411 ng mL−1. The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. Conclusions The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327). Introduction Although anticoagulation monitoring of patients on therapeutic doses of the new oral anticoagulant dabigatran is not routinely necessary, understanding of a patient's anticoagulation status may be desirable in certain clinical situations, such as when assessing for subtherapeutic or supratherapeutic levels when thromboembolic or hemorrhagic events occur, determining minimal residual drug effects prior to major surgery or thrombolytic therapy, or assessing the efficacy of reversal strategies when managing a patient with major bleeding. Limited information exists on the performance of coagulation tests in the determination of the level of anticoagulation in patients treated with therapeutic doses of dabigatran. Much of the existing information is derived from in vitro studies of dabigatran-spiked plasma, or ex vivo studies testing plasma samples from healthy volunteers who received various dabigatran doses 1-8. Information on ex vivo data from patients treated with dabigatran is limited, owing to the use of doses other than 150 mg twice daily, lack of reporting of detailed data, testing of only one reagent for a particular coagulation assay, and evaluation of coagulation response in patients enrolled into pharmaceutical company-sponsored studies with strict enrollment exclusion criteria 9-13. Very limited information exists on the performance of point-of-care (POC) coagulation assays in dabigatran-treated patients 1, 4, 14, 15. Professional medical organizations have developed guidelines detailing how to appropriately evaluate patients on the new oral anticoagulants with coagulation tests. However, recommendations have been made on the basis of limited data on test performance 13, 16-18. Given the potential need to assess anticoagulant status in certain patients, data on the performance of various coagulation assays in plasma and whole blood from actual patients treated with dabigatran are needed. The primary objective of this study was to determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect, by correlating the results of various coagulation assays with plasma drug levels in patients taking therapeutic doses of dabigatran. Patients and methods Patients The study was approved by the University of North Carolina (UNC) Institutional Review Board, and registered at www.clinicaltrials.gov as #NCT01588327. All 65 subjects provided written informed consent. Patients taking Food and Drug Administration-approved therapeutic doses of dabigatran at steady state receiving care at the UNC were eligible for inclusion. Volunteers who were not taking an anticoagulant were enrolled as controls. Methods For patients taking dabigatran, blood samples were obtained immediately prior to the next dabigatran dose (trough) and, on the same day, 2.5 h following the oral dosing (peak). A random blood sample was obtained for each control. For coagulation testing, blood samples were centrifuged at 1600 g for 15 min at 25 °C, spun again at 1600 g for 5 min to obtain platelet- poor plasma, aliquoted, and stored at − 70 °C until being analyzed. Whole blood samples obtained by venipuncture were added to disposable prothrombin time (PT), activated partial thromboplastin time (APTT) and activated clotting time-low range (ACT) cuvettes, and analyzed with the HEMOCHRON® (International Technidyne Corporation, Edison, NJ, USA) Signature Elite POC device. Table S1 contains a list of the reagents and devices used to perform the following tests: PT, APTT, ecarin chromogenic assay (ECA), ecarin clotting time (ECT), thrombin clotting time (TCT), ACT, and dilute thrombin time (dTT). Individual reagents and coagulation analyzers were used and operated according to the manufacturers' instructions. Plasma dabigatran levels were determined by liquid chromatography–mass spectrometry by Boehringer-Ingelheim in Biberach, Germany. Table 1. Summary of results for each coagulation test Test Reagent and device n Slope R 2 * ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. Predicted range† ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. Predicted trough range‡ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. Predicted peak range§ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. Normal reference range¶ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. MP** ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. (%) PT ratio HEMOCHRON® Signature Elite 1 67 0.0029 0.86 1.09–2.2 1.06–1.60 1.14–2.42 0.86–1.20 28 TriniCLOT™ PT HTF on MDA 2 69 0.0015 0.60 1.06–1.63 1.05–1.33 1.09–1.74 0.89–1.06 13 HemosIL® RecombiPlasTin 2G on ACL TOP 700 (UNC) 3 69 0.0011 0.66 1.05–1.46 1.04–1.24 1.07–1.54 0.74–1.10 29 HemosIL® RecombiPlasTin 2G on ACL TOP 700 (UCDMC) 4 69 0.0011 0.62 1.05–1.46 1.04–1.24 1.07–1.54 0.86–1.14 43 Innovin® on Sysmex® CS-2000i System 5 69 0.0010 0.79 1.03–1.39 1.02–1.20 1.05–1.47 0.89–1.07 24 Innovin® on BCS® XP System 6 69 0.0009 0.75 1.03–1.38 1.02–1.19 1.05–1.45 0.87–1.08 39 APTT ratio†† ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. Dade® Actin® on Sysmex® CS-2000i System 1 69 0.063 0.77 1.28–2.23 1.22–1.86 1.37–2.34 0.80–1.26 19 HemosIL® SynthASil on ACL TOP 700 (UNC) 2 69 0.059 0.81 1.27–2.16 1.21–1.81 1.36–2.27 0.82–1.35 26 HemosIL® SynthASil on ACL TOP 700 (UCDMC) 3 69 0.059 0.78 1.27–2.15 1.21–1.80 1.35–2.25 0.86–1.19 11 HEMOCHRON® Signature Elite 4 67 0.057 0.75 1.26–2.12 1.21–1.78 1.35–2.22 0.52–1.32 19 Dade® Actin® FS on BCS® XP System 5 69 0.056 0.82 1.24–2.09 1.19–1.76 1.33–2.19 0.90–1.21 11 TriniCLOT™ automated aPTT on MDA 6 69 0.052 0.74 1.24–2.02 1.19–1.71 1.31–2.12 0.86–1.28 23 Dade® Actin® FSL on Sysmex® CS-2000i System 7 69 0.044 0.79 1.20–1.86 1.16–1.60 1.27–1.94 0.89–1.19 16 ACT HEMOCHRON® Signature Elite 67 0.311 0.71 155–275 152–211 161–298 99–180 40 TCT ratio HemosIL® Thrombin Time on ACL TOP 700 1 41‡‡ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. 0.137 0.97 4.73–57.2 3.47–29.2 7.16–67.6 0.76–1.18 0 Pacific Hemostasis® Thrombin on Diagnostica Stago STart 4 Hemostasis Analyzer 2 40‡‡ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. 0.09 0.75 3.37–37.7 2.54–19.3 4.96–44.5 0.83–1.23 0 ECA (ng mL−1) ECA-T on BCS® XP System 1 69 0.917 0.99 24.0–376 15.6–188 40.3–445 §§ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. 0 ECA-T on Stago STA Compact 2 69 0.764 0.94 48.8–342 41.8–185 62.4–400 §§ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. 8.6 ECA-T on Diagnostica Stago STA-R Evolution® 3 69 0.685 0.95 34.4–297 28.1–157 46.6–349 §§ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the assay's lower limit of detection. 0 ECT ECARIN Prothrombin Activator on Diagnostica Stago STart 4 Hemostasis Analyzer 69 0.322 0.98 34.7–158 31.7–92.2 40.4–183 22.0–26.8 0 dTT Hemoclot® Thrombin Inhibitor on BCS® XP System 67 0.711 0.92 35.7–306 29.2–161 48.2–359 §§ ACT, activated clotting time; APTT, activated partial thromboplastin time; dTT, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; MP, misprediction; n, number of individual samples analyzed; PT, prothrombin time; TCT, thrombin clotting time; UCDMC, University of California Davis Health System; UNC, University of North Carolina. *The R-squared (R2) value is the square of the correlation coefficient. †The predicted range comprises the predicted test values for the therapeutic dabigatran range based on the fitted line. ‡The predicted trough range comprises the predicted test values for the therapeutic dabigatran range at trough. §The predicted peak range comprises the predicted test values for the therapeutic dabigatran range at peak. ¶The normal reference range represents the range of coagulation test results for all control participants. **The percentage of MP represents how often the coagulation test values were in the normal reference range while the plasma dabigatran concentration was in the therapeutic range. ††For APTT ratio, curves were fitted, and the slope can be considered to be scale parameter. The form of these curves are . ‡‡Excludes unmeasurable TCT results. §§Below the
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