Laboratory Assessment of Direct Oral Anticoagulants

Seminars in Thrombosis and Hemostasis

Volumn 43, Issue 3, 2017, Pages 277-290

  Douxfils, Jonathan ^a   Gosselin, Robert C ^b  

^a University of Namur   (Belgium)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

activated partial thromboplastin time; anti Xa; apixaban; dabigatran; dilute thrombin time; Ecarin; edoxaban; prothrombin time; rivaroxaban

Indexed keywords

ANTICOAGULANT AGENT; VITAMIN K GROUP; WARFARIN;

ANTICOAGULANT THERAPY; ARTICLE; DRUG BLOOD LEVEL; HUMAN; LABORATORY TEST; MASS SPECTROMETRY; PRIORITY JOURNAL; PROTHROMBIN TIME; THROMBIN TIME; ANTAGONISTS AND INHIBITORS; BLOOD; BLOOD CLOTTING; BLOOD CLOTTING TEST; DRUG EFFECTS; DRUG MONITORING; ORAL DRUG ADMINISTRATION; POINT OF CARE SYSTEM; PROCEDURES; TANDEM MASS SPECTROMETRY;

ADMINISTRATION, ORAL; ANTICOAGULANTS; BLOOD COAGULATION; BLOOD COAGULATION TESTS; DRUG MONITORING; HUMANS; POINT-OF-CARE SYSTEMS; TANDEM MASS SPECTROMETRY; VITAMIN K; WARFARIN;

EID: 85014112017     PISSN: 00946176     EISSN: 10989064     Source Type: Journal    
DOI: 10.1055/s-0036-1597296     Document Type: Article

References (118)

1. Ageno W Gallus A S Wittkowsky A Crowther M Hylek E M Palareti G; American College of Chest Physicians. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012 141 (2, Suppl): e44S 88S
2. Schulman S Wåhlander K Lundström T Clason S B Eriksson H; THRIVE III Investigators. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran N Engl J Med 2003 349 18 1713 1721
3. Albers G W Diener H C Frison L, et al; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial JAMA 2005 293 6 690 698
4. European Medicines Agency-Pradaxa-Procedure EMEA/H/C/829 Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000829/WC500041062.pdf. Accessed February 28, 2017
5. Food and Drug Administration Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm [News release of FDA approval of dabigatran for use in patients with atrial fibrillation] October 19, 2010
6. Bauersachs R Berkowitz S D Brenner B, et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism N Engl J Med 2010 363 26 2499 2510
7. Lassen M R Raskob G E Gallus A Pineo G Chen D Portman R J Apixaban or enoxaparin for thromboprophylaxis after knee replacement N Engl J Med 2009 361 6 594 604 [Erratum in N Engl J Med 2009;361(18):1814]
8. Giugliano R P Ruff C T Braunwald E, et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation N Engl J Med 2013 369 22 2093 2104
9. van Ryn J Stangier J Haertter S, et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity Thromb Haemost 2010 103 6 1116 1127
10. Douxfils J Mullier F Robert S Chatelain C Chatelain B Dogné J M Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate Thromb Haemost 2012 107 5 985 997
11. Mani H Hesse C Stratmann G Lindhoff-Last E Rivaroxaban differentially influences ex vivo global coagulation assays based on the administration time Thromb Haemost 2011 106 1 156 164
12. Douxfils J Chatelain C Chatelain B Dogné J M Mullier F Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide Thromb Haemost 2013 110 2 283 294
13. Baglin T Keeling D Kitchen S; British Committee for Standards in Haematology. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: guidance from the British Committee for Standards in Haematology Br J Haematol 2012 159 4 427 429
14. Harenberg J Marx S Weiss C Krämer R Samama M Schulman S; Subcommittee on Control of Anticoagulation of the ISTH. Report of the Subcommittee of Control of Anticoagulation on the determination of the anticoagulant effects of rivaroxaban J Thromb Haemost 2012 10 7 1433 1436
15. Gosselin R C Adcock D Hawes E M Francart S J Grant R P Moll S Evaluating the use of commercial drug-specific calibrators for determining PT and APTT reagent sensitivity to dabigatran and rivaroxaban Thromb Haemost 2015 113 1 77 84
16. Bloemen S De Laat M De Laat B Hemker H C Al Dieri R Will one size of anticoagulant dosage fit all? Drug Dev Res 2013 74 7 406 412
17. Ten Cate H New oral anticoagulants: discussion on monitoring and adherence should start now! Thromb J 2013 11 1 8
18. Douxfils J Mullier F Dogné J M Dose tailoring of dabigatran etexilate: obvious or excessive? Expert Opin Drug Saf 2015 14 8 1283 1289
19. European Medicines Agency Xarelto-Summary of Product Characteristics Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf. Accessed February 6, 2017
20. European Medicines Agency Pradaxa-Summary of Product Characteristics Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000829/WC500041060.pdf. Accessed February 6, 2017
21. European Medicines Agency Eliquis-Summary of Product Characteristics Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. Accessed February 6, 2017
22. European Medicines Agency Lixiana - Summary of Product Characteristics Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002629/WC500189048.pdf. Accessed February 6, 2017
23. Food and Drug Administration Pradaxa - Prescribing Information Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022512s018lbl.pdf. Accessed February 6, 2017
24. Food and Drug Administration Xarelto - Prescribing Information Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202439s001lbl.pdf. Accessed February 6, 2017
25. Food and Drug Administration Eliquis - Prescribing Information Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf. Accessed February 6, 2017
26. Food and Drug Administration Savaysa - Prescribing Information Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf. Accessed February 6, 2017
27. Nutescu E Chuatrisorn I Hellenbart E Drug and dietary interactions of warfarin and novel oral anticoagulants: an update J Thromb Thrombolysis 2011 31 3 326 343
28. Liesenfeld K H Lehr T Dansirikul C, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial J Thromb Haemost 2011 9 11 2168 2175
29. Leil T A Frost C Wang X Pfister M LaCreta F Model-based exposure-response analysis of apixaban to quantify bleeding risk in special populations of subjects undergoing orthopedic surgery CPT Pharmacometrics Syst Pharmacol 2014 3 e136
30. Mueck W Stampfuss J Kubitza D Becka M Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban Clin Pharmacokinet 2014 53 1 1 16
31. Mismetti P Laporte S New oral antithrombotics: a need for laboratory monitoring. For J Thromb Haemost 2010 8 4 621 626
32. Ten Cate H Monitoring new oral anticoagulants, managing thrombosis, or both? Thromb Haemost 2012 107 5 803 805
33. Food and Drug Administration Xarelto-Clinical Pharmacology and Biopharmaceutics Review(s) Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022406Orig1s000TOC.cfm. Accessed February 6, 2017
34. Food and Drug Administration Eliquis-Clinical Pharmacology and Biopharmaceutics Review(s) Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202155Orig1s002Approv.pdf. Accessed February 6, 2017
35. Paré G Eriksson N Lehr T, et al. Genetic determinants of dabigatran plasma levels and their relation to bleeding Circulation 2013 127 13 1404 1412
36. Reilly P A Lehr T Haertter S, et al; RE-LY Investigators. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) J Am Coll Cardiol 2014 63 4 321 328
37. Ruff C T Giugliano R P Braunwald E, et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial Lancet 2015 385 (9984): 2288 2295
38. Weitz J I Connolly S J Patel I, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation Thromb Haemost 2010 104 3 633 641
39. European Medicines Agency Pradaxa-EMEA/H/C/000829/X/13/G Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000829/WC500110875.pdf. Accessed July 16, 2016.
40. Godier A Martin A C Leblanc I, et al. Peri-procedural management of dabigatran and rivaroxaban: duration of anticoagulant discontinuation and drug concentrations Thromb Res 2015 136 4 763 768
41. Pernod G Comments on: Laboratory tests for the management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants: proposals of the Working Group on Perioperative Haemostasis (GIHP): a rebuttal Arch Cardiovasc Dis 2014 107 5 346 347
42. Tripodi A Di Minno D Moia M Comments on: Laboratory tests for the management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants: proposals of the Working Group on Perioperative Haemostasis (GIHP) Arch Cardiovasc Dis 2014 107 5 345 346
43. Pernod G Albaladejo P Godier A, et al; Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP)-March 2013 Arch Cardiovasc Dis 2013 106 (6-7): 382 393
44. Levy J H Ageno W Chan N C Crowther M Verhamme P Weitz J I; Subcommittee on Control of Anticoagulation. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH J Thromb Haemost 2016 14 3 623 627
45. Lip G Y Windecker S Huber K, et al; Document Reviewers. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS) Eur Heart J 2014 35 45 3155 3179
46. Verhamme P Wells P S Segers A, et al. Dose reduction of edoxaban preserves efficacy and safety for the treatment of venous thromboembolism. An analysis of the randomised, double-blind HOKUSAI VTE trial Thromb Haemost 2016 116 747 753
47. Schmitz E M Boonen K van den Heuvel D J, et al. Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants J Thromb Haemost 2014 12 10 1636 1646
48. Gous T Couchman L Patel J P Paradzai C Arya R Flanagan R J Measurement of the direct oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma using turbulent flow liquid chromatography with high-resolution mass spectrometry Ther Drug Monit 2014 36 5 597 605
49. Rohde G Determination of rivaroxaban--a novel, oral, direct Factor Xa inhibitor--in human plasma by high-performance liquid chromatography-tandem mass spectrometry J Chromatogr B Analyt Technol Biomed Life Sci 2008 872 (1-2): 43 50
50. Lessire S Douxfils J Baudar J, et al. Is thrombin time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study Thromb Res 2015 136 3 693 696
51. Kubitza D Becka M Wensing G Voith B Zuehlsdorf M Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--after multiple dosing in healthy male subjects Eur J Clin Pharmacol 2005 61 12 873 880
52. Stangier J Rathgen K Stähle H Gansser D Roth W The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects Br J Clin Pharmacol 2007 64 3 292 303
53. Barrett Y C Wang J Song Y, et al. A randomised assessment of the pharmacokinetic, pharmacodynamic and safety interaction between apixaban and enoxaparin in healthy subjects Thromb Haemost 2012 107 5 916 924
54. Bathala M S Masumoto H Oguma T He L Lowrie C Mendell J Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans Drug Metab Dispos 2012 40 12 2250 2255
55. Delavenne X Mismetti P Basset T Rapid determination of apixaban concentration in human plasma by liquid chromatography/tandem mass spectrometry: application to pharmacokinetic study J Pharm Biomed Anal 2013 78-79 150 153
56. Douxfils J Dogné J M Mullier F, et al. Comparison of calibrated dilute thrombin time and aPTT tests with LC-MS/MS for the therapeutic monitoring of patients treated with dabigatran etexilate Thromb Haemost 2013 110 3 543 549
57. Douxfils J Tamigniau A Chatelain B, et al. Comparison of calibrated chromogenic anti-Xa assay and PT tests with LC-MS/MS for the therapeutic monitoring of patients treated with rivaroxaban Thromb Haemost 2013 110 4 723 731
58. Antovic J P Skeppholm M Eintrei J, et al. Evaluation of coagulation assays versus LC-MS/MS for determinations of dabigatran concentrations in plasma Eur J Clin Pharmacol 2013 69 11 1875 1881
59. Skeppholm M Hjemdahl P Antovic J P, et al. On the monitoring of dabigatran treatment in “real life” patients with atrial fibrillation Thromb Res 2014 134 4 783 789
60. Skeppholm M Al-Aieshy F Berndtsson M, et al. Clinical evaluation of laboratory methods to monitor apixaban treatment in patients with atrial fibrillation Thromb Res 2015 136 1 148 153
61. Vogeser M Seger C Pitfalls associated with the use of liquid chromatography-tandem mass spectrometry in the clinical laboratory Clin Chem 2010 56 8 1234 1244
62. Clarke W Rhea J M Molinaro R Challenges in implementing clinical liquid chromatography-tandem mass spectrometry methods--the light at the end of the tunnel J Mass Spectrom 2013 48 7 755 767
63. Annesley T Majzoub J Hsing A Wu A Rockwood A Mason D Mass spectrometry in the clinical laboratory: how have we done, and where do we need to be? Clin Chem 2009 55 6 1236 1239
64. Hawes E M Deal A M Funk-Adcock D, et al. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels J Thromb Haemost 2013 11 8 1493 1502
65. Gosselin R C Adcock D M The laboratory's 2015 perspective on direct oral anticoagulant testing J Thromb Haemost 2016 14 5 886 893
66. Pollack C V Jr Reilly P A Bernstein R, et al. Design and rationale for RE-VERSE AD: a phase 3 study of idarucizumab, a specific reversal agent for dabigatran Thromb Haemost 2015 114 1 198 205
67. Dager W E Gosselin R C Kitchen S Dwyre D Dabigatran effects on the international normalized ratio, activated partial thromboplastin time, thrombin time, and fibrinogen: a multicenter, in vitro study Ann Pharmacother 2012 46 12 1627 1636
68. Adcock D M Gosselin R Direct oral anticoagulants (DOACs) in the laboratory: 2015 review Thromb Res 2015 136 1 7 12
69. Bonar R Favaloro E J Mohammed S Pasalic L Sioufi J Marsden K The effect of dabigatran on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples Pathology 2015 47 4 355 364
70. Douxfils J Lessire S Dincq A S, et al. Estimation of dabigatran plasma concentrations in the perioperative setting. An ex vivo study using dedicated coagulation assays Thromb Haemost 2015 113 4 862 869
71. Stangier J Feuring M Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran Blood Coagul Fibrinolysis 2012 23 2 138 143
72. Avecilla S T Ferrell C Chandler W L Reyes M Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy Am J Clin Pathol 2012 137 4 572 574
73. Gosselin R Hawes E Moll S Adcock D Performance of various laboratory assays in the measurement of dabigatran in patients receiving therapeutic doses: a prospective study based on peak and trough plasma levels Am J Clin Pathol 2014 141 2 262 267
74. Gosselin R C Dwyre D M Dager W E Measuring dabigatran concentrations using a chromogenic ecarin clotting time assay Ann Pharmacother 2013 47 12 1635 1640
75. Mueck W Borris L C Dahl O E, et al. Population pharmacokinetics and pharmacodynamics of once-and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement Thromb Haemost 2008 100 3 453 461
76. Mueck W Eriksson B I Bauer K A, et al. Population pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor--in patients undergoing major orthopaedic surgery Clin Pharmacokinet 2008 47 3 203 216
77. Barrett Y C Wang Z Frost C Shenker A Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay Thromb Haemost 2010 104 6 1263 1271
78. Samama M M Martinoli J L LeFlem L, et al. Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor Thromb Haemost 2010 103 4 815 825
79. Hillarp A Baghaei F Fagerberg Blixter I, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays J Thromb Haemost 2011 9 1 133 139
80. Douxfils J Mullier F Loosen C Chatelain C Chatelain B Dogné J M Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendations for the monitoring of rivaroxaban and review of the literature Thromb Res 2012 130 6 956 966
81. Van Blerk M Bailleul E Chatelain B, et al. Influence of dabigatran and rivaroxaban on routine coagulation assays. A nationwide Belgian survey Thromb Haemost 2015 113 1 154 164
82. Douxfils J Chatelain B Chatelain C Dogné J M Mullier F Edoxaban: impact on routine and specific coagulation assays. A practical laboratory guide Thromb Haemost 2016 115 2 368 381
83. Becker R C Alexander J H Newby L K, et al. Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome Thromb Haemost 2010 104 5 976 983
84. Frost C Nepal S Wang J, et al. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects Br J Clin Pharmacol 2013 76 5 776 786
85. Douxfils J Pochet L Lessire S, et al. Mass spectrometry in the therapeutic drug monitoring of direct oral anticoagulants. Useful or useless? TrAC Trends in Analytical Chemistry 2016 84 (Part B): 41 50
86. Harenberg J Du S Weiss C Krämer R Hoppensteadt D Walenga J; working party: methods to determine apixaban of the Subcommittee on Control of Anticoagulation of the International Society of Thrombosis and Haemostasis. Report of the Subcommittee on Control of Anticoagulation on the determination of the anticoagulant effects of apixaban: communication from the SSC of the ISTH J Thromb Haemost 2014 12 5 801 804
87. Douxfils J Legrand H Sennesael A L, et al. CA54: Matrix effect of commercially available direct oral anticoagulant standards: a look through the limits and the need for standardization of current calibrators J Thromb Haemost 2016 14 01 31
88. Francart S J Hawes E M Deal A M, et al. Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels Thromb Haemost 2014 111 6 1133 1140
89. Becker R C Yang H Barrett Y, et al. Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor J Thromb Thrombolysis 2011 32 2 183 187
90. Douxfils J Chatelain B Hjemdahl P, et al. Does the Russell viper venom time test provide a rapid estimation of the intensity of oral anticoagulation? A cohort study Thromb Res 2015 135 5 852 860
91. Gosselin R C Adcock Funk D M Taylor J M, et al. Comparison of anti-Xa and dilute Russell viper venom time assays in quantifying drug levels in patients on therapeutic doses of rivaroxaban Arch Pathol Lab Med 2014 138 12 1680 1684
92. Hillarp A Gustafsson K M Faxälv L, et al. Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays J Thromb Haemost 2014 12 9 1545 1553
93. Mani H Hesse C Stratmann G Lindhoff-Last E Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions Thromb Haemost 2013 109 1 127 136
94. Lindhoff-Last E Samama M M Ortel T L Weitz J I Spiro T E Assays for measuring rivaroxaban: their suitability and limitations Ther Drug Monit 2010 32 6 673 679
95. Samama M M Amiral J Guinet C Perzborn E Depasse F An optimised, rapid chromogenic assay, specific for measuring direct factor Xa inhibitors (rivaroxaban) in plasma Thromb Haemost 2010 104 5 1078 1079
96. Samama M M Contant G Spiro T E, et al; Rivaroxaban Anti-Factor Xa Chromogenic Assay Field Trial Laboratories. Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls Thromb Haemost 2012 107 2 379 387
97. Samama M M Guinet C Le Flem L Ninin E Debue J M Measurement of dabigatran and rivaroxaban in primary prevention of venous thromboembolism in 106 patients, who have undergone major orthopedic surgery: an observational study J Thromb Thrombolysis 2013 35 2 140 146
98. Samama M M Mendell J Guinet C Le Flem L Kunitada S In vitro study of the anticoagulant effects of edoxaban and its effect on thrombin generation in comparison to fondaparinux Thromb Res 2012 129 4 e77 e82
99. Gouin-Thibault I Flaujac C Delavenne X, et al. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study Thromb Haemost 2014 111 2 240 248
100. Douxfils J Tamigniau A Chatelain B Goffinet C Dogné J M Mullier F Measurement of non-VKA oral anticoagulants versus classic ones: the appropriate use of hemostasis assays Thromb J 2014 12 24
101. Douxfils J Mani H Minet V, et al. Non-VKA oral anticoagulants: accurate measurement of plasma drug concentrations BioMed Res Int 2015 2015 345138
102. Mani H Rohde G Stratmann G, et al. Accurate determination of rivaroxaban levels requires different calibrator sets but not addition of antithrombin Thromb Haemost 2012 108 1 191 198
103. Gosselin R C Francart S J Hawes E M Moll S Dager W E Adcock D M Heparin-calibrated chromogenic anti-Xa activity measurements in patients receiving rivaroxaban: can this test be used to quantify drug level? Ann Pharmacother 2015 49 7 777 783
104. Exner T Ellwood L Rubie J Barancewicz A Testing for new oral anticoagulants with LA-resistant Russells viper venom reagents. An in vitro study Thromb Haemost 2013 109 4 762 765
105. Adcock D M Gosselin R Kitchen S Dwyre D M The effect of dabigatran on select specialty coagulation assays Am J Clin Pathol 2013 139 1 102 109
106. Dias J D Norem K Doorneweerd D D Thurer R L Popovsky M A Omert L A Use of thromboelastography (TEG) for detection of new oral anticoagulants Arch Pathol Lab Med 2015 139 5 665 673
107. Herrmann R Thom J Wood A Phillips M Muhammad S Baker R Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban Thromb Haemost 2014 111 5 989 995
108. Adelmann D Wiegele M Wohlgemuth R K, et al. Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry Thromb Res 2014 134 4 918 923
109. Chojnowski K Górski T Robak M Treliński J Effects of rivaroxaban therapy on ROTEM coagulation parameters in patients with venous thromboembolism Adv Clin Exp Med 2015 24 6 995 1000
110. Helin T A Lemponen M Hjemdahl P Rönquist-Nii Y Lassila R Joutsi-Korhonen L From laboratory to clinical practice: dabigatran effects on thrombin generation and coagulation in patient samples Thromb Res 2015 136 1 154 160
111. Freyburger G Macouillard G Labrouche S Sztark F Coagulation parameters in patients receiving dabigatran etexilate or rivaroxaban: two observational studies in patients undergoing total hip or total knee replacement Thromb Res 2011 127 5 457 465
112. Ebner M Peter A Spencer C, et al. Point-of-care testing of coagulation in patients treated with non-vitamin K antagonist oral anticoagulants Stroke 2015 46 10 2741 2747
113. Al-Aieshy F Malmström R E Antovic J, et al. Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation Eur J Clin Pharmacol 2016 72 6 671 679
114. Mani H Herth N Kasper A, et al. Point-of-care coagulation testing for assessment of the pharmacodynamic anticoagulant effect of direct oral anticoagulant Ther Drug Monit 2014 36 5 624 631
115. Lind S E Boyle M E Fisher S Ishimoto J Trujillo T C Kiser T H Comparison of the aPTT with alternative tests for monitoring direct thrombin inhibitors in patient samples Am J Clin Pathol 2014 141 5 665 674
116. Visino F Zaccaria F Semeraro N Colucci M A modified prothrombin time to measure the anticoagulant activity of dabigatran Thromb Res 2014 134 6 1368 1369
117. Letertre L R Gudmundsdottir B R Francis C W, et al. A single test to assay warfarin, dabigatran, rivaroxaban, apixaban, unfractionated heparin, and enoxaparin in plasma J Thromb Haemost 2016 14 5 1043 1053
118. Du S Weiss C Christina G, et al. Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods Clin Chem Lab Med 2015 53 8 1237 1247