Direct oral anticoagulants (DOACs): From the laboratory point of view

1. J. Carré, G. Jourdi, N. Gendron, D. Helley, P. Gaussem and L. Darnige, Recent advances in anticoagulant treatment of immune thrombosis: A focus on direct oral anticoagulants in heparin-induced thrombocytopenia and anti-phospholipid syndrome, Int. J. Mol. Sci. 23(1) (2022) Article ID 93; https://doi.org/10.3390/ijms23010093 Search in Google Scholar

2. T. Helin, Laboratory Monitoring of Direct Oral Anticoagulants (PhD thesis), University of Helsinki, Medical Faculty, Helsinki 2017. Search in Google Scholar

3. J. W. Skelley, A. R. Thomason and J. C. Nolen, Betrixaban (Bevyxxa): A direct-acting oral anticoagulant factor Xa inhibitor, Pharm. Ther. 43(2) (2018) 85–120. Search in Google Scholar

4. C. Dunois, Laboratory monitoring of direct oral anticoagulants (DOACs), Biomedicines 9 (2021) Article ID 445 (15 pages); https://doi.org/10.3390/biomedicines9050445 Search in Google Scholar

5. B. I. Eriksson, O. E. Dahl, L. Ahnfelt, P. Kälebo, J. Stangier, G. Nehmiz, K. Hermansson and V. Kohlbrenner, Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I, J. Thromb. Haemost. 2(9) (2004) 1573–1580; https://doi.org/10.1111/j.1538-7836.2004.00890.x Search in Google Scholar

6. B. I. Eriksson, O. E. Dahl, H. R. Buller, R. Hettiarachchi, N. Rosencher, M. L. Bravo, L. Ahnfelt, F. Piovella, J. Stangier, P. Kälebo and P. Reilly (BISTRO II study group), A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial, J. Thromb. Haemost. 3(1) (2005) 103–111; https://doi.org/10.1111/j.1538-7836.2004.01100.x Search in Google Scholar

7. L. Wallentin, S. Yusuf, M. D. Ezekowitz, M. Alings, M. Flather, M. G. Franzosi, P. Pais, A. Dans, J. Eikelboom, J. Oldgren, J. Pogue, P. A. Reilly, S. Yang and S. J. Connolly (RE-LY investigators), Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial, Lancet 376(9745) (2010) 975–983; https://doi.org/10.1016/S0140-6736(10)61194-4 Search in Google Scholar

8. C. B. Granger, J. H. Alexander, J. J. McMurray, R. D. Lopes, E. M. Hylek, M. Hanna, H. R. Al-Khalidi, J. Ansell, D. Atar, A. Avezum, M. C. Bahit, R. Diaz, J. D. Easton, J. A. Ezekowitz, G. Flaker, D. Garcia, M. Geraldes, B. J. Gersh, S. Golitsyn, S. Goto, A. G. Hermosillo, S. H. Hohnloser, J. Horowitz, P. Mohan, P. Jansky, B. S. Lewis, J. L. Lopez-Sendon, P. Pais, A. Parkhomenko, F. W. Verheugt, J. Zhu and L. Wallentin (ARISTOTLE committees and investigators), Apixaban versus warfarin in patients with atrial fibrillation, N. Engl. J. Med. 365(11) (2011) 981–992; https://doi.org/doi:10.1056/NEJMoa1107039 Search in Google Scholar

9. M. R. Patel, K. W. Mahaffey, J. Garg, G. Pan, D. E. Singer, W. Hacke, G. Breithardt, J. L. Halperin, G. J. Hankey, J. P. Piccini, R. C. Becker, C. C. Nessel, J. F. Paolini, S. D. Berkowitz, K. A. A. Fox, R. M. Califf (+ROCKET AF steering committee, for the ROCKET AF investigators), Rivaroxaban versus warfarin in nonvalvular atrial fibrillation, N. Engl. J. Med. 365(10) (2011) 883–891; https://doi.org/10.1056/NEJMoa1009638 Search in Google Scholar

10. The EINSTEIN investigators, Oral rivaroxaban for symptomatic venous thromboembolism, N. Engl. J. Med. 363 (2010) 2499–2510; https://doi.org/10.1056/NEJMoa1007903R Search in Google Scholar

11. P. Giugliano, C.T. Ruff, E. Braunwald, S. A. Murphy, S. D. Wiviott, J. L. Halperin (+ENGAGE AFTIMI 48 investigators), Edoxaban versus warfarin in patients with atrial fibrillation, N. Engl. J. Med. 369 (2013) 2093–2104; https://doi.org/10.1056/NEJMoa1310907 Search in Google Scholar

12. J. Douxfils, D. M. Adcock, S. M. Bates, E. J. Favaloro, I. Gouin-Thibault, C. Guillermo, Y. Kawai, E. Lindhoff-Last, S. Kitchen and R. C. Gosselin, 2021 Update of the International Council for Standardization in Haematology. Recommendations for laboratory measurement of direct oral anticoagulants, Thromb. Haemost. 121(8) (2021) 1008–1020; https://doi.org/10.1055/a-1450-8178 Search in Google Scholar

13. J. Raymond, L. Imbert, T. Cousin, T. Duflot, R. Varin, J. Wils and F. Lamoureux, Pharmacogenetics of direct oral anticoagulants: A systematic review, J. Pers. Med. 11(1) (2021) Article ID 37 (11 pages); https://doi.org/10.3390/jpm11010037 Search in Google Scholar

14. G. Grześk, D. Rogowicz, Ł. Wołowiec, A. Ratajczak, W. Gilewski and M. Chudzińska, The clinical significance of drug-food interactions of direct oral anticoagulants, Int. J. Mol. Sci. 22(16) (2021) Article ID 8531; https://doi.org/10.3390/ijms22168531 Search in Google Scholar

15. J. W. Eikelboom, D. J. Quinlan, J. Hirsh, S. J. Connolly and J. I. Weitz, Laboratory monitoring of non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation: A review, JAMA Cardiol. 2(5) (2017) 566–574; https://doi.org/10.1001/jamacardio.2017.0364 Search in Google Scholar

16. R. C. Gosselin, D. M. Adcock, S. M. Bates, J. Douxfils, E. J. Favaloro, I. Gouin-Thibault, C. Guillermo, Y. Kawai, E. Lindhoff-Last and S. Kitchen, International Council for Standardization in Haematology (ICSH). Recommendations for laboratory measurement of direct oral anticoagulants, Thromb. Haemost. 118(3) (2018) 437–450; https://doi.org/10.1055/s-0038-1627480 Search in Google Scholar

17. A. Tripodi, F. Marongiu, M. Moia, G. Palareti, V. Pengo, D. Poli, D. Prisco, S. Testa and M. Zanazzi, The vexed question of whether or not to measure levels of direct oral anticoagulants before surgery or invasive procedures, Intern. Emerg. Med. 13(7) (2018) 1029–1036; https://doi.org/10.1007/s11739-018-1854-6 Search in Google Scholar

18. M. S. Lim, K. Chapman, P. Swanepoel and A. K. Enjeti, Sensitivity of routine coagulation assays to direct oral anticoagulants: patient samples versus commercial drug-specific calibrators, Pathology 48(7) (2016) 712–719; https://doi.org/10.1016/j.pathol.2016.07.008 Search in Google Scholar

19. B. J. Dale, N. C. Chan and J. W. Eikelboom, Laboratory measurement of the direct oral anticoagulants, Br. J. Haematol. 172(3) (2016) 315–336; https://doi.org/10.1111/bjh.13810 Search in Google Scholar

20. European Medicines Agency, Pradaxa; Summary of Product Characteristics; EMA, Amsterdam, https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf, last access date April 04, 2022 Search in Google Scholar

21. M. Bridget and M. S. J. Kuehn, First oral blood thinner is approved for children, JAMA 326(7) (2021) Article ID 593; https://doi.org./10.1001/jama.2021.13259 Search in Google Scholar

22. J. Steffel, P. Verhamme, T. S. Potpara, P. Albaladejo, M. Antz, L. Desteghe, K. G. Haeusler, J. Oldgren, H. Reinecke, V. Roldan-Schilling, N. Rowell, P. Sinnaeve, R. Collins, A. J. Camm and H. Heidbüchel, The 2018 European Heart Rhythm Association Practical Guide on the use of nonvitamin K antagonist oral anticoagulants in patients with atrial fibrillation, Eur. Heart J. 39(16) (2018) 1330–1393; https://doi.org/10.1093/eurheartj/ehy136 Search in Google Scholar

23. J. Coates, E. Bitton, A. Hendje, T. Delate, K. L. Olson, C. Knowles, S. Ly, K. M. Fink and N. P. Clark, Clinical outcomes of dabigatran use in patients with non-valvular atrial fibrillation and weight > 120 kg, Thromb. Res. 208 (2021) 176–180; https://doi.org/10.1016/j.thromres.2021.11.007 Search in Google Scholar

24. European Medicines Agency, Xarelto; Summary of Product Characteristics, EMA, Amsterdam, https://www.ema.europa.eu/en/documents/product-information/xarelto-epar-product-information_en.pdf; last access date April 04, 2022 Search in Google Scholar

25. W. Mueck, J. Stampfuss, D. Kubitza and M. Becka, Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban, Clin. Pharmacokinet. 53 (2014) 1–16; https://doi.org/10.1007/s40262-013-0100-7 Search in Google Scholar

26. European Medicines Agency, Eliqius; Summary of Product Characteristics, https://www.ema.europa.eu/en/documents/product-information/eliquis-epar-product-information_en.pdf, last access date April 04, 2022 Search in Google Scholar

27. H. Mani and E. Lindhoff-Last, New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness, Drug Des. Devel. Ther. 8 (2014) 789–798; https://doi.org/10.2147/DDDT.S45644 Search in Google Scholar

28. S. H. Kanuri and R. P. Kreutz, Pharmacogenetics of bleeding and thromboembolic events in direct oral anticoagulant users, J. Pers. Med. 9(1) (2019) Article ID 7 (18 pages); https://doi.org/10.3390/jpm9010007 Search in Google Scholar

29. European Medicines Agency, Lixiana; Summary of Product Characteristics, https://www.ema.europa.eu/en/documents/product-information/lixiana-epar-product-information_en.pdf, last access date April 04, 2022 Search in Google Scholar

30. K. Ogata, J. Mendell-Harary, M. Tachibana, H. Masumoto, T. Oguma, M. Kojima and S. Kunitada, Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers, J. Clin. Pharmacol. 50(7) (2010) 743–753; https://doi.org/10.1177/0091270009351883 Search in Google Scholar

31. J. Steffel, R. Collins, M. Antz, P. Cornu, L. Desteghe, K. G. Haeusler, J. Oldgren, H. Reinecke, V. Roldan-Schilling, N. Rowell, P. T. Sinnaeve, T. Vanassche, T. Potpara, A. J. Camm and H. Heidbuchel, European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (EHRA practical guide), Europace 23(10) (2021) 1612–1676; https://doi.org/10.1093/europace/euab065 Search in Google Scholar

32. K. A. Martin, J. Beyer-Westendorf, B. L. Davidson, M. V. Huisman, P. M. Sandset and S. Moll, Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation, J. Thromb. Haemost. 19(8) (2021) 1874–1882; https://doi.org/10.1111/jth.15358 Search in Google Scholar

33. K. Deng, J. Cheng, S. Rao, H. Xu, L. Li and Y. Gao, Efficacy and safety of direct oral anticoagulants in elderly patients with atrial fibrillation: A network meta-analysis, Front. Med. (Laussane) 7 (2020) Article ID 107 (9 pages); https://doi.org/10.3389/fmed.2020.00107 Search in Google Scholar

34. H. S. Chun, R. Choe, M. Lee, Y. Cho, H. Y. Kim, K. Yoo and T. Hun Kim, Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis, Clin. Mol. Hepatol. 27 (2021) 535–552; https://doi.org/10.3350/cmh.2021.0109 Search in Google Scholar

35. J. H. Levy, W. Ageno, N. C. Chan, M. Crowther, P. Verhamme and J. I. Weitz (for 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. 14(3) (2016) 623–627; https://doi.org/10.1111/jth.13227 Search in Google Scholar

36. T. Steiner, M. Böhm, M. Dichgans, H. C. Diener, C. Ell, M. Endres, C. Epple, M. Grond, U. Laufs, G. Nickenig, H. Riess, J. Röther, P. D. Schellinger, M. Spannagl and R. Veltkamp, Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban, Clin. Res. Cardiol. 102 (2013) 399–412; https://doi.org/10.1007/s00392-013-0560-7 Search in Google Scholar

37. E. Rota, L. Testa, G. Di Brigida, S. Agosti, M. E. Rovere, R. Risso and N. Morelli, The management of patients with acute ischemic stroke while on direct oral anticoagulants (DOACs): data from an Italian cohort and a proposed algorithm, J. Thromb. Thrombolysis 50(3) (2020) 732–738; https://doi.org/10.1007/s11239-020-02108-5 Search in Google Scholar

38. J. D. Douketis, A. C. Spyropoulos, J. Duncan, M. Carrier, G. Le Gal, A. J. Tafur, T. Vanassche, P. Verhamme, S. Shivakumar, P. L. Gross, A. Y. Y. Lee, E. Yeo, S. Solymoss, J. Kassis, G. Le Templier, S. Kowalski, M. Blostein, V. Shah, E. MacKay, C. Wu, N. P. Clark, S. M. Bates, F. A. Spencer, E. Arnaoutoglou, M. Coppens, D. M. Arnold, J. A. Caprini, N. Li, K. A. Moffat, S. Syed and S. Schulman, Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant, JAMA Intern. Med. 179(11) (2019) 1469–1478; https://doi.org/10.1001/jamainternmed.2019.2431 Search in Google Scholar

39. J. D. Douketis, J. S. Healey, M. Brueckmann, J. W. Eikelboom, M. D. Ezekowitz, M. Fraessdorf, H. Noack J. Oldgren, P. Reilly, A. C. Spyropoulos, L. Wallentin and S. J. Connolly, Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure, Sub-study of the RE-LY trial, Thromb. Haemost. 113(3) (2015) 625–632; https://doi.org/10.1160/TH14-04-0305 Search in Google Scholar

40. J. R. Shaw, E. Kaplovitch and J. Douketis, Periprocedural menagement of oral anticoagulation, Med. Clin. N. Am. 104(4) (2020) 709–726; https://doi.org/10.1016/j.mcna.2020.02.005 Search in Google Scholar

41. A. Chen, E. Stecker and A. Warden, Direct oral anticoagulant use: a practical guide to common clinical challenges, Am. Heart Assoc. 9(13) (2020) e017559; https://doi.org/10.1161/JAHA.120.017559J Search in Google Scholar

42. J. M. Walenga, Can we improve on the rapid assessment of clinically relevant levels of direct acting oral anticoagulants (DOAC)? Clin. Appl. Thromb. Hemos. 28 (2022) 1–2; https://doi.org/10.1177/10760296221096422 Search in Google Scholar

43. A. Gómez-Outes, P. Alcubilla, G. Calvo-Rojas, A. I. Terleira-Fernández, M. L. Suárez-Gea, R. Lecumberri and E. Vargas-Castrillón, Meta-analysis of reversal agents for severe bleeding associated with direct oral anticoagulants, J. Am. Coll. Cardiol. 77(24) (2021) 2987–3001; https://doi.org/10.1016/j.jacc.2021.04.061 Search in Google Scholar

44. Praxbind (idarucizumab), updated July 27, 2021; https://www.ema.europa.eu/en/documents/overview/praxbind-epar-summary-public_en.pdf; last access date July 05, 2022 Search in Google Scholar

45. R. Bonar, E. J. Favaloro, S. Mohammed, L. Pasalic, J. Sioufi and K. Marsden, The effect of dabigatran on haemostasis tests: a comprehensive assessment using in-vitro and ex-vivo samples, Pathology 47(4) (2015) 355–364; https://doi.org/10.1097/PAT.0000000000000252 Search in Google Scholar

46. J. Douxfils, W. Ageno, C. M. Samama, S. Lessire, H. Ten Cate, P. Verhamme, J. M. Dogné and F. Mullier, Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians, J. Thromb. Haemost. 16(2) (2018) 209–219; https://doi.org/10.1111/jth.13912 Search in Google Scholar

47. T. A. Helin, A. Pakkanen, R. Lassila and L. Joutsi-Korhonen, Laboratory assessment of novel oral anticoagulants: method suitability and variability between coagulation laboratories, Clin. Chem. 59 (5) (2013) 807–814; https://doi.org/10.1373/clinchem.2012.198788 Search in Google Scholar

48. A. Tripodi, V. Chantarangkul, C. Guinet and M. M. Samama, The International normalized ratio calibrated for rivaroxaban has the potential to normalize prothrombin time results for rivaroxaban-treated patients: results of an in vitro study, J. Thromb. Haemost. 9(1) (2011) 226–228; https://doi.org/10.1111/j.1538-7836.2010.04106.x Search in Google Scholar

49. B. T. Samuelson, A. Cuker, D. M. Siegal, M. Crowther and D. A. Garcia, Laboratory assessment of the anticoagulant activity of direct oral anticoagulants (DOACs): A systematic review, Chest 151(1) (2017) 127–138; https://doi.org/10.1016/j.chest.2016.08.1462 Search in Google Scholar

50. J. Douxfils, B. Chatelain, C. Chatelain, J. M. Dogne and F. Mullier, Edoxaban: impact on routine and specific coagulation assays. A practical laboratory guide, Thromb. Haemost. 115(2) (2016) 368–381; https://doi.org/10.1160/TH15-05-0415 Search in Google Scholar

51. E. J. Favaloro, L. Pasalic, J. Curnow and G. Lippi, Laboratory monitoring or measurement of direct oral anticoagulants (DOACs): advantages, limitations and future challenges, Curr. Drug Metab. 18(7) (2017) 598–608; https://doi.org/10.2174/1389200218666170417124035 Search in Google Scholar

52. W. E. Dager, R. C. Gosselin, S. Kitchen and D. Dwyre, Dabigatran effects on the international normalized ratio, activated partial thromboplastin time, thrombin time, and fibrinogen: a multi-center, in vitro study, Ann. Pharmacother. 46(12) (2012) 1627–1636; https://doi.org/10.1345/aph.1R179 Search in Google Scholar

53. A. Siegbahn, J. Oldgren, U. Andersson, M. D. Ezekowitz, P. A. Reilly, S. J. Connolly, S. Yusuf, L. Wallentin, J. W. Eikelboom, D-dimer and factor VIIa in atrial fibrillation – prognostic values for cardiovascular events and effects of anticoagulation therapy – Randomized controlled trial – A RE-LY substudy, Thromb. Haemost. 115(5) (2016) 921–930; https://doi.org/10.1160/TH15-07-0529 Search in Google Scholar

54. D. M. Adcock, R. Gosselin, S. Kitchen and D. M. Dwyre, The effect of dabigatran on select specialty coagulation assays, Am. J. Clin. Pathol. 139(1) (2013) 102–109; https://doi.org/10.1309/AJCPY6G6ZITVKPVH Search in Google Scholar

55. R. C. Gosselin, R. P. Grant and D. M. Adcock, Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban and rivaroxaban on coagulation assays, Int. J. Lab. Hematol. 38(5) (2016) 505–513; https://doi.org/10.1111/ijlh.12528 Search in Google Scholar

56. R. Bonar, E. J. Favaloro, S. Mohammed, M. Ahuja, L. Pasalic, J. Sioufi and K. Marsden, The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples, Pathology 48(1) (2016) 60–71; https://doi.org/10.1016/j.pathol.2015.11.025 Search in Google Scholar

57. G. Gessoni, S. Valverde, L. Valle, P. Caruso, F. Gessoni and R. Valle, Effect of dabigatran on prothrombinase-based assay for detecting activated protein C resistance: an ex vivo and in vitro study in normal subjects and factor V Leiden carriers, Blood Transfus. 15(6) (2017) 562–567; https://doi.org/10.2450/2017.0199-16 Search in Google Scholar

58. S. Margetic and D. Carzavec, Diseases of Hemostasis, in Medical Biochemistry and Laboratory Medicine in Clinical Practice (Ed. E. Topic, D. Primorac, S. Janković and M. Stefanovic), 2nd ed., Medicinska naklada, Zagreb 2018, pp. 351–387. Search in Google Scholar

59. J. Pratt and P. Crispin, Screening test for direct oral anticoagulants with the dilute Russell viper venom time, Eur. J. Haematol. 100(6) (2018) 567–574; https://doi.org/10.1111/ejh.13050 Search in Google Scholar

60. A. L. Sennesael, T. Exner, B. Chatelain, S. Lessire, A. S. Larock, C. Vancraeynest, L. Pochet, J. M. Dogné, A. Spinewine, F. Mullier and J. Douxfils, An optimized dRVVT-based assay to estimate the intensity of anticoagulation in patients treated with direct oral anticoagulants, Thromb. Res. 157 (2017) 29–37; https://doi.org/10.1016/j.thromres.2017.06.034 Search in Google Scholar

61. J. Favresse, B. Lardinois, L. Sabor, B. Devalet, J. Vandepapeliere, M. Braibant, S. Lessire, B. Chat-elain, H. Jacqmin, J. Douxfils and F. Mullier, Evaluation of the DOAC-Stop procedure to overcome the effect of DOACs on several thrombophilia screening tests, TH Open 2(2) (2018) e202-e209; https://doi.org/10.1055/s-0038-1657785 Search in Google Scholar

62. S. Platton and C. Hunt, Influence of DOAC Stop on coagulation assays in samples from patients on rivaroxaban or apixaban, Int. J. Lab. Hematol. 41(2) (2018) 227–233; https://doi.org/10.1111/ijlh.12950 Search in Google Scholar

63. T. Exner, N. Michalopoulos, J. Pearce, R. Xavier and M. T. Ahuja, Simple method for removing DOACs from plasma samples, Thromb. Res. 163 (2018) 117–122; https://doi.org/10.1016/j.thromres.2018.01.047 Search in Google Scholar

64. I. H. Jaffer, N. Chan, R. Roberts, J. C. Fredenburgh, J. W. Eikelboom and J. I. Weitz, Comparison of the ecarin chromogenic assay and diluted thrombin time for quantification of dabigatran concentrations, J. Thromb. Haemost. 15(12) (2017) 2377–2387; https://doi.org/10.1111/jth.13857 Search in Google Scholar

65. S. T. Avecilla, C. Ferell, W. L. Chandler and M. Reyes, Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy, Am. J. Clin. Pathol. 137(4) (2012) 572–574; https://doi.org/10.1309/AJCPAU7OQM0SRPZQ Search in Google Scholar

66. R. C. Gosselin, R. P. Grant and D. M. Adcock, Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban and rivaroxaban on coagulation assays, Int. J. Lab. Hematol. 38(5) (2016) 505–513; https://doi.org/10.1111/ijlh.12528 Search in Google Scholar

67. W. Clarke, J. M. Rhea and R. Molinaro, Challenges in implementing clinical liquid chromatography-tandem mass spectrometry methods–the light at the end of the tunnel, J. Mass Spectrom. 48(7) (2013) 755–767; https://doi.org/10.1002/jms.3214 Search in Google Scholar

68. L. Brunetti, B. Sanchez-Catanese, L. Kagan, X. Wen, M. Liu, B. Buckley, J. P. Luyendyk and M. L. Aleksunes, Evaluation of the chromogenic anti-factor IIa assay to assess dabigatran exposure in geriatric patients with atrial fibrillation in an outpatient setting, Thromb. J. 14 (2016) Article ID 10 (8 pages); https://doi.org/10.1186/s12959-016-0084-2 Search in Google Scholar

69. M. Ebner, I. Birschmann, A. Peter, I. Birschmann, A. Peter, F. Härtig, C. Spencer, J. Kuhn, A. Rupp, G. Blumenstock, C. S. Zuern, U. Ziemann and S. Poli, Limitations of specific coagulation tests for direct oral anticoagulants: A critical analysis, J. Am. Heart Assoc. 7(19) (2018) e009807; https://doi.org/10.1161/JAHA.118.009807 Search in Google Scholar

70. J. Douxfils, A. Tamigniau, B. Chatelain, C. Chatelain, P. Wallemacq, J. M. Dogné and F. Mullie, 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. 110(4) (2013) 723–731; https://doi.org/10.1160/TH13-04-0274 Search in Google Scholar

71. S. Margetić, I. Ćelap, D. Delić Brkljačić, N. Pavlović, S. Šupraha Goreta, I. Kobasić, A. Lovrenčić-Huzjan and V. Bašić Kes, Chromogenic anti-FXa assay calibrated with low molecular weight heparin in patients treated with rivaroxaban and apixaban: possibilities and limitations, Biochem. Med. (Zagreb) 30(1) (2020) Article ID 010702; https://doi.org/10.11613/BM.2020.010702 Search in Google Scholar

72. L. Brückner, J. BeyerWestendorf, O. Tiebel J. Pietsch, Development and validation of an analytical method for the determination of direct oral anticoagulants (DOAC) and the direct thrombininhibitor argatroban by HPLC–MS/MS, J. Thromb. Thrombolysis 53 (2022) 777–787; https://doi.org/10.1007/s11239-021-02596-z Search in Google Scholar

73. R. Aakerøy, C. Stokes, M. Tomić, S. Hegstad, A. H. Kristoffersen, H. Ellekjær, J. Schjøtt, O. Spigset and A. Helland, Serum or plasma for quantification of direct oral anticoagulants?, Ther. Drug Monit. 44(4) (2022) 578–584; https://doi.org/10.1097/FTD.0000000000000956 Search in Google Scholar

74. L. Örd, T. Marandi, M. Märk, L. Raidjuk, J. Kostjuk, V. Banys, K. Krause and M. Pikta, Evaluation of DOAC dipstick test for detecting direct oral anticoagulants in urine compared with a clinically relevant plasma threshold concentration, Clin. Appl. Thromb./Hemost. 28 (2022) 1–8; https://doi.org/10.1177/10760296221084307 Search in Google Scholar

75. J. Harenberg, S. Kraemer, S. Du, C. Giese, A. Schulze, R. Kraemer and C. Weiss, Determination of direct oral anticoagulants from human serum samples, Semin. Thromb. Hemost. 40(1) (2014) 129–134; https://doi.org/10.1055/s-0033-1363462 Search in Google Scholar

76. J. Harenberg, R. Schreiner, S. Hetjens and C. Weiss, Detecting anti-IIa and anti-Xa direct oral anticoagulants (DOAC) agents in urine using a DOAC dipstick, Semin. Thromb. Hemost. 45(3) (2019) 275–284; https://doi.org/10.1055/s-0038-1668098 Search in Google Scholar

77. S. Margetić, I. Ćelap, A. Lovrenčić Huzjan, M. Bosnar Puretić, S. Šupraha Goreta, A. Čajević Glojnarić, D. Delić Brkljačić, P. Mioč, J. Harenberg, S. Hetjens and C. Weiss, DOAC dipstick testing can reliably exclude the presence of clinically relevant DOAC concentrations in circulation, Thromb. Haemost. (2022) ahead of print; https://doi.org/10.1055/a-1753-27 Search in Google Scholar

78. J. Harenberg, S. Du, C. Weiss, R. Kramer, D. Hoppensteadt and J. Walenga, 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. 12(5) (2014) 801–804; https://doi.org/10.1111/jth.12547 Search in Google Scholar

79. S. Du, C. Weiss, G. Christina, S. Krämer, M. Wehling, R. Krämer and J. Harenberg, Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods, Clin. Chem. Lab. Med. 53(8) (2015) 1237–1247; https://doi.org/10.1515/cclm-2014-0991 Search in Google Scholar

80. O. Volod, C. M. Bunch, N. Zackariya, E. E. Moore, H. B. Moore, H. C. Kwaan, M. D. Neal, M. D. Al-Fadhl, S. S.Patel, G. Wiarda, H. D. Al-Fadhl, M. L. McCoy, A. V. Thomas, S. G. Thomas, L. Gillespie, R. Z. Khan, M. Zamlut, P. Kamphues, D. Fries and M. M. Walsh, Viscoelastic hemostatic assays: A primer on legacy and new generation devices, J. Clin. Med. (2022) 11(3) Article ID 860 (22 pages); https://doi.org/10.3390/jcm11030860 Search in Google Scholar

81. D. Oberladstätter, W. Voelckel, C. Schlimp, J. Zipperle, B. Ziegler, O. Grottke, H. Schöchl, A prospective observational study of the rapid detection of clinically-relevant plasma direct oral anticoagulant levels following acute traumatic injury, Anaesthesia 76(3) (2021) 373–380; https://doi.org/10.1111/anae.15254 Search in Google Scholar

82. A. Sedghi, L. Heubner, A. Klimova, O. Tiebel, J. Pietsch, M. Mirus, K. Barlinn, T. T. Talita, T. Minx, J. Beyer-Westendorf, V. Puetz, P. Spieth and Siepmann, Point of care assessment of direct oral anticoagulation in acute ischemic stroke: protocol for a prospective observational diagnostic accuracy study, Thromb. Haemost. (2022) ahead of print; https://doi.org/10.1055/a-1869-785 Search in Google Scholar

83. R. McGrail, J. Revsholm, P. H. Nissen, E. L. Grove and A. M. Hvas, Stability of direct oral anticoagulants in whole blood and plasma from patients in steady state treatment, Thromb. Res. 148 (2016) 107–110; https://doi.org/10.1016/j.thromres.2016.10.023 Search in Google Scholar

84. H. Ten Cate, R. H. Olie, A. J. Ten Cate-Hoek and Y. M. C. Henskens, Direct oral anticoagulants: When to consider laboratory testing?, Int. J. Lab. Hematol. 40(1) (2018) 30–33; https://doi.org/10.1111/ijlh.12816 Search in Google Scholar

85. J. Harenberg, S. Krämer, S. Du, S. Zolfaghari, A. Schulze, R. Krämer, C. Weiss, M. Wehling and G. Y. H. Lip, Measurement of rivaroxaban and apixaban in serum samples of patients, Eur. J. Clin. Invest. 44(8) (2014) 743–752. Search in Google Scholar

86. T. Gous, L. Couchman, J. P. Patel, C. Paradzai, R. Arya and R. J. Flanagan. 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. 36(5) (2014) 597–605. Search in Google Scholar

87. S. Lessire, J. Douxfils, J. Baudar, N. Bailly, A. Dincq, M. Gourdin, J. Dogné, B. Châtelain and F. Mullier, Is thrombin time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study, Thromb. Res. 136(3) (2015) 693–696; https://doi.org/10.1016/j.thromres.2015.07.018 Search in Google Scholar