Статья
Современные возможности использования лабораторных методов контроля эффективности и безопасности применения прямых пероральных антикоагулянтов
Рассмотрены современные подходы к использованию лабораторных методов для усовершенствования тактики применения прямых пероральных антикоагулянтов (ПОАК). Приводятся клинические ситуации, при которых может быть обоснованным использование данных о концентрации ПОАК в крови, включая очень пожилой возраст, выраженное отклонение от нормы массы тела или нарушение функции почек. Рассматриваются данные о роли измерения уровня ПОАК в крови в случае развития заболеваний или осложнений, при которых требуется получение информации о сохранении антикоагулянтного действия ПОАК, например, при развитии тяжелого кровотечения или необходимости выполнения неотложного хирургического вмешательства. Обсуждаются преимущества и ограничения современных лабораторных методов оценки концентрации ПОАК в крови. Подчеркивается, что к одному из основных преимуществ применения ПОАК относится отсутствие необходимости контроля за лабораторными показателями у большинства пациентов. Приводятся данные фармакологических исследований, которые могут быть полезны в объяснении механизмов, определяющих более высокую безопасность одних ПОАК по сравнению с другими. Обсуждаются перспективные методы оценки уровня ПОАК в крови, а также возможность использования менее специфичных реактивов для оценки концентрации ПОАК. Рассматривается возможность использования менее специфичных, но более доступных методов оценки концентрации ингибиторов Ха фактора в крови, в частности реактива для оценки уровня антифактора, который применяется для определения уровня гепарина в крови. Приводятся мнения экспертов о роли оценки уровня ПОАК в крови и возможности тактики подбора доз ПОАК на основании данных лабораторных анализов.
1. Chan N, Sager PT, Lawrence J, et al. Is there a role for pharmacokinetic/ phar macodynamic-guided dosing for novel oral anticoagulants? Am Heart J. 2018;199:59-67. DOI:10.1016/j.ahj.2017.10.002.
2. Chan NC, Eikelboom JW, Weitz JI. Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants. Circ Res. 2016;118(9):14091424. DOI:10.1161/CIRCRESAHA.116.306925.
3. Lee JJ, Ha ACT, Dorian P, Verma M, et al. Meta-Analysis of Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin According to Time in Therapeutic Range in Atrial Fibrillation. Am J Cardiol. 2021;140:62-68. DOI:10.1016/j.amjcard.2020.10.064.
4. Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2018;118(3):437-450. DOI:10.1055/s-0038-1627480.
5. Douxfils J, Ageno W, Samama CM, et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost. 2018;16(02):209-219. DOI:10.1111/jth.13912.
6. Toorop MMA, Lijfering WM, Scheres LJJ. The relationship between DOAC levels and clinical outcomes: The measures tell the tale. J Thromb Haemost. 2020;18(12):3163-3168. DOI:10.1111/jth.15104.
7. Douxfils J, Mullier F, Dogné JM. Dose tailoring of dabigatran etexilate: obvious or excessive? Expert Opin Drug Saf. 2015;14(8):1283-1289. DOI:10.1517/14740338.2015.1049995.
8. Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. J Am Heart Assoc. 2016;5(05):e003432. DOI:10.1161/JAHA.116.003432.
9. Buckley LF, Rybak E, Aldemerdash A, et al. Direct oral anticoagulants in patients with atrial fibrillation and renal impairment, extremes in weight, or advanced age. Clin Cardiol. 2017;40(01):46-52. DOI:10.1002/clc.22591.
10. Chan KE, Giugliano RP, Patel MR, et al. Nonvitamin K anticoagulant agents in patients with advanced chronic kidney disease or on dialysis with AF. J Am Coll Cardiol. 2016;67(24):2888-2899. DOI:10.1016/j.jacc.2016.02.082.
11. Levy JH, Ageno W, Chan NC, et al.; 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(03):623-627. DOI:10.1111/jth.13227.
12. Lindhoff-Last E. Direct oral anticoagulants (DOAC) — Management of emergency situations. Hamostaseologie. 2017;37(4):257-266. DOI:10.5482/HAMO-16-11-0043.
13. Gendron N, Gay J, Lemoine M, et al. Usefulness of initial plasma dabigatran concentration to predict rebound after reversal. Haematologica. 2018; 103(05):e226-e229. DOI:10.3324/haematol.2017.183400.
14. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):13301393. DOI:10.1093/eurheartj/ehy136.
15. Tripodi A. To measure or not to measure direct oral anticoagulants before surgery or invasive procedures: reply. J Thromb Haemost. 2016;14(12):25592561. DOI:10.1111/jth.13513.
16. Tripodi A. To measure or not to measure direct oral anticoagulants before surgery or invasive procedures. J Thromb Haemost. 2016;14(7):1325-1327. DOI:10.1111/jth.13344.
17. Tripodi A, Marongiu F, Moia M, et al. The vexed question of whether or not to measure levels of direct oral anticoagulants before surgery or invasive procedures. Intern Emerg Med. 2018;13(7):1029-1036. DOI:10.1007/s11739-018-1854-6.
18. Albaladejo P, Bonhomme F, Blais N, et al. Management of direct oral anticoagulants in patients undergoing elective surgeries and invasive procedures: Updated guidelines from the French Working Group on Perioperative Hemostasis (GIHP) — September 2015. Anaesth Crit Care Pain Med. 2017;36(1):73-76. DOI:10.1016/j.accpm.2016.09.002.
19. Rimsans J, Douxfils J, Smythe MA, Gosselin RC. Overview and Practical Application of Coagulation Assays in Managing Anticoagulation with Direct Oral Anticoagulants (DOACs). Curr Pharmacol Rep. 2020;6:241-259. DOI:10.1007/s40495-020-00232-7.
20. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019;179(11):1469-1478. DOI:10.1001/jamainternmed.2019.2431.
21. Shaw JR, Li N, Vanassche T, Coppens M, et al. Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. Blood Adv. 2020;4(15):3520-3527. DOI:10.1182/bloodadvances.2020002335.
22. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14(6):1308-1313. DOI:10.1111/jth.13323.
23. Moll S, Crona DJ, Martin K. Direct oral anticoagulants in extremely obese patients: OK to use? Res Pract Thromb Haemost. 2018;3(2):152-155. DOI:10.1002/rth2.12178.
24. Jamieson MJ, Byon W, Dettloff RW, et al. Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data. Am J Cardiovasc Drugs. 2022;22(6):615-631. DOI:10.1007/s40256-022-00524-x.
25. Testa S, Legnani C, Antonucci E, et al. Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2019;17(7):1064-1072. DOI:10.1111/jth.14457.
26. Testa S, Paoletti O, Legnani C, et al. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2018;16(5):842-848. DOI:10.1111/jth.14001.
27. Salmonson T, Dogné JM, Janssen H, et al. Non-vitamin-K oral anticoagulants and laboratory testing: now and in the future: Views from a workshop at the European Medicines Agency (EMA). Eur Heart J Cardiovasc Pharmacother. 2017;3:(1):42-47. DOI:10.1093/ehjcvp/pvw032.
28. Meinel TR, Wilson D, Gensicke H, et al.; DOAC-IVT Writing Group for the International DOAC-IVT, TRISP, and CRCS-K-NIH Collaboration. Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants. JAMA Neurol. 2023;80(3):233-243. DOI:10.1001/jamaneurol.2022.4782. Erratum in: JAMA Neurol. 2023;80(4):422.
29. Willmann S, Thelen K, Kubitza D, et al. Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study. Thromb J. 2018;16:32. DOI:10.1186/s12959-018-0185-1.
30. Rahman M, George C, Monagle P. Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders. Int J Lab Hematol. 2020;42(1):68-74. DOI:10.1111/ijlh.13198.
31. Sarode R. Direct oral anticoagulant monitoring: what laboratory tests are available to guide us? Hematology Am Soc Hematol Educ Program. 2019;2019(1):194–197. DOI:10.1182/hematology.2019000027.
32. Douxfils J, Adcock DM, Bates SM, Favaloro EJ, et al. 2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants. Thromb Haemost. 2021;121(8):1008-1020. DOI:10.1055/a-1450-8178.
33. Tarn D, Shih K, Tseng C, et al. Reasons for Nonadherence to the Direct Oral Anticoagulant Apixaban: A Cross-Sectional Survey of Atrial Fibrillation Patients. JACC Adv. 2023;2(1):100175. DOI:10.1016/j.jacadv.2022.100175.
34. Samoš M, Bolek T, Stančiaková L, et al. Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation? J Clin Med. 2022;11(21):6369. DOI:10.3390/jcm11216369.
35. Reilly PA, Lehr T, Haertter S, et al. 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. DOI:10.1016/j.jacc.2013.07.104.
36. Sakaguchi T, Osanai H, Murase Y, et al. Monitoring of anti-Xa activity and factors related to bleeding events: A study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban. J Cardiol. 2017;70(3):244-249. DOI:10.1016/j.jjcc.2016.11.013.
37. Gao H, Li Y, Sun H, et al. Trough Concentration Deficiency of Rivaroxaban in Patients With Nonvalvular Atrial Fibrillation Leading to Thromboembolism Events. J Cardiovasc Pharmacol. 2022;80(6):869-876. DOI:10.1097/FJC.0000000000001360.
38. Sin CF, Wong KP, Wong HM, et al. Plasma Rivaroxaban Level in Patients With Early Stages of Chronic Kidney Disease-Relationships With Renal Function and Clinical Events. Front Pharmacol. 2022;13:888660. DOI:10.3389/fphar.2022.888660.
39. Škorňová I, Samoš M, Bolek T, et al. Direct Oral Anticoagulants Plasma Levels in Patients with Atrial Fibrillation at the Time of Bleeding: A Pilot Prospective Study. J Cardiovasc Pharmacol. 2021;78(1):e122-e127. DOI:10.1097/FJC.0000000000001038.
40. Nosáľ V, Petrovičová A, Škorňová I, et al. Plasma levels of direct oral anticoagu- lants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study. Eur J Clin Pharmacol. 2022;78(4):557-564. DOI:10.1007/s00228-022-03280-8.
41. Favaloro EJ, Pasalic L, Curnow J, Lippi G. Laboratory Monitoring or Measure - ment of Direct Oral Anticoagulants (DOACs): Advantages, Limitations and Future Challenges. Curr Drug Metab. 2017;18(7):598-608. DOI:10.2174/1389200218666170417124035.
42. Yates SG, Smith S, Tharpe W, et al. Can an anti-Xa assay for low-molecular-weight heparin be used to assess the presence of rivaroxaban? Transfus Apher Sci. 2016;55(2):212-215. DOI:10.1016/j.transci.2016.06.005.
43. Sabor L, Raphaël M, Dogné JM, et al. Heparin-calibrated chromogenic anti-Xa assays are not suitable to assess the presence of significant direct factor Xa inhibitors levels. Thromb Res. 2017;156:36-38. DOI:10.1016/j.thromres.2017.05.024.
44. Margetić S, Ćelap I, Delić Brkljačić D, et al. Chromogenic anti-FXa assay calibrated with low molecular weight heparin in patients treated with rivaroxaban and apixaban: possibilities and limitations. Biochem Med (Zagreb). 2020;30(1):010702. doi: 10.11613/BM.2020.010702.
45. Sairaku A, Nakano Y, Onohara Y, et al. Residual anticoagulation activity in atrial fibrillation patients with temporary interrupted direct oral anticoagulants: Comparisons across 4 drugs. Thromb Res. 2019;183:119-123. DOI:10.1016/j.thromres.2019.10.006.
46. Artang R, Dias JD, Walsh M, et al. Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography. TH Open. 2021;5(4):e570-e576. DOI:10.1055/a-1692-1415.
47. Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016;388(10055):2015-2022. DOI: 10.1016/S01406736(16)31323-X.