The effect of warfarin, heparin, and modern directly acting oral anticoagulants (dabigatran etexilate, rivaroxaban, apixaban) on the level of coagulation factors: V, VII, VIII, IX, XII, WF

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Heparin is common initial therapy administered to subjects with acute venous thromboembolism. Routine clinical practice in this case consists of immediate heparin therapy initiation and administration of warfarin sodium within 24 hours; administration of heparin is usually finished in 5 days. Patients with CF-LVAD (continuous flow left ventricular assist device) are also administered intravenous unfractionated heparin. Heparin mainly serves as anticoagulant via catalyzing antithrombin, which leads to factor II (thrombin), factor X inhibition, with smaller effect on IX, XI, XII.

During the last 50 years warfarin has been the most common anticoagulant from vitamin K antagonists group which is used to treat patients with high risk of developing arterial and venous thrombosis. It has narrow therapeutic window due to unfavorable pharmacokinetics, thus requiring frequent monitoring, and it’s affected by interaction with concomitant medications and foods. Apart from this, effect of warfarin is not limited to the influence on hemostasis; it also has impact on all vitamin K-related proteins. Warfarin shows its anticoagulant effect through decreasing functional levels of vitamin K-related factors II, VII, IX and X. Synthesis of two physiologic anticoagulants — C and S proteins — is blocked at the same time. Warfarin competes with vitamin K, thus blocking vitamin K effects.

Modern directly acting oral anticoagulants: direct thrombin inhibitor dabigatran and Xa factor inhibitors — rivaroxaban and apixaban, were developed as an alternative to warfarin. They also show non-hemostatic vascular effects via protease activated receptors (PARs).

作者简介

Darya Gulyaikhina

North-Western State Medical University named after I.I. Mechnikov

编辑信件的主要联系方式.
Email: gde81@mail.ru
ORCID iD: 0000-0002-5208-669X

Assistant of the Department of Transfusiology

俄罗斯联邦, 191015, Saint Petersburg, Kirochnaya street Nr 41.

参考

  1. Hull RD, Raskob GE, Rosenbloom D, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med. 1990;3221260-1264. https://doi.org/10.1056/NEJM199005033221802.
  2. Adatya S, Sunny R, Fitzpatrick MJ, et al. Coagulation factor abnormalities related to discordance between anti-factor Xa and activatedpartial thromboplastin time in patients supported with continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2016;35(11):1311-1320. https://doi.org/10.1016/j.healun.2016.09.010.
  3. van Gorp RH, Schurgers LJ. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) VersusDirect Oral Anticoagulants (DOACs). Nutrients. 2015;7(11):9538-57. https://doi.org/10.3390/nu7115479.
  4. Wojciechowski VV, Calina D, Tsarouhas K, et al. A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian perspective. Daru. 2017;25(1):10. https://doi.org/10.1186/s40199-017-0175-z.
  5. Sardar P, Chatterjee S, Wu WC, et al. New oral anticoagulants are not superior to warfarin in secondary prevention of stroke or transient ischemic attacks, but lower the risk of intracranial bleeding: insights from a meta-analysis and indirect treatment comparisons. PLoS One.2013;8(10):e77694. https://doi.org/10.1371/journal.pone.0077694.
  6. van Gorp RH, Schurgers LJ. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) VersusDirect Oral Anticoagulants (DOACs). Nutrients. 2015;7(11):9538-57. https://doi.org/10.3390/nu7115479.
  7. Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost. 1999;82:165-174. https://doi.org/10.1055/s-0037-1615780.
  8. Macfarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature. 1964;202:498-499. https://doi.org/10.1038/202498a0.
  9. Colman RW. Are hemostasis and thrombosis two sides of the same coin? J Exp Med. 2006;203:493-495. https://doi.org/10.1084/jem.20060217.
  10. Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet. 1999;353:1167-1173. https://doi.org/10.1016/s0140-6736(98)10266-0.
  11. Saffian SM, Duffull SB, Roberts RL, et al. Influence of Genotype on Warfarin Maintenance Dose Predictions Produced Using a Bayesian Dose Individualization Tool. Ther Drug Monit. 2016;38:677-83. https://doi.org/10.1097/ftd.0000000000000347.
  12. Ageno W, Gallus AS, Wittkowsky A, et al.; American College of Chest P. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis. 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e44S-88S. https://doi.org/10.1378/chest.11-2292.
  13. Holbrook A, Schulman S, Witt DM, et al.; American College of Chest P. Evidence based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis. 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest.2012;141:e152S-84S. https://doi.org/10.1378/chest.11-2295.
  14. Makris M, Watson HG. The management of coumarin-induced overanticoagulation Annotation. Br J Haematol. 2001;114:271-80. https://doi.org/10.1046/j.1365-2141.2001.02908.x.
  15. Wojciechowski VV, Calina D, Tsarouhas K, et al. A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian perspective. DARU Journal of Pharmaceutical Sciences. 2017;25:10. https://doi.org/10.1186/s40199-017-0175-z.
  16. Wojciechowski et al. DARU Journal of Pharmaceutical Sciences (2017) 25:10 Page 9 of 10. https://doi.org/10.1002/ajh.20784.
  17. Kruse JA, Carlson RW. Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med. 1992;21:331-6. https://doi.org/10.1016/s0196-0644(05)80900-x.
  18. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002-12. https://doi.org/10.1056/nejmsa1103053.
  19. Lubetsky A, Yonath H, Olchovsky D, et al. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med. 2003;163:2469-73. https://doi.org/10.1016/j.accreview.2003.12.021.
  20. Makris M, Van Veen JJ. Three- or four-factor prothrombin complex concentrate for emergency anticoagulation reversal? Blood Transfus. 2011;9:117-9. https://doi.org/10.2450/2011.0017-11.
  21. O’Shaughnessy DF, Atterbury C, Bolton Maggs P, et al.; British Committee for Standards in Haematology BTTF. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004;126:11-28. https://doi.org/10.1111/j.1365-2141.2004.04972.x.
  22. Hylek EM, Held C, Alexander JH, Lopes RD, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol. 2014;63(20):2141-2147. https://doi.org/10.1016/j.jacc.2014.02.549.
  23. Majeed A, Hwang H-G, Brueckmann M, et al. Management and outcomes of major bleeding on dabigatran or warfarin. Blood. 2013;128(21):2325-2332. https://doi.org/10.1161/CIRCULATIONAHA.114.010280.
  24. Beyer-Westendorf J, Ebertz F, Förster K, et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost. 2015;113(6):1247-1257. https://doi.org/10.1160/TH14-11-0954.
  25. Beyer-Westendorf J, Förster K, Pannach S, et al. Rates, management and outcome of bleeding complications during rivaroxaban therapy in daily care: results from the Dresden NOAC registry. Blood. 2014;124(6):955-962. https://doi.org/10.1182/blood-2014-03-563577.
  26. Xu Y, Schulman S, Dowlatshahi D, et al.; Bleeding Effected by Direct Oral Anticoagulants (BLED-AC) Study Group. Direct Oral Anticoagulant- or Warfarin Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study. Chest.2017;152(1):81-91. https://doi.org/10.1016/j.chest.2017.02.009.
  27. Diener HC, Connolly SJ, Ezekowitz MD, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010;9:1157-1163. https://doi.org/10.1016/S1474-4422(10)70274-X.
  28. Hankey GJ, Patel MR, Stevens SR, et al. ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11:315-322. https://doi.org/10.1016/S1474-4422(12)70042-X.
  29. Easton JD, Lopes RD, Bahit MC, et al. ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11:503-511. https://doi.org/10.1016/S1474-4422(12)70092-3.
  30. Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-694. https://doi.org/10.1111/j.1538-7836.2005.01204.x.
  31. Gomes T, Mamdani MM, Holbrook AM, et al. Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ. 2013;185(2):E121-E127. https://doi.org/10.1503/cmaj.121218.
  32. Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32:546-58. https://doi.org/10.1002/j.1875-9114.2011.01049.x.
  33. Price EA, Jin J, Nguyen HM, et al. Discordant aPTT and anti-Xa values and outcomes in hospitalized patients treated with intravenous unfractionated heparin. The Annals of Pharmacotherapy. 2013;47:151-8. https://doi.org/10.1345/aph.1R635.
  34. Kearon C, Johnston M, Moffat K, et al. Effect of warfarin on activated partial thromboplastin time in patients receiving heparin. Arch Intern Med. 1998;158(10):1140-3. https://doi.org/10.1001/archinte.158.10.1140.
  35. Douxfils J, Mullier F, Loosen C, et al. Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendationsfor the monitoring of rivaroxaban and review of the literature. Thromb Res. 2012;130(6):956-66. https://doi.org/10.1016/j.thromres.2012.09.004.
  36. Barrett YC, 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;104:1263-71. https://doi.org/10.1160/TH10-05-0328.
  37. Hillarp A, Baghaei F, Blixter IF, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost. 2010;9:133-9. https://doi.org/10.1111/j.1538-7836.2010.04098.x.
  38. Samama MM, Martinoli JL, LeFlem L, et al. Assessment of laboratory assays to measure rivaroxaban — an oral, direct factor Xa inhibitor. Thromb Haemost. 2010;103:815-25. https://doi.org/10.1160/TH09-03-0176.
  39. Mani H, Hesse C, Stratmann G, Lindhoff-Last E. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factoractivities in patients under real life conditions. Thromb Haemost. 2013;109(1):127-36. https://doi.org/10.1160/TH12-04-0228.
  40. Harenberg J, Marx S, Kramer R, et al. Determination of an international sensitivity index of thromboplastin reagents using a WHO thromboplastin as calibrator for plasma spiked with rivaroxaban. Blood Coagul Fibrinolysis. 2011;22:637-41. https://doi.org/10.1097/MBC.0b013e328349f1d6.
  41. Asmis LM, Alberio L, Angelillo-Scherrer A, et al. Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests A study in 9 Swiss laboratories. Thromb Res. 2012;129:492-8. https://doi.org/10.1016/j.thromres.2011.06.031.
  42. Lindhoff-Last E, Samama MM, Ortel TL, et al. Assays for measuring rivaroxaban: their suitability and limitations. Ther Drug Monit. 2010;32:673-9. https://doi.org/10.1097/FTD.0b013e3181f2f264.
  43. Uriel N, Pak SW, Jorde UP, et al. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol. 2010;56:1207-13. https://doi.org/10.1016/j.jacc.2010.05.016.
  44. Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant. 2013;32:157-87. https://doi.org/10.1016/j.healun.2012.09.013.
  45. Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to longterm warfarin therapy. J Heart Lung Transplant. 2010;29:616-24. https://doi.org/10.1016/j.healun.2010.02.003.
  46. Schulman S, Kearon C, Kakkar AK, et al.; RE-COVER Study Group Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-2352. https://doi.org/10.1056/NEJMoa0906598.
  47. Ferreira J, Ezekowitz MD, Connolly SJ, et al.; RE-LY Investigators. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heartfailure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail. 2013;15(9):1053-61. https://doi.org/10.1093/eurjhf/hft111.
  48. Bounameaux H, Reber G. New oral antithrombotics: a need for laboratory monitoring. Against J Thromb Haemost. 2010;8:627-30. https://doi.org/10.1111/j.1538-7836.2010.03759.x.
  49. Ten Cate H. Monitoring new oral anticoagulants, managing thrombosis, or both? Thromb Haemost. 2012;107. https://doi.org/10.1160/TH12-03-0130.
  50. Kubitza D, Becka M, Mueck W, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2010;70:703-12. https://doi.org/10.1111/j.1365-2125.2010.03753.x.
  51. Lassen MR, Gallus A, Raskob GE, et al. ADVANCE-3 Investigators Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363:2487-2498. https://doi.org/10.1056/NEJMoa1006885.
  52. Van Es N, Coppens M, Schulman S, et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: Evidence from phase 3 trials. Blood. 2014;124:1968-1975. https://doi.org/10.1182/blood-2014-04-571232.
  53. Burns ER, Goldberg SN, Wenz B. Paradoxic effect of multiple mild coagulation factor deficiencies on the prothrombin time and activated partial thromboplastin time. Am J Clin Pathol. 1993;100:94-8. https://doi.org/10.1093/ajcp/100.2.94.
  54. Dobran M, Iacoangeli M, Scortichini AR, et al. Spontaneous chronic subdural hematoma in young adult: the role of missing coagulation factors. G Chir. 2017;38(2):66-70. https://doi.org/10.11138/gchir/2017.38.2.066.
  55. Echahdi H, El Hasbaoui B, El Khorassani M, et al. Von Willebrand’s disease: case report and review of literature. Pan Afr Med J. 2017;27:147. https://doi.org/10.11604/pamj.2017.27.147.12248.
  56. Renne T, Schmaier AH, Nickel KF, et al. In vivo roles of factor XII. Blood. 2012;120:4296-303. https://doi.org/10.1182/blood-2012-07-292094.
  57. Cohen D. Dabigatran: How the drug company withheld important analyses. BMJ. 2014;349. https://doi.org/10.1136/bmj.g4670.
  58. Lippi G, Favaloro EJ, Mattiuzzi C. Combined administration of antibiotics and direct oral anticoagulants: A renewed indication for laboratory monitoring? Semin Thromb Hemost. 2014;40:756-765. https://doi.org/10.1055/s-0034-1381233.
  59. Crowther M, Crowther MA. Antidotes for Novel Oral Anticoagulants: Current Status and Future Potential. Arterioscler. Thromb Vasc Biol. 2015;35:1736-1745. https://doi.org/10.1161/ATVBAHA.114.303402.
  60. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373:511-520. https://doi.org/10.1056/NEJMoa1502000.

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