Bleeding in patients on direct oral anticoagulants therapy: diagnostic-therapeutic management
Authors:
Tomáš Bolek; Matej Samoš; Jakub Benko; Jakub Jurica; Martin Jozef Péč; Marek Cingel; Marián Mokáň
Authors‘ workplace:
I. interná klinika JLF UK a UNM, Martin
Published in:
Forum Diab 2022; 11(2): 108-112
Category:
Overview
Direct oral anticoagulants (DOAC) offer predictable and efficient anticoagulation, oral rout of administrative, with fix dosing, no need for routine laboratory monitoring and good safety profile. European Society of Cardiology (ESC) recommends DOAC therapy rather than vitamin K antagonist therapy in patients with non-valvular atrial fibrillation. DOAC are becoming drugs of choice in routine clinical practice. As number of DOAC-treated patients rises, there is an increase in DOAC therapy-related bleeding. In this review article we summarize currently available diagnostic and therapeutic approaches in patients with bleeding while on DOAC.
Keywords:
direct oral anticoagulants (DOAC) – bleeding – atrial fibrillation
Sources
1. Chaudhary R, Sharma T, Garg J et al Direct oral anticoagulants: a review on the current role and scope of reversal agents. J Thromb Thrombolysis 2020; 49(2): 271–286. Dostupné z DOI: <http://dx.doi.org/10.1007/s11239–019–01954–2>.
2. Conolly SJ, Ezekowitz M, Yusuf S et al. [RE-LY Steering Committee and Investigators]. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361(12): 1139 -1151. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0905561>.
3. Patel MR, Mahaffey KW, Garg J et al. [ROCKET AF Investigators]. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365(10): 883–891. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1009638>.
4. Granger CB, Alexander JH, McMurray JJ et al. [ARISTOTLE Committees and Investigators]. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365(11): 981–992. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1107039>.
5. Giugliano RP, Ruff CT, 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. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1310907>.
6. 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(24): 2342–2352. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0906598>.
7. Bauersachs R, Berkowitz SD, Brenner B et al. [EINSTEIN Investigators]. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363(26): 2499–2510. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1007903>.
8. Büller HR, Prins MH, Lensin AW et al. [EINSTEIN–PE Investigators]. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N EnglJ Med 2012; 366(14): 1287–1297. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1113572>.
9. Agnelli G, Buller HR, Cohen A et al. [AMPLIFY Investigators]. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369(9): 799–808. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1302507>.
10. Büller HR, Décousus H, Grosso MA et al. [Hokusai-VTE Investigators]. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369(15): 1406–1415. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1306638>.
11. Samos M, Stanciakova L, Skornova I et al. Review of the Pharmacology of the Emerging Possibilities of the Direct Oral Anticoagulants' Reversal. Curr Drug Metab 2017; 18(7): 643–650. Dostupné z DOI: <http://dx.doi.org/10.2174/1389200218666170413155351>.
12. Steffel J, Collins R, Antz M et al. [External reviewers]. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace 2021; 23(10): 1612–1676. Dostupné z DOI: <http://dx.doi.org/10.1093/europace/euab065>.
13. Schattner A, Kozak N, Friedman J. Case report: fatality in a patient treated with dabigatran. Am J Emerg Med 2013; 31: 443.e1–443.e2. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ajem.2012.05.022>.
14. Simonsen CZ, Steiner T, Tietze A et al. Dabigatran-related intracerebral hemorrhage resulting in hematoma expansion. J Stroke Cerebrovasc Dis 2014; 23(2): e133-e134. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.08.011>.
15. Warkentin TE, Margetts P, Connolly SJ et al. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran associated postcardiac surgery bleeding. Blood 2012; 119(9): 2172–2174. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2011–11–393587>.
16. Cano EL, Miyares MA. Clinical challenges in a patient with dabigatran-induced fatal hemorrhage. J Geriatr Pharmacother 2012; 10(2): 160–163. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjopharm.2012.02.004>.
17. Dy EA, Shiltz DL. Hemopericardium and cardiac tamponade associated with dabigatran use. Ann Pharmacother 2012; 46(7–8): e18. Dostupné z DOI: <http://dx.doi.org/10.1345/aph.1R112>.
18. Legrand M, Mateo J, Aribaud A et al. The use of dabigatran in elderly patients. Arch Intern Med 2011; 171(14): 1285–1288. Dostupné z DOI: <http://dx.doi.org/10.1001/archinternmed.2011.314>.
19. Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct thrombin inhibitors – catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. J Neurosurg 2012; 116(5): 1093–1096. Dostupné z DOI: <http://dx.doi.org/10.3171/2012.2.JNS112132>.
20. Ross B, Miller MA, Ditch K, Tran M. Clinical experience of life-threatening dabigatran-related bleeding at a large, tertiary care, academic medical center: a case series. J Med Toxicol 2014; 10(2): 223–228. Dostupné z DOI: <http://dx.doi.org/10.1007/s13181–013–0364–1>.
21. Jaeger M, Jeanneret B, Schaeren S. Spontaneous spinal epidural haematoma during Factor Xa inhibitor treatment (Rivaroxaban). Eur Spine J 2012; 21(Suppl 4): S433-S435. Dostupné z DOI: <http://dx.doi.org/10.1007/s00586–011–2003–3>.
22. Boland M, Murphy M, Murphy M et al. Acute-onset severe gastrointestinal tract hemorrhage in a postoperative patient taking rivaroxaban after total hip arthroplasty: a case report. J Med Case Rep 2012; 6: 129. Dostupné z DOI: <http://dx.doi.org/10.1186/1752–1947–6-129>.
23. Lo JC, Gerona RR. A case of rivaroxaban associated intracranial hemorrhage. West J Emerg Med 2014; 15(4): 375–377. Dostupné z DOI: <http://dx.doi.org/10.5811/westjem.2014.2.19440>.
24. Calıskan F, Akdemir HU, Nurata H et al. Rıvaroxaban-induced severe diffuse ıntracerebral hemorrhage. Am J Emerg Med 2015; 33(3): 475. e1-e5. Dostupné z DOI: Dostupné z DOI: <http://dx.doi.org/10.1016/j.ajem.2014.08.028>.
25. Shivamurthy P, Brar N, Therrien ML. Isolated hemopericardium associated with rivaroxaban: first case report. Pharmacotherapy 2014; 34(9): e169-e172. <http://dx.doi.org/10.1002/phar.1474>.
26. Rinehart DR, Lockhart NR, Hamilton LA et al. Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity. Crit Care Med 2015; 43(6): e203-e207. Dostupné z DOI: <http://dx.doi.org/10.1097/CCM.0000000000000909>.
27. Beynon C, Potzy A, Unterberg AW et al. Emergency neurosurgical care in patients treated with apixaban: report of 2 cases. Am J Emerg Med 2015; 33(6): 858.e5-e7. <http://dx.doi.org/10.1016/j.ajem.2014.12.017>.
28. Bouget J, Oger E. Emergency admissions for major haemorrhage associated with direct oral anticoagulants. Thromb Res 2015; 136(6): 1190–1194. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2015.10.036>.
29. Ray WA, Chung CP, Murray KT et al. Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy with Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA 2018; 320(21): 2221–2230. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2018.17242>.
30. Tomaselli GF, Mahaffey KF, Cuker A et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020; 76(5): 594–622. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2020.04.053>.
31. Fakhry SM, Fata P. How low is too low? Cardiac risks with anemia. Crit Care 2004; 8(Suppl 2): S11-S14. Dostupné z DOI: <http://dx.doi.org/10.1186/cc2845>.
32. Cuker A, Siegal D. Monitoring and reversal of direct oral anticoagulants. Hematology Am Soc Hematol Educ Program 2015; 2015: 117–124. Dostupné z DOI: <http://dx.doi.org/10.1182/asheducation-2015.1.117>.
33. Samuelson BT, Cuker A, Siegal DM et al. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: a systematic review. Chest 2017; 151(1): 127–138. Dostupné z DOI: <http://dx.doi.org/10.1016/j.chest.2016.08.1462>.
34. Cuker A. Laboratory measurement of the non-vitamin K antagonist oral anticoagulants: selecting the optimal assay based on drug, assay availability, and clinical indication. J Thromb Thrombolysis 2016; 41(2): 241–247. Dostupné z DOI: <http://dx.doi.org/10.1007/s11239–015–1282–7>.
35. Heidbuchel H, Verhamme P, Alings M et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2017; 38(27): 2137–2149. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw058>.
36. Batchelor JS, Grayson A. A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage. BMJ Open 2012; 2(2): e000588. Dostupné z DOI: <http://dx.doi.org/10.1136/bmjopen-2011–000588>.
37. Pollack CV, Reilly PA, Bernstein R et al. Design and rationale for REVERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost 2015; 114(1): 198–205. Dostupné z DOI: <http://dx.doi.org/10.1160/TH15–03–0192>.
38. Wong H, Keeling D. Activated prothrombin complex concentrate for the prevention of dabigatran-associated bleeding. Br J Haematol 2014; 166(1): 152–153. Dostupné z DOI: <http://dx.doi.org/10.1111/bjh.12831>.
39. Connolly SJ, Crowther M, Eikelboom JW et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med 2019; 380(14): 1326–1335. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1814051>.
40. Crowther M, Lu G, Leeds J et al. A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of edoxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), a universal antidote for factor Xa (fXa) inhibitors. Blood 2014; 124(21): 4269. Dostupné z DOI: <https://doi.org/10.1182/blood.V124.21.4269.4269>.
41. Majeed A, Agren A, Holmstrom M et al. Management of rivaroxabanor apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 2017; 130(15): 1706–1712. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2017–05–782060>.
42. Piran S, Khatib R, Schulman S et al. Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis. Blood Adv 2019; 3(2): 158–167. Dostupné z DOI: <http://dx.doi.org/10.1182/bloodadvances.2018024133>.
43. 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. Dostupné z DOI: <http://dx.doi.org/10.1160/TH09–11–0758>.
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Forum Diabetologicum
2022 Issue 2
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