Rivaroxaban reversal

From WikEM
Jump to: navigation, search

Background

  • Millions are prescribed rivaroxaban (Xarelto) for atrial fibrillation, cardiac stents, stroke prevention, DVT/PE and ACS prophylaxis
  • Benefits: supposedly easier to dose, less monitoring than older anticoagulants
  • Downside: uncertainty regarding best mechanism of reversal in case of catastrophic intracranial or GI bleed
  • Multiple studies done since introduction of direct thrombin inhibitor (DTI) dabigatran and Factor Xa inhibitors rivaroxaban and apixaban to determine testing for supratherapeutic levels and best means of reversal, however no good trials that assessing human subjects who are potentially supratherapeutic and symptomatic

Clinical Features

  • Patient taking rivaroxaban with a life-threatening bleeding event (GI, ICH, etc.)

Differential Diagnosis

  • Bleeding secondary to other coagulopathy
  • Spontaneous bleeding

Evaluation

  • CBC
  • aPTT/PT: Factor Xa inhibitors affect PT, however unlike with warfarin, degree of PT elevation not directly correlated to level of anticoagulation
  • non contrast head CT showing ICH
  • Antifactor Xa assays- measure drug levels but not degree of anticoagulation, need to be calibrated for rivaroxaban not LMWH, and often not available in a timely fashion
  • Evaluation of clinical manifestation of bleeding (e.g. head CT, endoscopy)

Management

  • IV/O2/Monitor, ABCs
  • Standard resuscitation with IVF; PRBCs if needed
  • If ICH, treat for increased ICP
  • Currently published manuscripts and protocols is that either PCC or aPCC is recommended as a reversal agent for DTIs and FXa inhibitors, with no clear data as to which is superior.
  • Consider Tranexamic acid

Factor Xa Inhibitor Reversal

Anticoagulant Half-life Removed by HD Strategies to reverse or minimize anticoagulant effects
Apixaban (Eliquis®) 8-15 hrs (longer in renal impairment) No
  • If ingested within 2 hours, administer activated charcoal
  • 4-factor PCC (Kcentra™)^
    • 25units/kg—max 2500 units for treatment of documented intracranial hemorrhage
    • 50 units/kg—max 5000 units for all other life-threatening bleeds
Edoxaban (Savaysa®) 10-14 hrs (longer in renal impairment) ~ 25% As above
Rivaroxaban (Xarelto®) 9-13 hrs (longer in renal impairment) No As above
Fondaparinux (Arixtra®) 17-21 hrs (significantly longer in renal impairment) No 4-factor PCC (Kcentra™)^ 50 units/kg—max 5000 units

^Off-label

Disposition

  • admission to a monitored setting

See Also

External Links

References

  1. Akwaa, F., & Spyropoulos, A. (2013). Treatment of Bleeding Complications When Using Oral Anticoagulants for Prevention of Strokes. Current Treatment Options In Cardiovascular Medicine, 15(3), 288-298. doi:10.1007/s11936-013-0238-5
  2. Awad, N., & Cocchio, C. (2013). Activated Prothrombin Complex Concentrates for the Reversal of Anticoagulant-Associated Coagulopathy. Pharmacy And Therapeutics, 38(11), 696.
  3. Babilonia, K., & Trujillo, T. (2014). The role of prothrombin complex concentrates in reversal of target specific anticoagulants. Thrombosis Journal, 12(1), 8. doi:10.1186/1477-9560-12-8
  4. Davis, P., Musunuru, H., Walsh, M., Mitra, R., Ploplis, V., & Castellino, F. (2012). The ex vivo reversibility of dabigatran-induced whole-blood coagulopathy as monitored by thromboelastography: Mechanistic implications for clinical medicine. Thromb Haemost, 108(3), 586-588. doi:10.1160/th12-04-0222
  5. Ebright, J., & Mousa, S. (2014). Oral Anticoagulants and Status of Antidotes for the Reversal of Bleeding Risk. Clinical And Applied Thrombosis/Hemostasis. doi:10.1177/1076029614545211
  6. Eerenberg, E., Kamphuisen, P., Sijpkens, M., Meijers, J., Buller, H., & Levi, M. (2011). Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects. Circulation, 124(14), 1573-1579. doi:10.1161/circulationaha.111.029017
  7. Fawole, A., Daw, H., & Crowther, M. (2013). Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban. Cleveland Clinic Journal Of Medicine, 80(7), 443-451. doi:10.3949/ccjm.80a.13025
  8. Ferrandis, R., Castillo, J., de Andrés, J., Gomar, C., Gómez-Luque, A., & Hidalgo, F. et al. (2013). The perioperative management of new direct oral anticoagulants: a question without answers. Thromb Haemost, 110(3), 515-522. doi:10.1160/th12-11-0868
  9. Gordon, J., Fabian, T., Lee, M., & Dugdale, M. (2013). Anticoagulant and antiplatelet medications encountered in emergency surgery patients. Journal Of Trauma And Acute Care Surgery, 75(3), 475-486. doi:10.1097/ta.0b013e3182a07391
  10. Hankey, G., & Eikelboom, J. (2011). Dabigatran Etexilate: A New Oral Thrombin Inhibitor. Circulation, 123(13), 1436-1450. doi:10.1161/circulationaha.110.004424
  11. Herrmann, R., Thom, J., Wood, A., Phillips, M., Muhammad, S., & Baker, R. (2013). Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban. Thromb Haemost, 111(5), 989-995. doi:10.1160/th13-07-0607
  12. James, R., Palys, V., Lomboy, J., Lamm, J., & Simon, S. (2013). The role of anticoagulants, antiplatelet agents, and their reversal strategies in the management of intracerebral hemorrhage. Neurosurgical Focus, 34(5), E6. doi:10.3171/2013.2.focus1328
  13. Kaatz, S., & Crowther, M. (2013). Reversal of target-specific oral anticoagulants. J Thromb Thrombolysis, 36(2), 195-202. doi:10.1007/s11239-013-0923-y
  14. Kasliwal, M., Panos, N., Munoz, L., Moftakhar, R., Lopes, D., & Byrne, R. (2014). Outcome following intracranial hemorrhage associated with novel oral anticoagulants. Journal Of Clinical Neuroscience. doi:10.1016/j.jocn.2014.04.025
  15. Khoo, T., Weatherburn, C., Kershaw, G., Reddel, C., Curnow, J., & Dunkley, S. (2012). The use of FEIBA® in the correction of coagulation abnormalities induced by dabigatran. International Journal Of Laboratory Hematology, 35(2), 222-224. doi:10.1111/ijlh.12005
  16. Lai, A., Davidson, N., Galloway, S., & Thachil, J. (2014). Perioperative management of patients on new oral anticoagulants. British Journal Of Surgery, 101(7), 742-749. doi:10.1002/bjs.9485
  17. Lambe, S. (2013). Reversing the New Anticoagulants. Retrieved 7 September 2014, from ../docss/24LambeTheNewAnticoagulants.pdf
  18. Lazo-Langner, A., Lang, E., & Douketis, J. (2013). Clinical review: Clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications. Critical Care, 17(3), 230. doi:10.1186/cc12592
  19. Levine, M., & Goldstein, J. (2014). Emergency Reversal of Anticoagulation: Novel Agents. Current Neurology And Neuroscience Reports, 14(8). doi:10.1007/s11910-014-0471-7
  20. Luddington, R., & Baglin, T. (2004). Clinical measurement of thrombin generation by calibrated automated thrombography requires contact factor inhibition. Journal Of Thrombosis And Haemostasis, 2(11), 1954--1959.
  21. Majeed, A., & Schulman, S. (2013). Bleeding and antidotes in new oral anticoagulants. Best Practice & Research Clinical Haematology, 26(2), 191-202. doi:10.1016/j.beha.2013.07.001
  22. Mancl, E., Crawford, A., & Voils, S. (2012). Contemporary Anticoagulation Reversal: Focus on Direct Thrombin Inhibitors and Factor Xa Inhibitors. Journal Of Pharmacy Practice, 26(1), 43-51. doi:10.1177/0897190012465989
  23. Miller, M., Trujillo, T., & Nordenholz, K. (2014). Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants. The American Journal Of Emergency Medicine, 32(4), 375-382. doi:10.1016/j.ajem.2013.11.044
  24. Mittal, M., & Rabinstein, A. (2012). Anticoagulation-Related Intracranial Hemorrhages. Current Atherosclerosis Reports, 14(4), 351-359. doi:10.1007/s11883-012-0258-8
  25. Nitzki-George, D., Wozniak, I., & Caprini, J. (2013). Current State of Knowledge on Oral Anticoagulant Reversal Using Procoagulant Factors. Annals Of Pharmacotherapy, 47(6), 841-855. doi:10.1345/aph.1r724
  26. Peacock, W., Gearhart, M., & Mills, R. (2012). Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants. Clin Cardiol, 35(12), 730-737. doi:10.1002/clc.22037
  27. Pernod, G., Albaladejo, P., Godier, A., Samama, C., Susen, S., & Gruel, Y. et al. (2013). 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. Archives Of Cardiovascular Diseases, 106(6-7), 382-393. doi:10.1016/j.acvd.2013.04.009
  28. Perzborn, E., Heitmeier, S., Laux, V., & Buchmüller, A. (2014). Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thrombosis Research, 133(4), 671-681. doi:10.1016/j.thromres.2014.01.017
  29. Pollack, C. (2013). Managing Bleeding in Anticoagulated Patients in the Emergency Care Setting. The Journal Of Emergency Medicine, 45(3), 467-477. doi:10.1016/j.jemermed.2013.03.016
  30. Siegal, D., Garcia, D., & Crowther, M. (2014). How I treat target-specific oral anticoagulant-associated bleeding. Blood, 123(8), 1152-1158. doi:10.1182/blood-2013-09-529784
  31. Yates, S., & Sarode, R. (2013). Novel thrombin and factor Xa inhibitors. Current Opinion In Hematology, 20(6), 552-557. doi:10.1097/moh.0b013e328365a164
  32. Zumberg, M., Rajasekhar, A., Lawson, M., & Khanna, A. (2013). . Retrieved 7 September 2014, from ../docss/Anticoag-reversal-in-ICH-2013-2.pdf