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Patients on NOACs in the Emergency Room

  • Stroke (H.C. Diener, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Despite the increasing use of NOACs, there is still uncertainty on how to treat NOAC patients presenting with neurological emergencies. Initial assessment of coagulation status is challenging but essential in these patients to provide best-possible treatment in case of ischemic or hemorrhagic stroke. Meanwhile, anticoagulation reversal strategies have been suggested; yet, the optimal management is still unestablished. The current review aims to provide up-to-date information on (i) how to identify patients with NOAC intake, (ii) which therapies are feasible in the setting of ischemic and hemorrhagic stroke as well as traumatic intracranial hemorrhage, and (iii) how to proceed with patients requiring emergency lumbar puncture.

Recent Findings

Despite several expert opinions, there is still an ongoing debate which NOAC patients presenting with ischemic stroke may benefit from recanalizing strategies and whether these treatment approaches can be performed safely. Results from two phase IV trials investigating the efficacy of NOAC-specific reversal agents in case of major bleeding seem promising with regard to hemostatic parameters, but these antidotes have not been verified to clinically benefit patients, and approval by authorities in parts is still pending.

Summary

Specific reversal agents are on the way and will provide new treatment options in patients with NOAC-related ischemic and hemorrhagic stroke. Up to now, the decision which patients should undergo recanalizing treatment for ischemic stroke, or which specific pharmacological reversal treatment in hemorrhagic stroke should be initiated, has to be made cautiously on an individual basis after assessing hemostatic parameters.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Steinberg BA, Gao H, Shrader P, Pieper K, Thomas L, Camm AJ, et al. International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries. Am Heart J. 2017;194:132–40. https://doi.org/10.1016/j.ahj.2017.08.011 Observational data from three OAC registries reporting an increase of NOAC-use in AF-patients.

    Article  CAS  PubMed  Google Scholar 

  2. Loo SY, Dell'Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol. 2017;83(9):2096–106. https://doi.org/10.1111/bcp.13299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Apenteng PN, Gao H, Hobbs FR, Fitzmaurice DA. Temporal trends in antithrombotic treatment of real-world UK patients with newly diagnosed atrial fibrillation: findings from the GARFIELD-AF registry. BMJ Open. 2018;8(1):e018905. https://doi.org/10.1136/bmjopen-2017-018905.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mekaj YH, Mekaj AY, Duci SB, Miftari EI. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag. 2015;11:967–77. https://doi.org/10.2147/TCRM.S84210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–62. https://doi.org/10.1016/S0140-6736(13)62343-0.

    Article  CAS  PubMed  Google Scholar 

  6. Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2017;48(9):2494–503. https://doi.org/10.1161/STROKEAHA.117.017549.

    Article  CAS  PubMed  Google Scholar 

  7. Cha MJ, Choi EK, Han KD, Lee SR, Lim WH, Oh S, et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017;48(11):3040–8. https://doi.org/10.1161/STROKEAHA.117.018773.

    Article  CAS  PubMed  Google Scholar 

  8. Lopez-Lopez JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058. https://doi.org/10.1136/bmj.j5058.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014;6:213–20. https://doi.org/10.2147/clep.s47385.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ganetsky M. Trends and characteristics of emergency department patients prescribed novel oral anticoagulants. J Emerg Med. 2015;49(5):693–7. https://doi.org/10.1016/j.jemermed.2015.04.028.

    Article  PubMed  Google Scholar 

  11. •• Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, 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):1330–93. https://doi.org/10.1093/eurheartj/ehy136 Very helpful and practical guide for management of AF patients with NOAC therapy.

    Article  CAS  PubMed  Google Scholar 

  12. Seiffge DJ, Kagi G, Michel P, Fischer U, Bejot Y, Wegener S, et al. Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage. Ann Neurol. 2018;83(3):451–9. https://doi.org/10.1002/ana.25165.

    Article  CAS  PubMed  Google Scholar 

  13. Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, 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):2137–49. https://doi.org/10.1093/eurheartj/ehw058.

    Article  CAS  PubMed  Google Scholar 

  14. Douxfils J, Chatelain C, Chatelain B, Dogne JM, Mullier F. Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost. 2013;110(2):283–94. https://doi.org/10.1160/th12-12-0898.

    Article  CAS  PubMed  Google Scholar 

  15. Morishima Y, Kamisato C. Laboratory measurements of the oral direct factor Xa inhibitor edoxaban: comparison of prothrombin time, activated partial thromboplastin time, and thrombin generation assay. Am J Clin Pathol. 2015;143(2):241–7. https://doi.org/10.1309/ajcpq2njd3pxftug.

    Article  CAS  PubMed  Google Scholar 

  16. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, 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):1116–27. https://doi.org/10.1160/th09-11-0758.

    Article  Google Scholar 

  17. Douxfils J, Mullier F, Loosen C, Chatelain C, Chatelain B, Dogne JM. Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendations for 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.

    Article  CAS  PubMed  Google Scholar 

  18. Shin H, Cho MC, Kim RB, Kim CH, Choi NC, Kim SK, et al. Laboratory measurement of apixaban using anti-factor Xa assays in acute ischemic stroke patients with non-valvular atrial fibrillation. J Thromb Thrombolysis. 2018;45(2):250–6. https://doi.org/10.1007/s11239-017-1590-1.

    Article  CAS  PubMed  Google Scholar 

  19. Baglin T, Keeling D, Kitchen S. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: guidance from the British Committee for Standards in Haematology. Br J Haematol. 2012;159(4):427–9. https://doi.org/10.1111/bjh.12052.

    Article  CAS  PubMed  Google Scholar 

  20. Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol. 2014;64(11):1128–39. https://doi.org/10.1016/j.jacc.2014.05.065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ebner M, Birschmann I, Peter A, Hartig F, Spencer C, Kuhn J, et al. Emergency coagulation assessment during treatment with direct oral anticoagulants: limitations and solutions. Stroke. 2017;48(9):2457–63. https://doi.org/10.1161/STROKEAHA.117.017981.

    Article  PubMed  Google Scholar 

  22. Douxfils J, Chatelain B, Chatelain C, Dogne JM, Mullier F. Edoxaban: impact on routine and specific coagulation assays. A practical laboratory guide. Thromb Haemost. 2016;115(2):368–81. https://doi.org/10.1160/th15-05-0415.

    Article  PubMed  Google Scholar 

  23. Purrucker JC, Haas K, Rizos T, Khan S, Poli S, Kraft P, et al. Coagulation testing in acute ischemic stroke patients taking non-vitamin K antagonist oral anticoagulants. Stroke. 2017;48(1):152–8. https://doi.org/10.1161/STROKEAHA.116.014963.

    Article  CAS  PubMed  Google Scholar 

  24. Salmonson T, Dogné J-M, Janssen H, Garcia Burgos J, Blake P. 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):42–7. https://doi.org/10.1093/ehjcvp/pvw032.

    Article  PubMed  Google Scholar 

  25. • Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory monitoring of non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation: a review. JAMA Cardiol. 2017;2(5):566–74. https://doi.org/10.1001/jamacardio.2017.0364 Helpful review of coagulation assessment and its interpretation in patients with NOAC therapy.

    Article  PubMed  Google Scholar 

  26. • Ebner M, Birschmann I, Peter A, Hartig F, Spencer C, Kuhn J, et al. Limitations of specific coagulation tests for direct oral anticoagulants: a critical analysis. J Am Heart Assoc. 2018;7(19):e009807. https://doi.org/10.1161/JAHA.118.009807 Critical study investigating different specific coagulation assays for detection of relevant NOAC concentrations.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, Weitz JI. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost : JTH. 2016;14(3):623–7. https://doi.org/10.1111/jth.13227.

    Article  CAS  PubMed  Google Scholar 

  28. Ahmed N, Steiner T, Caso V, Wahlgren N. participants E-Ks. Recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 13-15 November 2016. Eur Stroke J. 2017;2(2):95–102. https://doi.org/10.1177/2396987317699144.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ebner M, Birschmann I, Peter A, Spencer C, Hartig F, Kuhn J, et al. Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants. Crit Care. 2017;21(1):32. https://doi.org/10.1186/s13054-017-1619-z.

    Article  PubMed  PubMed Central  Google Scholar 

  30. • Pollack CV. Coagulation assessment with the new generation of oral anticoagulants. Emerg Med J. 2016;33(6):423–30. https://doi.org/10.1136/emermed-2015-204891 Detailed overview of coagulation assays used in NOAC patients and its interpretation.

    Article  PubMed  Google Scholar 

  31. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.

    Article  Google Scholar 

  32. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation--developed with the special contribution of the European Heart Rhythm Association. Europace. 2012;14(10):1385–413. https://doi.org/10.1093/europace/eus305.

    Article  PubMed  Google Scholar 

  33. Forslund T, Komen JJ, Andersen M, Wettermark B, von Euler M, Mantel-Teeuwisse AK, et al. Improved stroke prevention in atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants. Stroke. 2018;49(9):2122–8. https://doi.org/10.1161/strokeaha.118.021990.

    Article  CAS  PubMed  Google Scholar 

  34. Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol. 2017;69(23):2779–90. https://doi.org/10.1016/j.jacc.2017.03.600.

    Article  CAS  PubMed  Google Scholar 

  35. Audebert H, Hellwig S, Haeusler KG, Endres M, Grittner U. Non-vitamin K-dependent oral anticoagulants have a positive impact on ischaemic stroke severity in patients with atrial fibrillation. EP Europace. 2017;20(4):569–74. https://doi.org/10.1093/europace/eux087.

    Article  Google Scholar 

  36. Hoyer C, Filipov A, Neumaier-Probst E, Szabo K, Ebert A, Alonso A. Impact of pre-admission treatment with non-vitamin K oral anticoagulants on stroke severity in patients with acute ischemic stroke. J Thromb Thrombolysis. 2018;45(4):529–35. https://doi.org/10.1007/s11239-018-1634-1.

    Article  CAS  PubMed  Google Scholar 

  37. Jung YH, Choi HY, Lee KY, Cheon K, Han SW, Park JH, et al. Stroke severity in patients on non-vitamin K antagonist oral anticoagulants with a standard or insufficient dose. Thromb Haemost. 2018;118(12):2145–51. https://doi.org/10.1055/s-0038-1675602.

    Article  PubMed  Google Scholar 

  38. Park JH, Han SW, Lee K-Y, Choi H-Y, Cheon K, Cho H-J, et al. Impact of non-vitamin K antagonist oral anticoagulant withdrawal on stroke outcomes. Front Neurol. 2018;9:1095. https://doi.org/10.3389/fneur.2018.01095.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tomita H, Hagii J, Metoki N, Saito S, Shiroto H, Hitomi H, et al. Severity and functional outcome of patients with cardioembolic stroke occurring during non-vitamin K antagonist oral anticoagulant treatment. J Stroke Cerebrovasc Dis. 2015;24(6):1430–7. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.004.

    Article  PubMed  Google Scholar 

  40. Saver JL, Goyal M, Bonafe A, Diener H-C, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285–95. https://doi.org/10.1056/NEJMoa1415061.

    Article  CAS  PubMed  Google Scholar 

  41. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309(23):2480–8. https://doi.org/10.1001/jama.2013.6959.

    Article  CAS  PubMed  Google Scholar 

  42. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384(9958):1929–35. https://doi.org/10.1016/s0140-6736(14)60584-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. •• Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611–22. https://doi.org/10.1056/NEJMoa1804355 RCT reporting IVT to improve outcomes in MRI-guided selected patients with unknown onset of stroke.

    Article  PubMed  Google Scholar 

  44. • Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573–82. https://doi.org/10.1056/NEJMoa1716405 RCT noting that tenecteplase was superior compared to alteplase before EVT in regards to recanalization rate and functional outcome in ischemic stroke patients treated within 4.5 h.

    Article  CAS  PubMed  Google Scholar 

  45. •• Anderson CS, Robinson T, Lindley RI, Arima H, Lavados PM, Lee T-H, et al. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med. 2016;374(24):2313–23. https://doi.org/10.1056/NEJMoa1515510 RCT compared low- (0.6 mg/kg BW) vs. normal-dose rt-PA for IVT in predominantly Asian stroke patients, reported lower rates of IVT-related hemorrhagic complications.

    Article  CAS  PubMed  Google Scholar 

  46. •• Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11–21. https://doi.org/10.1056/NEJMoa1706442 RCT reporting EVT performed up to 24 h after stroke onset improves functional outcome in a CT/MRI-preselected cohort.

    Article  PubMed  Google Scholar 

  47. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296–306. https://doi.org/10.1056/NEJMoa1503780.

    Article  CAS  PubMed  Google Scholar 

  48. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019–30. https://doi.org/10.1056/NEJMoa1414905.

    Article  CAS  PubMed  Google Scholar 

  49. Campbell BCV, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–18. https://doi.org/10.1056/NEJMoa1414792.

    Article  CAS  PubMed  Google Scholar 

  50. Berkhemer OA, Fransen PSS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20. https://doi.org/10.1056/NEJMoa1411587.

    Article  CAS  PubMed  Google Scholar 

  51. • Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, Moulin T, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016;15(11):1138–47. https://doi.org/10.1016/S1474-4422(16)30177-6 RCT investigating the combined approach of IVT and EVT compared to IVT alone in ischemic stroke patients in France.

    Article  CAS  PubMed  Google Scholar 

  52. •• Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708–18. https://doi.org/10.1056/NEJMoa1713973 RCT reporting better outcomes in imaging-based selected stroke patients receiving EVT in the extended time window (6–16 h).

    Article  PubMed  Google Scholar 

  53. Campbell BC, Meretoja A, Donnan GA, Davis SM. Twenty-year history of the evolution of stroke thrombolysis with intravenous alteplase to reduce long-term disability. Stroke. 2015;46(8):2341–6. https://doi.org/10.1161/STROKEAHA.114.007564.

    Article  PubMed  Google Scholar 

  54. Fugate JE, Rabinstein AA. Absolute and relative contraindications to IV rt-PA for acute ischemic stroke. Neurohospitalist. 2015;5(3):110–21. https://doi.org/10.1177/1941874415578532.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Yaghi S, Eisenberger A, Willey JZ. Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment. JAMA Neurol. 2014;71(9):1181–5. https://doi.org/10.1001/jamaneurol.2014.1210.

    Article  PubMed  PubMed Central  Google Scholar 

  56. •• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–e110. https://doi.org/10.1161/STR.0000000000000158 Current guideline of the AHA for management of ischemic stroke patients with focus on recanalizing strategies.

    Article  PubMed  Google Scholar 

  57. • Seiffge DJ, Hooff RJ, Nolte CH, Bejot Y, Turc G, Ikenberg B, et al. Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome. Circulation. 2015;132(13):1261–9. https://doi.org/10.1161/CIRCULATIONAHA.115.015484 First study available reporting a safety profile of IVT/EVT in NOAC patients with ischemic stroke similar to that in subtherapeutic VKA and non-anticoagulated patients.

    Article  CAS  PubMed  Google Scholar 

  58. • Seiffge DJ, Traenka C, Polymeris AA, Thilemann S, Wagner B, Hert L, et al. Intravenous thrombolysis in patients with stroke taking rivaroxaban using drug specific plasma levels: experience with a standard operation procedure in clinical practice. J Stroke. 2017;19(3):347–55. https://doi.org/10.5853/jos.2017.00395 Study reporting IVT in rivaroxaban patients with anti-factor Xa levels < 100 ng/ml to be safe.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Giannandrea D, Caponi C, Mengoni A, Romoli M, Marando C, Gallina A, et al. Intravenous thrombolysis in stroke after dabigatran reversal with idarucizumab: case series and systematic review. J Neurol Neurosurg Psychiatry. 2018;90(5):619–23. https://doi.org/10.1136/jnnp-2018-318658.

    Article  PubMed  Google Scholar 

  60. Kermer P, Eschenfelder CC, Diener HC, Grond M, Abdalla Y, Althaus K, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - a national case collection. Int J Stroke. 2017;12(4):383–91. https://doi.org/10.1177/1747493017701944.

    Article  PubMed  Google Scholar 

  61. Diener HC, Bernstein R, Butcher K, Campbell B, Cloud G, Davalos A, et al. Thrombolysis and thrombectomy in patients treated with dabigatran with acute ischemic stroke: expert opinion. Int J Stroke. 2017;12(1):9–12.

    Article  CAS  Google Scholar 

  62. • Xian Y, Federspiel JJ, Hernandez AF, Laskowitz DT, Schwamm LH, Bhatt DL, et al. Use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who take non-vitamin K antagonist oral anticoagulants before stroke. Circulation. 2017;135(11):1024–35. https://doi.org/10.1161/CIRCULATIONAHA.116.023940 Study from the Get with the guidelines registry providing evidence for the safety of IVT in patients with prior NOAC intake.

    Article  CAS  PubMed  Google Scholar 

  63. Jin C, Huang RJ, Peterson ED, Laskowitz DT, Hernandez AF, Federspiel JJ, et al. Intravenous tPA (tissue-type plasminogen activator) in patients with acute ischemic stroke taking non-vitamin K antagonist oral anticoagulants preceding stroke. Stroke. 2018;49(9):2237–40. https://doi.org/10.1161/strokeaha.118.022128.

    Article  CAS  PubMed  Google Scholar 

  64. • Tsivgoulis G, Safouris A. Intravenous thrombolysis in acute ischemic stroke patients pretreated with non-vitamin K antagonist oral anticoagulants: an editorial review. Stroke. 2017;48(7):2031–3. https://doi.org/10.1161/strokeaha.117.017206 Review of IVT in ischemic stroke patients with NOAC intake.

    Article  PubMed  Google Scholar 

  65. •• Goyal M, Menon BK, van Zwam WH, Dippel DWJ, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31. https://doi.org/10.1016/S0140-6736(16)00163-X Meta-analysis of EVT-trials demonstrating the benefit of EVT irrespective of patient characteristics.

    Article  PubMed  Google Scholar 

  66. Liu M, Zheng Y, Li G. Safety of recanalization therapy in patients with acute ischemic stroke under anticoagulation: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2018;27(9):2296–305. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.012.

    Article  PubMed  Google Scholar 

  67. Diener HC, Foerch C, Riess H, Rother J, Schroth G, Weber R. Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment. Lancet Neurol. 2013;12(7):677–88. https://doi.org/10.1016/S1474-4422(13)70101-7.

    Article  CAS  PubMed  Google Scholar 

  68. Purrucker JC, Wolf M, Haas K, Rizos T, Khan S, Dziewas R, et al. Safety of endovascular thrombectomy in patients receiving non-vitamin K antagonist oral anticoagulants. Stroke. 2016;47(4):1127–30. https://doi.org/10.1161/strokeaha.116.012684.

    Article  CAS  PubMed  Google Scholar 

  69. Purrucker JC, Haas K, Wolf M, Rizos T, Khan S, Kraft P, et al. Haemorrhagic transformation after ischaemic stroke in patients taking non-vitamin K antagonist oral anticoagulants. J Stroke. 2017;19(1):67–76. https://doi.org/10.5853/jos.2016.00542.

    Article  PubMed  PubMed Central  Google Scholar 

  70. • Steiner T, Kohrmann M, Schellinger PD, Tsivgoulis G. Non-vitamin k oral anticoagulants associated bleeding and its antidotes. J Stroke. 2018;20(3):292–301. https://doi.org/10.5853/jos.2018.02250 Latest, detailed review of diagnostics and management in patients with NOAC-related ICH.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, et al. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015;36(20):1264–72. https://doi.org/10.1093/eurheartj/ehu463.

    Article  CAS  PubMed  Google Scholar 

  72. Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke. 2012;43(6):1511–7. https://doi.org/10.1161/STROKEAHA.112.650614.

    Article  CAS  PubMed  Google Scholar 

  73. Hankey GJ, Stevens SR, Piccini JP, Lokhnygina Y, Mahaffey KW, Halperin JL, et al. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke. 2014;45(5):1304–12. https://doi.org/10.1161/strokeaha.113.004506.

    Article  CAS  PubMed  Google Scholar 

  74. Wang X, Mondal S, Wang J, Tirucherai G, Zhang D, Boyd RA, et al. Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects. Am J Cardiovasc Drugs : drugs, devices, and other interventions. 2014;14(2):147–54. https://doi.org/10.1007/s40256-013-0055-y.

    Article  CAS  PubMed  Google Scholar 

  75. Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9(7):840–55. https://doi.org/10.1111/ijs.12309.

    Article  PubMed  Google Scholar 

  76. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a Guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032–60. https://doi.org/10.1161/STR.0000000000000069.

    Article  PubMed  Google Scholar 

  77. • Boulouis G, Morotti A, Goldstein JN, Charidimou A. Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials. J Neurol Neurosurg Psychiatry. 2017;88(4):339–45. https://doi.org/10.1136/jnnp-2016-315346 Meta-analysis of randomized controlled trials reporting lower rates of hematoma enlargement in ICH patients receiving acute blood pressure lowering.

    Article  PubMed  Google Scholar 

  78. • Gerner ST, Kuramatsu JB, Sembill JA, Sprugel MI, Endres M, Haeusler KG, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol. 2018;83(1):186–96. https://doi.org/10.1002/ana.25134 Multicenter, observational study reporting no influence of PCC administration on hematoma enlargement or outcome in patients with NOAC-related ICH.

    Article  CAS  PubMed  Google Scholar 

  79. Purrucker JC, Haas K, Rizos T, Khan S, Wolf M, Hennerici MG, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2016;73(2):169–77. https://doi.org/10.1001/jamaneurol.2015.3682.

    Article  PubMed  Google Scholar 

  80. Wilson D, Seiffge DJ, Traenka C, Basir G, Purrucker JC, Rizos T, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology. 2017;88(18):1693–700. https://doi.org/10.1212/WNL.0000000000003886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gerner ST, Kuramatsu JB, Schwab S, Huttner HB. Abstract TP420: clinical and imaging characteristics in NOAC-related intracerebral hemorrhage. Stroke. 2019;50(Suppl_1):ATP420-ATP. https://doi.org/10.1161/str.50.suppl_1.TP420.

    Article  Google Scholar 

  82. • Tsivgoulis G, Wilson D, Katsanos AH, Sargento-Freitas J, Marques-Matos C, Azevedo E, et al. Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage. Ann Neurol. 2018;84(5):694–704. https://doi.org/10.1002/ana.25342 Meta-analysis of current studies investigating hematoma characteristics and functional outcome in NOAC-related ICH.

    Article  CAS  PubMed  Google Scholar 

  83. • Inohara T, Xian Y, Liang L, Matsouaka RA, Saver JL, Smith EE, et al. Association of intracerebral hemorrhage among patients taking non-vitamin K antagonist vs vitamin K antagonist oral anticoagulants with in-hospital mortality. Jama. 2018;319(5):463–73. https://doi.org/10.1001/jama.2017.21917 Data from the Get with the guidelines registry reporting lower in-hospital mortality in patients with NOAC-related ICH compared to those with VKA-related ICH.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lopes RD, Guimaraes PO, Kolls BJ, Wojdyla DM, Bushnell CD, Hanna M, et al. Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Blood. 2017;129(22):2980–7. https://doi.org/10.1182/blood-2016-08-731638.

    Article  CAS  PubMed  Google Scholar 

  85. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15(5):625–51. https://doi.org/10.1093/europace/eut083.

    Article  PubMed  Google Scholar 

  86. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011;42(12):3594–9. https://doi.org/10.1161/STROKEAHA.111.624650.

    Article  PubMed  Google Scholar 

  87. • Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6–46. https://doi.org/10.1007/s12028-015-0222-x Comprehensive review and practical statement of the NCS and SCCM how to reverse NOAC patients with intracranial hemorrhage.

    Article  CAS  PubMed  Google Scholar 

  88. Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511–20. https://doi.org/10.1056/NEJMoa1502000.

    Article  CAS  Google Scholar 

  89. •• Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017;377(5):431–41. https://doi.org/10.1056/NEJMoa1707278 Multicenter, prospective study investigating the use of idarucizumab for reversal in dabigatran patients with major bleeding or need for urgent procedure.

    Article  CAS  PubMed  Google Scholar 

  90. Connolly SJ, Gibson CM, Crowther M. Andexanet alfa for factor Xa inhibitor reversal. N Engl J Med. 2016;375(25):2499–500. https://doi.org/10.1056/NEJMc1613270.

    Article  PubMed  Google Scholar 

  91. Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413–24. https://doi.org/10.1056/NEJMoa1510991.

    Article  CAS  PubMed  Google Scholar 

  92. •• Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380:1326–35. https://doi.org/10.1056/NEJMoa1814051 Full-study report of the phase IV trial investigating the effect of andexanet α on anti-factor Xa activity and hemostatic efficacy in patients with intake of factor Xa inhibitors.

    Article  CAS  PubMed  Google Scholar 

  93. Pharmaceuticals P. Prescribing information of andexxa. 2018. https://www.portola.com/wp-content/uploads/Andexxa-prescribing-information-pdf.pdf. Accessed 26/03/2019.

  94. • Ansell JE. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis. 2016;41(2):248–52. https://doi.org/10.1007/s11239-015-1288-1 Summary of current and future agents for reversal treatment in patients with NOAC intake.

    Article  CAS  PubMed  Google Scholar 

  95. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371(22):2141–2. https://doi.org/10.1056/NEJMc1411800.

    Article  PubMed  Google Scholar 

  96. • Raval AN, Cigarroa JE, Chung MK, Diaz-Sandoval LJ, Diercks D, Piccini JP, et al. Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation. 2017;135(10):e604–e33. https://doi.org/10.1161/CIR.0000000000000477 Detailed recommendation of the AHA for management of NOAC patients, notably with need for hemostatic reversal.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. • Majdan M, Plancikova D, Brazinova A, Rusnak M, Nieboer D, Feigin V, et al. Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health. 2016;1(2):e76–83. https://doi.org/10.1016/s2468-2667(16)30017-2 Cross-sectional analysis of the epidemiology of TBI in European countries in 2012.

    Article  PubMed  Google Scholar 

  98. Hankey Graeme J, Stevens Susanna R, Piccini Jonathan P, Lokhnygina Y, Mahaffey Kenneth W, Halperin Jonathan L, et al. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban. Stroke. 2014;45(5):1304–12. https://doi.org/10.1161/STROKEAHA.113.004506.

    Article  CAS  PubMed  Google Scholar 

  99. Beynon C, Brenner S, Younsi A, Rizos T, Neumann J-O, Pfaff J, et al. Management of patients with acute subdural hemorrhage during treatment with direct oral anticoagulants. Neurocrit Care. 2019;30(2):322–33. https://doi.org/10.1007/s12028-018-0635-4.

    Article  CAS  PubMed  Google Scholar 

  100. Zeeshan M, Jehan F, O'Keeffe T, Khan M, Zakaria ER, Hamidi M, et al. The novel oral anticoagulants (NOACs) have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI. J Trauma Acute Care Surg. 2018;85(5):915–20. https://doi.org/10.1097/TA.0000000000001995.

    Article  CAS  PubMed  Google Scholar 

  101. Prexl O, Bruckbauer M, Voelckel W, Grottke O, Ponschab M, Maegele M, et al. The impact of direct oral anticoagulants in traumatic brain injury patients greater than 60-years-old. Scand J Trauma Resusc Emerg Med. 2018;26(1):20. https://doi.org/10.1186/s13049-018-0487-0.

    Article  PubMed  PubMed Central  Google Scholar 

  102. McMordie JH, Gard AP, Surdell DL, Thorell WE. Aneurysmal subarachnoid hemorrhage in patients taking direct oral anticoagulants: a case series and discussion of management. Interdisciplinary Neurosurg. 2018;11:65–7. https://doi.org/10.1016/j.inat.2017.08.006.

    Article  Google Scholar 

  103. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012;43(6):1711–37. https://doi.org/10.1161/STR.0b013e3182587839.

    Article  PubMed  Google Scholar 

  104. • Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ et al. Guidelines for the management of severe traumatic brain injury, Fourth Edition. Neurosurgery. 2017;80(1):6-15. Doi:https://doi.org/10.1227/neu.0000000000001432. Current guideline for the management of TBI patients provided by the brain-trauma foundation.

  105. • Engelborghs S, Niemantsverdriet E, Struyfs H, Blennow K, Brouns R, Comabella M, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017;8:111–26. https://doi.org/10.1016/j.dadm.2017.04.007 Up-to-date guidelines for the use of lumbar puncture in neurological diseases.

    Article  Google Scholar 

  106. Majed B, Zephir H, Pichonnier-Cassagne V, Yazdanpanah Y, Lestavel P, Valette P, et al. Lumbar punctures: use and diagnostic efficiency in emergency medical departments. Int J Emerg Med. 2009;2(4):227–35. https://doi.org/10.1007/s12245-009-0128-5.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Duits FH, Martinez-Lage P, Paquet C, Engelborghs S, Lleo A, Hausner L, et al. Performance and complications of lumbar puncture in memory clinics: results of the multicenter lumbar puncture feasibility study. Alzheimers Dement. 2016;12(2):154–63. https://doi.org/10.1016/j.jalz.2015.08.003.

    Article  PubMed  Google Scholar 

  108. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368(22):2113–24. https://doi.org/10.1056/NEJMra1206531.

    Article  CAS  PubMed  Google Scholar 

  109. Benzon HT, Avram MJ, Green D, Bonow RO. New oral anticoagulants and regional anaesthesia. Br J Anaesth. 2013;111(Suppl 1):i96–113. https://doi.org/10.1093/bja/aet401.

    Article  CAS  PubMed  Google Scholar 

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Hagen B. Huttner reports personal fees outside the submitted work from Boehringer Ingelheim (dabigatran, idarucizumab), Daiichi Sankyo (edoxaban), and CSL Behring (Beriplex—PCC). He also reports grants from Medtronic, Novartis, and UCB Pharma, outside the submitted work. Stefan T. Gerner declares no potential conflicts of interest.

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Gerner, S.T., Huttner, H.B. Patients on NOACs in the Emergency Room. Curr Neurol Neurosci Rep 19, 40 (2019). https://doi.org/10.1007/s11910-019-0954-7

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