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Neurological Research and Practice
Published in: Neurological Research and Practice 1/2019

Open Access 01-12-2019 | Stroke | Review

Resumption of oral anticoagulation after spontaneous intracerebral hemorrhage

Authors: Jochen A. Sembill, Joji B. Kuramatsu, Stefan Schwab, Hagen B. Huttner

Published in: Neurological Research and Practice | Issue 1/2019

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Abstract

Background

Given an ageing population the incidence of both patients suffering from intracerebral hemorrhage (ICH) and those requiring oral anticoagulation will increase. Up to now there are no results from randomized trials available whether or not, and when, ICH survivors should resume OAC. This review summarizes the most important observational studies, and initiated ongoing trials, to help guiding physicians in daily routine decision making.

Findings

Several large observational studies and meta-analyses verified that OAC resumption was associated with a significant reduction of thromboembolic complications and mortality without leading to increased rates of recurrent ICH. OAC resumption seemed further associated with improved functional recovery and favorable long-term outcome. Given the general bleeding risk reduction in patients using Non–vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin-K-antagonist (VKA), NOAC use should also be preferred after ICH, although specific comparative studies are pending. Patients with lobar ICH need special attention as these patients showed increased ICH recurrence rates, why decision making should include extended diagnostic work-up evaluating cerebral microbleed burden, cortical subarachnoid hemorrhage and superficial siderosis. Further, patients with mechanical heart valves need specific consideration as restarting VKA may be unsafe until two weeks, whereas optimal balancing of hemorrhagic with thromboembolic complications may allow earlier re-initiation one week after ICH. In patients with atrial fibrillation, resumption generally should take place between 4 and 8 weeks after ICH depending on a patient’s individual risk profile. Left atrial appendage occlusion (LAAO) might represent an alternative strategy in high-risk patients. Ongoing clinical trials will clarify whether OAC resumption versus LAAO versus no antithrombotic therapy may represent the best possible secondary stroke prevention in ICH survivors with atrial fibrillation.

Conclusions

According to observational data OAC resumption after ICH seems beneficial and safe. Ongoing clinical trials will create evidence regarding treatment effects of pharmaceutical resumption and interventional alternatives. Yet, individual decision making weighing the patient’s individual thromboembolic versus hemorrhagic risks remains essential.
Literature
1.
Biffi, A., Anderson, C. D., Battey, T. W., Ayres, A. M., Greenberg, S. M., Viswanathan, A., et al. (2015). Association between blood pressure control and risk of recurrent intracerebral hemorrhage. Jama, 314(9), 904–912.CrossRefPubMedPubMedCentral
2.
Biffi, A., Kuramatsu, J. B., Leasure, A., Kamel, H., Kourkoulis, C., Schwab, K., et al. (2017). Oral anticoagulation and functional outcome after intracerebral hemorrhage. Annals of Neurology, 82(5), 755–765.CrossRefPubMedPubMedCentral
3.
Chai-Adisaksopha, C., Iorio, A., Hillis, C., Siegal, D., Witt, D. M., Schulman, S., et al. (2017). Warfarin resumption following anticoagulant-associated intracranial hemorrhage: A systematic review and meta-analysis. Thrombosis Research, 160, 97–104.CrossRefPubMed
4.
Chao, T. F., Liu, C. J., Liao, J. N., Wang, K. L., Lin, Y. J., Chang, S. L., et al. (2016). Use of Oral anticoagulants for stroke prevention in patients with atrial fibrillation who have a history of intracranial hemorrhage. Circulation, 133(16), 1540–1547.CrossRefPubMed
5.
Charidimou, A., Boulouis, G., Gurol, M. E., Ayata, C., Bacskai, B. J., Frosch, M. P., et al. (2017). Emerging concepts in sporadic cerebral amyloid angiopathy. Brain, 140(7), 1829–1850.CrossRefPubMedPubMedCentral
6.
Charidimou, A., Boulouis, G., Roongpiboonsopit, D., Auriel, E., Pasi, M., Haley, K., et al. (2017). Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study. Neurology, 89(21), 2128–2135.CrossRefPubMedPubMedCentral
7.
Charidimou, A., Boulouis, G., Xiong, L., Jessel, M. J., Roongpiboonsopit, D., Ayres, A., et al. (2017). Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology, 88(17), 1607–1614.CrossRefPubMedPubMedCentral
8.
Charidimou, A., Imaizumi, T., Moulin, S., Biffi, A., Samarasekera, N., Yakushiji, Y., et al. (2017). Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis. Neurology, 89(8), 820–829.CrossRefPubMedPubMedCentral
9.
Charidimou, A., Karayiannis, C., Song, T. J., Orken, D. N., Thijs, V., Lemmens, R., et al. (2017). Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF. Neurology, 89(23), 2317–2326.CrossRefPubMed
10.
Chatterjee, S., Sardar, P., Biondi-Zoccai, G., & Kumbhani, D. J. (2013). New oral anticoagulants and the risk of intracranial hemorrhage: Traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurology, 70(12), 1486–1490.PubMed
11.
Eikelboom, J. W., Connolly, S. J., Brueckmann, M., Granger, C. B., Kappetein, A. P., Mack, M. J., et al. (2013). Dabigatran versus warfarin in patients with mechanical heart valves. The New England Journal of Medicine, 369(13), 1206–1214.CrossRefPubMed
12.
Gage, B. F., van Walraven, C., Pearce, L., Hart, R. G., Koudstaal, P. J., Boode, B. S., et al. (2004). Selecting patients with atrial fibrillation for anticoagulation: Stroke risk stratification in patients taking aspirin. Circulation, 110(16), 2287–2292.CrossRefPubMed
13.
Gerner, S. T., Kuramatsu, J. B., Sembill, J. A., Sprugel, M. I., Endres, M., Haeusler, K. G., et al. (2018). Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Annals of Neurology, 83(1), 186–196.CrossRefPubMed
14.
Halvorsen, S., Storey, R. F., Rocca, B., Sibbing, D., Ten Berg, J., Grove, E. L., et al. (2017). Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: Expert consensus paper of the European Society of Cardiology Working Group on thrombosis. European Heart Journal, 38(19), 1455–1462.PubMed
15.
Hawryluk, G. W., Austin, J. W., Furlan, J. C., Lee, J. B., O'Kelly, C., & Fehlings, M. G. (2010). Management of anticoagulation following central nervous system hemorrhage in patients with high thromboembolic risk. Journal of Thrombosis and Haemostasis, 8(7), 1500–1508.CrossRefPubMed
16.
Hemphill, J. C., 3rd, Greenberg, S. M., Anderson, C. S., Becker, K., Bendok, B. R., Cushman, M., et al. (2015). Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 46(7), 2032–2060.CrossRefPubMed
17.
Holmes, D. R., Jr., Kar, S., Price, M. J., Whisenant, B., Sievert, H., Doshi, S. K., et al. (2014). Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. Journal of the American College of Cardiology, 64(1), 1–12.CrossRefPubMed
18.
Holmes, D. R., Reddy, V. Y., Turi, Z. G., Doshi, S. K., Sievert, H., Buchbinder, M., et al. (2009). Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: A randomised non-inferiority trial. Lancet, 374(9689), 534–542.CrossRefPubMed
19.
Inohara, T., Xian, Y., Liang, L., Matsouaka, R. A., Saver, J. L., Smith, E. E., et al. (2018). Association of Intracerebral Hemorrhage among Patients Taking non-Vitamin K Antagonist vs vitamin K antagonist Oral anticoagulants with in-hospital mortality. JAMA, 319(5), 463–473.CrossRefPubMedPubMedCentral
20.
Katsanos, A. H., Schellinger, P. D., Kohrmann, M., Filippatou, A., Gurol, M. E., Caso, V., et al. (2018). Fatal oral anticoagulant-related intracranial hemorrhage: A systematic review and meta-analysis. European Journal of Neurology, 25(10), 1299–1302.CrossRefPubMed
21.
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., et al. (2016). 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal, 37(38), 2893–2962.CrossRefPubMed
22.
Korompoki, E., Filippidis, F. T., Nielsen, P. B., Del Giudice, A., Lip, G. Y. H., Kuramatsu, J. B., et al. (2017). Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation. Neurology, 89(7), 687–696.CrossRefPubMedPubMedCentral
23.
Krishnamurthi, R. V., Feigin, V. L., Forouzanfar, M. H., Mensah, G. A., Connor, M., Bennett, D. A., et al. (2013). Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: Findings from the global burden of disease study 2010. The Lancet Global Health, 1(5), e259–e281.CrossRefPubMedPubMedCentral
24.
Kuramatsu, J. B., Gerner, S. T., Schellinger, P. D., Glahn, J., Endres, M., Sobesky, J., et al. (2015). Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA, 313(8), 824–836.CrossRefPubMed
25.
Kuramatsu, J. B., & Huttner, H. B. (2019). Management of oral anticoagulation after intracerebral hemorrhage. International Journal of Stroke, 14(3), 238–246.CrossRefPubMed
26.
Kuramatsu, J. B., Sembill, J. A., Gerner, S. T., Sprugel, M. I., Hagen, M., Roeder, S. S., et al. (2018). Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves. European Heart Journal, 39(19), 1709–1723.CrossRefPubMedPubMedCentral
27.
Linn, J., Halpin, A., Demaerel, P., Ruhland, J., Giese, A. D., Dichgans, M., et al. (2010). Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology, 74(17), 1346–1350.CrossRefPubMedPubMedCentral
28.
Majeed, A., Kim, Y. K., Roberts, R. S., Holmstrom, M., & Schulman, S. (2010). Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke, 41(12), 2860–2866.CrossRefPubMed
29.
Murphy, M. P., Kuramatsu, J. B., Leasure, A., Falcone, G. J., Kamel, H., Sansing, L. H., et al. (2018). Cardioembolic stroke risk and recovery after anticoagulation-related intracerebral hemorrhage. Stroke, 49(11), 2652–2658.CrossRefPubMed
30.
Murthy, S. B., Gupta, A., Merkler, A. E., Navi, B. B., Mandava, P., Iadecola, C., et al. (2017). Restarting anticoagulant therapy after intracranial hemorrhage: A systematic review and meta-analysis. Stroke, 48(6), 1594–1600.CrossRefPubMedPubMedCentral
31.
Nielsen-Kudsk, J. E., Johnsen, S. P., Wester, P., Damgaard, D., Airaksinen, J., Lund, J., et al. (2017). Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage: A propensity score-matched follow-up study. EuroIntervention, 13(3), 371–378.CrossRefPubMed
32.
Nielsen, P. B., Larsen, T. B., Skjoth, F., Gorst-Rasmussen, A., Rasmussen, L. H., & Lip, G. Y. (2015). Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: A Nationwide cohort study. Circulation, 132(6), 517–525.CrossRefPubMed
33.
Nishimura, R. A., Otto, C. M., Bonow, R. O., Carabello, B. A., Erwin, J. P., 3rd, Fleisher, L. A., et al. (2017). 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the Management of Patients with Valvular Heart Disease: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation, 135(25), e1159–e1195.CrossRefPubMed
34.
Ottosen, T. P., Grijota, M., Hansen, M. L., Brandes, A., Damgaard, D., Husted, S. E., et al. (2016). Use of antithrombotic therapy and long-term clinical outcome among patients surviving intracerebral hemorrhage. Stroke, 47(7), 1837–1843.CrossRefPubMed
35.
Park, Y. A., Uhm, J. S., Pak, H. N., Lee, M. H., & Joung, B. (2016). Anticoagulation therapy in atrial fibrillation after intracranial hemorrhage. Heart Rhythm, 13(9), 1794–1802.CrossRefPubMed
36.
Pennlert, J., Overholser, R., Asplund, K., Carlberg, B., Van Rompaye, B., Wiklund, P. G., et al. (2017). Optimal timing of anticoagulant treatment after intracerebral hemorrhage in patients with atrial fibrillation. Stroke, 48(2), 314–320.CrossRefPubMed
37.
Pisters, R., Lane, D. A., Nieuwlaat, R., de Vos, C. B., Crijns, H. J., & Lip, G. Y. (2010). A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The euro heart survey. Chest, 138(5), 1093–1100.CrossRefPubMed
38.
Purrucker, J. C., Haas, K., Rizos, T., Khan, S., Wolf, M., Hennerici, M. G., et al. (2016). Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new Oral anticoagulants. JAMA Neurology, 73(2), 169–177.CrossRefPubMed
39.
40.
Reddy, V. Y., Mobius-Winkler, S., Miller, M. A., Neuzil, P., Schuler, G., Wiebe, J., et al. (2013). Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: The ASAP study (ASA Plavix feasibility study with Watchman left atrial appendage closure technology). Journal of the American College of Cardiology, 61(25), 2551–2556.CrossRefPubMed
41.
Rodrigues, M. A., Samarasekera, N., Lerpiniere, C., Humphreys, C., McCarron, M. O., White, P. M., et al. (2018). The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: Model development and diagnostic test accuracy study. Lancet Neurology, 17(3), 232–240.CrossRefPubMed
42.
Roongpiboonsopit, D., Charidimou, A., William, C. M., Lauer, A., Falcone, G. J., Martinez-Ramirez, S., et al. (2016). Cortical superficial siderosis predicts early recurrent lobar hemorrhage. Neurology, 87(18), 1863–1870.CrossRefPubMedPubMedCentral
43.
Schellinger, P. D., Tsivgoulis, G., Steiner, T., & Kohrmann, M. (2018). Percutaneous left atrial appendage occlusion for the prevention of stroke in patients with atrial fibrillation: Review and critical appraisal. J Stroke, 20(3), 281–291.CrossRefPubMedPubMedCentral
44.
Sembill, J. A., Gerner, S. T., Volbers, B., Bobinger, T., Lucking, H., Kloska, S. P., et al. (2017). Severity assessment in maximally treated ICH patients: The max-ICH score. Neurology, 89(5), 423–431.CrossRefPubMed
45.
Sembill, J. A., Huttner, H. B., & Kuramatsu, J. B. (2018). Impact of recent studies for the treatment of intracerebral hemorrhage. Current Neurology and Neuroscience Reports, 18(10), 71.CrossRefPubMed
46.
Sembill, J. A., Wieser, C. Y., Sprugel, M. I., Gerner, S. T., Giede-Jeppe, A., Reindl, C., et al. (2018). Initiating anticoagulant therapy after ICH is associated with patient characteristics and treatment recommendations. Journal of Neurology, 265(10), 2404–2414.CrossRefPubMed
47.
Shoamanesh, A., Kwok, C. S., & Benavente, O. (2011). Cerebral microbleeds: Histopathological correlation of neuroimaging. Cerebrovascular Diseases, 32(6), 528–534.CrossRefPubMed
48.
Steiner, T., Al-Shahi Salman, R., Beer, R., Christensen, H., Cordonnier, C., Csiba, L., et al. (2014). European stroke organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. International Journal of Stroke.
49.
Tsivgoulis, G., Lioutas, V. A., Varelas, P., Katsanos, A. H., Goyal, N., Mikulik, R., et al. (2017). Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage. Neurology, 89(11), 1142–1151.CrossRefPubMed
50.
Vahanian, A., Alfieri, O., Andreotti, F., Antunes, M. J., Baron-Esquivias, G., Baumgartner, H., et al. (2012). Guidelines on the management of valvular heart disease (version 2012). European Heart Journal, 33(19), 2451–2496.CrossRefPubMed
51.
van Asch, C. J., Luitse, M. J., Rinkel, G. J., van der Tweel, I., Algra, A., & Klijn, C. J. (2010). Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis. Lancet Neurology, 9(2), 167–176.CrossRefPubMed
52.
van Etten, E. S., Gurol, M. E., van der Grond, J., Haan, J., Viswanathan, A., Schwab, K. M., et al. (2016). Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy. Neurology, 87(14), 1482–1487.CrossRefPubMedPubMedCentral
53.
Vestergaard, A. S., Skjoth, F., Lip, G. Y., & Larsen, T. B. (2016). Effect of anticoagulation on hospitalization costs after intracranial hemorrhage in atrial fibrillation: A registry study. Stroke, 47(4), 979–985.CrossRefPubMed
54.
Wardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., et al. (2013). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurology, 12(8), 822–838.CrossRefPubMedPubMedCentral
55.
Wolfe, Z., Khan, S. U., Nasir, F., Raghu Subramanian, C., & Lash, B. (2018). A systematic review and Bayesian network meta-analysis of risk of intracranial hemorrhage with direct oral anticoagulants. Journal of Thrombosis and Haemostasis, 16(7), 1296–1306.CrossRefPubMed
56.
Yung, D., Kapral, M. K., Asllani, E., Fang, J., & Lee, D. S. (2012). Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: The best practice for reinitiating anticoagulation therapy after intracranial bleeding (BRAIN) study. The Canadian Journal of Cardiology, 28(1), 33–39.CrossRefPubMed
57.
Zhou, Z., Yu, J., Carcel, C., Delcourt, C., Shan, J., Lindley, R. I., et al. (2018). Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: Systematic review and meta-analysis. BMJ Open, 8(5), e019672.CrossRefPubMedPubMedCentral
Metadata
Title
Resumption of oral anticoagulation after spontaneous intracerebral hemorrhage
Authors
Jochen A. Sembill
Joji B. Kuramatsu
Stefan Schwab
Hagen B. Huttner
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Neurological Research and Practice / Issue 1/2019
Electronic ISSN: 2524-3489
DOI
https://doi.org/10.1186/s42466-019-0018-0

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