Meta-analysis of Haematoma Volume, Haematoma Expansion and Mortality in Intracerebral Haemorrhage Associated with Oral Anticoagulant Use

Overview

Journal J Neurol

Specialty Neurology

Date 2019 Sep 22

PMID 31541341

Citations 28

Authors

David J Seiffge

Martina B Goeldlin

Turgut Tatlisumak

Philippe Lyrer

Urs Fischer

Stefan T Engelter

David J Werring

Affiliations

Soon will be listed here.

Abstract

Objective: To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.

Methods: We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.

Results: We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.

Conclusion: This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.

Citing Articles

Association of oral anticoagulants with risk of brain haemorrhage expansion compared to no-anticoagulation.

Veltkamp R, Haas K, Rucker V, Malzahn U, Heeger A, Kinzler D Neurol Res Pract. 2025; 7(1):12.

PMID: 39934933 DOI: 10.1186/s42466-024-00358-9.

Possible limited justification for systematic head computed tomography scans based solely on antithrombotic therapy in elderly patients (aged 75 or older) with mild traumatic brain injury.

Jaffres E, Dacher J, Taalba M, Roca F, Garnier M, Normant S Res Diagn Interv Imaging. 2025; 13:100053.

PMID: 39897447 PMC: 11786775. DOI: 10.1016/j.redii.2024.100053.

Association of Prior Antithrombotic Drug Use with 90-Day Mortality After Intracerebral Hemorrhage.

Jorgensen C, Boe N, Hald S, Meyer-Kristensen F, Norlen M, Ovesen C Clin Epidemiol. 2024; 16:837-848.

PMID: 39654831 PMC: 11627103. DOI: 10.2147/CLEP.S493499.

[Focus neurological intensive care medicine 2023/2024 : Summary of selected studies in intensive medical care].

Michalski D, Jungk C, Beynon C, Brenner T, Nusshag C, Reuss C Anaesthesiologie. 2024; 74(1):38-49.

PMID: 39633141 DOI: 10.1007/s00101-024-01490-6.

Intracerebral haemorrhage - mechanisms, diagnosis and prospects for treatment and prevention.

Seiffge D, Fandler-Hofler S, Du Y, Goeldlin M, Jolink W, Klijn C Nat Rev Neurol. 2024; 20(12):708-723.

PMID: 39548285 DOI: 10.1038/s41582-024-01035-w.

References

Rizos T, Jenetzky E, Herweh C, Hug A, Hacke W, Steiner T . Point-of-care reversal treatment in phenprocoumon-related intracerebral hemorrhage. Ann Neurol. 2010; 67(6):788-93. DOI: 10.1002/ana.21965. View

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339:b2700. PMC: 2714672. DOI: 10.1136/bmj.b2700. View

Flibotte J, Hagan N, ODonnell J, Greenberg S, Rosand J . Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004; 63(6):1059-64. DOI: 10.1212/01.wnl.0000138428.40673.83. View

Parry-Jones A, Di Napoli M, Goldstein J, Schreuder F, Tetri S, Tatlisumak T . Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage. Ann Neurol. 2015; 78(1):54-62. PMC: 4654243. DOI: 10.1002/ana.24416. View

Yamashita S, Kimura K, Iguchi Y, Shibazaki K . Prior oral antithrombotic therapy is associated with early death in patients with supratentorial intracerebral hemorrhage. Intern Med. 2011; 50(5):413-9. DOI: 10.2169/internalmedicine.50.4239. View

Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P . Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke. 2008; 39(11):2993-6. DOI: 10.1161/STROKEAHA.108.520668. View

Rosand J, Eckman M, Knudsen K, Singer D, Greenberg S . The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004; 164(8):880-4. DOI: 10.1001/archinte.164.8.880. View

Steiner T, Salman R, Beer R, Christensen H, Cordonnier C, Csiba L . European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014; 9(7):840-55. DOI: 10.1111/ijs.12309. View

Salazar C, Del Aguila D, Cordova E . Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation. Cochrane Database Syst Rev. 2014; (3):CD009893. PMC: 8928929. DOI: 10.1002/14651858.CD009893.pub2. View

10.

Langhorne P, Fearon P, Ronning O, Kaste M, Palomaki H, Vemmos K . Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis. Stroke. 2013; 44(11):3044-9. DOI: 10.1161/STROKEAHA.113.001564. View

11.

Demchuk A, Dowlatshahi D, Rodriguez-Luna D, Molina C, Silva Blas Y, Dzialowski I . Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012; 11(4):307-14. DOI: 10.1016/S1474-4422(12)70038-8. View

12.

Mh Bruins Slot K, Berge E . Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane Database Syst Rev. 2018; 3:CD008980. PMC: 6494202. DOI: 10.1002/14651858.CD008980.pub3. View

13.

Dowlatshahi D, Demchuk A, Flaherty M, Ali M, Lyden P, Smith E . Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011; 76(14):1238-44. PMC: 3068004. DOI: 10.1212/WNL.0b013e3182143317. View

14.

Flaherty M, Tao H, Haverbusch M, Sekar P, Kleindorfer D, Kissela B . Warfarin use leads to larger intracerebral hematomas. Neurology. 2008; 71(14):1084-9. PMC: 2668872. DOI: 10.1212/01.wnl.0000326895.58992.27. View

15.

Ma M, Meretoja A, Churilov L, Sharma G, Christensen S, Liu X . Warfarin-associated intracerebral hemorrhage: volume, anticoagulation intensity and location. J Neurol Sci. 2013; 332(1-2):75-9. DOI: 10.1016/j.jns.2013.06.020. View

16.

Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T . Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke. 2006; 37(8):2165-7. DOI: 10.1161/01.STR.0000231842.32153.74. View

17.

Anderson C, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C . Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013; 368(25):2355-65. DOI: 10.1056/NEJMoa1214609. View

18.

Curtze S, Strbian D, Meretoja A, Putaala J, Eriksson H, Haapaniemi E . Higher baseline international normalized ratio value correlates with higher mortality in intracerebral hemorrhage during warfarin use. Eur J Neurol. 2014; 21(4):616-22. DOI: 10.1111/ene.12352. View

19.

Lioutas V, Goyal N, Katsanos A, Krogias C, Zand R, Sharma V . Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage. Stroke. 2018; 49(10):2309-2316. PMC: 6386175. DOI: 10.1161/STROKEAHA.118.021979. View

20.

Broderick J, Brott T, Duldner J, Tomsick T, Huster G . Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993; 24(7):987-93. DOI: 10.1161/01.str.24.7.987. View