Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage

Sprügel M, Sembill J, Kuramatsu J, Gerner S, Hagen M, Röder S, Endres M, Haeusler KG, Sobesky J, Schurig J, Zweynert S, Bauer M, Vajkoczy P, Ringleb PA, Purrucker JC, Rizos T, Volkmann J, Muellges W, Kraft P, Schubert AL, Erbguth F, Nueckel M, Schellinger PD, Glahn J, Knappe UJ, Fink GR, Dohmen C, Stetefeld H, Fisse AL, Minnerup J, Hagemann G, Rakers F, Reichmann H, Schneider H, Wöpking S, Ludolph AC, Stösser S, Neugebauer H, Röther J, Michels P, Schwarz M, Reimann G, Bäzner H, Schwert H, Classen J, Michalski D, Grau A, Palm F, Urbanek C, Wöhrle JC, Alshammari F, Horn M, Bahner D, Witte OW, Guenther A, Hamann GF, Lücking H, Dörfler A, Schwab S, Huttner H (2019)

Publication Type: Journal article

Publication year: 2019

Journal

DOI: 10.1136/jnnp-2018-319786

Abstract

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. Results: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. Conclusions: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Authors with CRIS profile

Involved external institutions

Paracelsus Medizinische Privatuniversität, Nürnberg Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Johannes Wesling Klinikum Minden Germany (DE) NeuroCure Cluster of Excellence at the Charité Germany (DE) Friedrich-Schiller-Universität Jena Germany (DE) Universität Leipzig Germany (DE) Gemeinschaftsklinikum Mittelrhein Germany (DE) Universität zu Köln Germany (DE) Fachklinik für Neurologie Dietenbronn GmbH Germany (DE) HELIOS Kliniken Germany (DE) Technische Universität Dresden Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Klinikum Stuttgart Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Bezirkskrankenhaus Günzburg Germany (DE) Klinikum Dortmund Germany (DE) Klinikum der Stadt Ludwigshafen am Rhein gGmbH Germany (DE)

How to cite

APA:

Sprügel, M., Sembill, J., Kuramatsu, J., Gerner, S., Hagen, M., Röder, S.,... Huttner, H. (2019). Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage. Journal of Neurology Neurosurgery and Psychiatry. https://dx.doi.org/10.1136/jnnp-2018-319786

MLA:

Sprügel, Maximilian, et al. "Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage." Journal of Neurology Neurosurgery and Psychiatry (2019).

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