University of Oulu

C. Qian, J. Huhtakangas, S. Juvela, M.K. Bode, T. Tatlisumak, M. Savolainen, H. Numminen, J. Ollikainen, L. Luostarinen, L. Kupila, S. Tetri, Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study, Clinical Neurology and Neurosurgery, Volume 202, 2021, 106534, ISSN 0303-8467,

Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH : a double blind placebo controlled multicenter study

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Author: Qian, C.1; Huhtakangas, J.2; Juvela, S.3;
Organizations: 1Department of Neurosurgery, Oulu University Hospital, Oulu, Finland
2Department of Neurology, Oulu University Hospital, Oulu, Finland
3Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland
4Department of Radiology, Oulu University Hospital, Oulu, Finland
5Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
6Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
7Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
8Department of Neurology, South Karelian Central Hospital, Lappeenranta, Finland
9Department of Neurology, Tampere University Hospital, Finland
10Department of Neurology, Päijät-Häme Central Hospital, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-05-07


Background: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients.

Methods: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge.

Results: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups.

Conclusion: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.

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Series: Clinical neurology and neurosurgery
ISSN: 0303-8467
ISSN-E: 1872-6968
ISSN-L: 0303-8467
Volume: 202
Article number: 106534
DOI: 10.1016/j.clineuro.2021.106534
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: TT received academic grants for ICH research from Helsinki University Central Hospital, University of Gothenburg, Sahlgrenska University Hospital, and Sigrid Juselius Foundation. ST received academic grants from Finnish Medical Foundations.
Copyright information: © 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (