Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage
Authors: Sprügel Maximilian I , Sembill Jochen A , Kuramatsu Joji B , Gerner Stefan T , Hagen Manuel , Roeder Sebastian S , Endres Matthias , Haeusler Karl Georg , Sobesky Jan , Schurig Johannes , Zweynert Sarah , Bauer Miriam , Vajkoczy Peter , Ringleb Peter Arthur , Purrucker Jan Christoph , Rizos Timolaos , Volkmann Jens , Muellges Wolfgang , Kraft Peter , Schubert Anna-Lena , Erbguth Frank , Nueckel Martin , Schellinger Peter D , Glahn Jörg , Knappe Ulrich J , Fink Gereon Rudolf , Dohmen Christian , Stetefeld Henning , Fisse Anna Lena , Minnerup Jens , Hagemann Georg , Rakers Florian , Reichmann Heinz , Schneider Hauke , Wöpking Sigrid , Ludolph Albert C , Stösser Sebastian , Neugebauer Hermann , Röther Joachim , Michels Peter , Schwarz Michael , Reimann Gernot , Bäzner Hansjörg , Schwert Henning , Classen Joseph , Michalski Dominik , Grau Armin , Palm Frederick , Urbanek Christian , Wöhrle Johannes C , Alshammari Fahid , Horn Markus , Bahner Dirk , Witte Otto W , Guenther Albrecht , Hamann Gerhard F , Lücking Hannes , Dörfler Arnd , Schwab Stefan , Huttner Hagen B 
Published: April 2019

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.