Effect of heparin for the prevention of venous thromboembolism in patients with spontaneous intracranial cerebral hemorrhage: a meta-analysis

Venous thromboembolism (VTE) has a serious impact on the prognosis of patients with spontaneous intracranial hemorrhage (sICH). However, the use of prophylactic heparin remains controversial.

This study investigated the safety and timing of prophylactic heparin for VTE in patients with sICH.

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.

Two authors systematically searched Web of Science, Cochrane Library, Embase, and PubMed to find all published research before June 2023. The incidence of deep venous thrombosis (DVT) and mortality were set as primary endpoints.

This meta-analysis included seven randomized controlled trials (RCTs) and five observational studies involving a total of 4419 sICH patients in the heparin (n = 2808) and control (n = 1183) groups. Among these patients, 205 received early heparin administration, while 223 received late heparin administration. The results suggested that, compared to the control group, patients in the heparin group had a lower incidence of VTE [odds ratio (OR), 0.47; 95% CI, 0.31–0.71; p < 0.001], DVT (OR, 0.53; 95% CI, 0.33–0.85; p = 0.009), pulmonary embolism (OR, 0.31 95% CI, 0.15–0.65; p = 0.002), and mortality (OR, 0.70; 95% CI, 0.54–0.90; p = 0.006), but there were no statistical differences in hematoma enlargement, extracranial hematoma, and major disability (p > 0.05). There was no statistically significant difference in DVT, mortality, hematoma enlargement, and extracranial hemorrhage between the early heparin group (<24–48 h) and the late heparin group (p > 0.05).

In patients with sICH, prophylactic use of heparin may be beneficial because it reduces the incidence of VTE and mortality without increasing the risk of additional bleeding. In addition, early prophylactic use of heparin appears to be safe. However, large-scale RCTs are lacking to support this evidence.