Venous Thromboembolism Prophylaxis in Spontaneous Intracerebral Hemorrhage - An Analysis of Ultra-Early and Early Intervention versus Late Management Approaches: A Systematic Review and Meta-Analysis.

Introduction: Spontaneous intracerebral hemorrhage (sICH) is a medical condition associated with significant complications. Mortality, hematoma expansion, and venous thromboembolism (VTE) are critical concerns related to sICH. The timing for prophylaxis of VTE continues to be a matter of concern in medical practice, and there is a lack of solid evidence available, especially regarding the risk of hematoma expansion or poor outcomes when initiated early. Hence, this systematic review and meta-analysis were conducted to evaluate the safety of early and ultra-early heparin prophylaxis by comparing rates of hematoma expansion and mortality in patients with spontaneous intracerebral hemorrhage (sICH) between those receiving ultra-early and early prophylaxis versus late prophylaxis.

Methods: Following the PRISMA guidelines, this study searched Pubmed, Web of Science, Cochrane, and Embase. Inclusion criteria encompassed studies exploring ultra-early ( < 24h), early (>24h - < 48h), and late (48h>) prophylaxis. Effect sizes were calculated using odds ratios (OR) with 95% confidence intervals, and heterogeneity was assessed via I² statistics. The analysis was conducted utilizing RStudio.

Results: The analysis combined results from five studies. All five studies provided data on hematoma expansion, and four of them also included information on mortality rates. Examining hematoma expansion in 1005 patients, including 440 who underwent early and ultra-early interventions, no significant difference was observed, yielding an OR 0.93 (95% CI 0.61 to 1.40, I² 0%). Analyzing mortality rates in 770 patients, including 293 subjected to early and ultra-early interventions, an OR 0.61 (95% CI 0.39 to 0.97, I² 0%) was revealed, indicating a reduction in mortality with ultra-early and early prophylaxis compared to late prophylaxis.

Conclusion : Our study shed light on the safety of the prophylaxis of VTE in sICH by comparing early and ultra-early heparin prophylaxis versus late prophylaxis. The analysis showed no difference regarding hematoma expansion and decreased mortality in the early and ultra-early groups.