Timing, safety, and efficacy of initiating anticoagulation in intracranial surgery: a systematic review and meta-analysis

BackgroundVenous thromboembolism (VTE) remains a major cause of early postoperative morbidity and mortality after intracranial tumor surgery, yet consensus on the optimal timing of pharmacologic prophylaxis is lacking. MethodsWe conducted a PRISMA-guided systematic review and meta-analysis of randomized and cohort studies evaluating postoperative anticoagulant prophylaxis after brain tumor craniotomy. PubMed, Embase, Web of Science, Scopus, and Cochrane were searched through September 9, 2025. Two reviewers independently screened studies and extracted data; risk of bias was evaluated using JBI tools. Primary and secondary outcomes were VTE, intracranial hemorrhage (ICH), and mortality. Odds ratios (ORs) were pooled using random-effects (REML) models with Hartung-Knapp adjustment. Prespecified sensitivity analyses; leave-one-out, LMWH-only, postoperative-only, UFH vs LMWH subgrouping, and common- vs random-effects models, assessed robustness. ResultsSix studies (seven comparisons) met inclusion criteria. Pharmacologic prophylaxis demonstrated a directionally favorable but non-significant reduction in VTE (OR 0.71, 95% CI 0.35-1.45; I2=28.9%), with no increase in ICH (OR 0.96, 95% CI 0.46-2.00; I2=0%) or mortality (OR 0.74, 95% CI 0.33-1.65; I2=0%). Sensitivity analyses showed strong internal consistency: excluding a mechanistically atypical UFH-based hemodilution study (Moussa 2016) removed all heterogeneity (I2=0%) and yielded pooled effects nearly identical to LMWH-only and postoperative-only models (ORs 0.89-0.92). Apparent funnel-plot asymmetry was resolved upon exclusion of this structural outlier, indicating no meaningful publication bias. ConclusionsAcross available evidence, initiating LMWH prophylaxis 12-72 hours after tumor craniotomy appears to optimize the balance between thrombosis prevention and hemorrhagic safety. Preoperative initiation provides no clear benefit and may increase bleeding risk. Larger, standardized trials are needed to refine timing, dosing, and patient selection.