Background

Optimal timing of pharmacologic venous thromboembolism (VTE) prophylaxis after spontaneous intracerebral hemorrhage (ICH) remains uncertain due to concerns regarding hematoma expansion. Prior studies have primarily relied on arbitrary time thresholds rather than physiological markers of hemorrhage stability.

Objectives

To summarize the literature on the safety and efficacy of pharmacologic VTE prophylaxis initiated after radiographic confirmation of hematoma stability in patients with spontaneous ICH.

Methods

We conducted a systematic review and meta-analysis of studies assessing heparinoids prophylaxis following repeat neuroimaging demonstrating hemorrhage stability. Three databases were searched: PubMed, Embase, Cochrane Central. The meta-analysis was registered in PROSPERO (CRD420261282903). The primary outcome was new or worsening intracranial hemorrhage, including hematoma expansion or new bleeding. Secondary outcomes included deep vein thrombosis and pulmonary embolism. Random-effects models were applied. P value was set at 0.05.

Results

Four observational studies comprising 935 patients met inclusion criteria. Comparative meta-analysis demonstrated no significant association between pharmacologic prophylaxis after radiographic stability and intracranial bleeding risk (OR: 1.24, 95% CI: 0.80-1.94, P = 0.33), with negligible heterogeneity (I² = 0%). Sensitivity analysis restricted to parenchymal hematoma expansion showed similar results (OR 2.37, 95% CI: 0.42-13.43, P = 0.33). Thromboembolic outcomes trended in favor of pharmacological prophylaxis without reaching statistical significance (OR: 0.63, 95% CI: 0.33-1.22, P = 0.17).

Conclusions

Pharmacologic VTE prophylaxis initiated after radiographic confirmation of hematoma stability does not increase intracranial hemorrhage risk and may reduce thromboembolic complications. These findings support further investigation into imaging-guided, individualized strategies for pharmacologic VTE prophylaxis after ICH.