Efficacy of rt-PA versus Urokinase in early time windows for minimally invasive intracerebral hemorrhage evacuation and exploratory TAFI pharmacogenomics.

BACKGROUND: Minimally invasive hematoma evacuation with local thrombolysis is increasingly used for spontaneous intracerebral hemorrhage (ICH), yet comparative data on thrombolytic agents across early time windows remain limited. Whether the thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism modulates thrombolytic efficacy in this setting is unknown. METHODS: We conducted a retrospective comparative cohort study involving 120 patients with supratentorial ICH. Following minimally invasive hematoma aspiration, patients were treated with either rt-PA (n = 60) or urokinase (n = 60). Each group was stratified by onset-to-surgery time into ultra-acute (3 to 6 h), acute (6 to 24 h), and subacute (24 to 72 h) subgroups. Neurological and functional outcomes, hematoma clearance, perihematomal edema, and TAFI genotypes were analyzed. Pre-specified exploratory subgroup analyses by dominant hemisphere and by hematoma volume stratum (30-50 mL vs. 51-80 mL) were also performed. Effect sizes with 95% confidence intervals (CIs) are reported alongside p-values, and the Bonferroni method was applied to control the family-wise error rate for primary between-group comparisons. RESULTS: rt-PA was associated with better neurological and functional outcomes than urokinase from discharge onward across all three time windows (all Bonferroni-adjusted p < 0.017), with higher hematoma clearance and lower perihematomal edema. The difference in 3-month NIHSS score within the ultra-acute subgroup was 5.24 points (95% CI: 4.30-6.18; Cohen's d = 4.06). Ultra-acute treatment produced the most favorable outcomes regardless of agent. The TAFI Ile325 (TT) genotype was enriched in the ultra-acute rt-PA subgroup (80.00% vs. 22.22% acute and 29.63% subacute; p = 0.009; odds ratio for TT carriage vs. urokinase in the ultra-acute subgroup = 10.00 [95% CI: 1.80-55.71]) and positively correlated with hematoma clearance in that window (r = 0.670, p = 0.006). No genotype-outcome association was observed with urokinase. CONCLUSION: rt-PA was associated with more favorable outcomes than urokinase for minimally invasive ICH evacuation in this retrospective cohort, with the ultra-acute window conferring the greatest benefit. The TAFI Ile325 genotype may represent a candidate pharmacogenomic marker for enhanced rt-PA response during this early period. These hypothesis-generating findings require validation in prospective, multicenter studies.