Work

A cumulative biochemical profile of low uric acid and high total bilirubin is associated with hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke: a retrospective cohort study

Year: 2026

Type: article

Abstract: Background and objective Uric acid and bilirubin are endogenous redox-related metabolites, but their joint association with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) remains uncertain. We examined whether relatively low uric acid and high total bilirubin define a cumulative biochemical profile associated with hemorrhagic risk. Methods In this single-center retrospective cohort, we analyzed 733 patients with verifiable pretreatment uric acid and total bilirubin measurements from an IVT registry. Low uric acid (≤278 μmol/L) and high total bilirubin (≥12.67 μmol/L) contributed one point each to a 0–2 adverse-feature score. Any HT was the primary outcome; parenchymal hematoma (PH) and database-defined symptomatic intracranial hemorrhage (sICH) were secondary outcomes. Analyses used logistic regression, Firth bias-reduced regression, multiple imputation and restricted cubic splines. Results HT occurred in 79/733 patients (10.8%). Observed HT rates were 7.0%, 13.6% and 26.5% across zero, one and two adverse features. Each additional feature was associated with higher odds of HT after covariate adjustment (OR 1.76, 95% CI 1.19–2.60; P = 0.004). PH occurred in 30/733 patients (4.1%), and database-defined sICH occurred in 33/664 patients with observed status (5.0%). Continuous spline analyses in 731 patients showed evidence of an overall association for uric acid ( P overall=0.044) and total bilirubin ( P overall=0.040), without strong evidence of nonlinearity ( P nonlinear=0.193 and P nonlinear=0.704, respectively). No multiplicative interaction between the continuous biomarker terms was detected (OR 0.99, 95% CI 0.77–1.28; P = 0.938). Conclusions Relatively low uric acid and high total bilirubin defined a cumulative biochemical profile associated with greater odds of HT after IVT. The association requires external validation and should not be interpreted as evidence of causality or as a clinical treatment threshold.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1977632