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Peer-reviewedCC BYFrontiers in medicine

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

  • Huan Liang1
  • Baiyu Zeng2
  • Jingquan Wang3
  • Lizhen Yi1
  • Linxing Huang4
  • Ziyan Lin1
  • Cai Zhou3
  • Zenghui Yue1
4 affiliations
  1. 1College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine , ,
  2. 2Teaching and Research Office of TCM Internal Medicine, Hunan Traditional Chinese Medical College , ,
  3. 3Changsha Central Hospital , , ,
  4. 4School of Physical Education, Hunan University of Arts and Science , ,
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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.

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Cite

BibTeXRIS
BibTeX
@article{liang2026cumulative,
  title = {{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}},
  author = {Huan Liang and Baiyu Zeng and Jingquan Wang and Lizhen Yi and Linxing Huang and Ziyan Lin and Cai Zhou and Zenghui Yue},
  journal = {Frontiers in medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fmed.2026.1977632},
  url = {https://europepmc.org/article/PMC/PMC13716756},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - 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
AU  - Huan Liang
AU  - Baiyu Zeng
AU  - Jingquan Wang
AU  - Lizhen Yi
AU  - Linxing Huang
AU  - Ziyan Lin
AU  - Cai Zhou
AU  - Zenghui Yue
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in medicine
DO  - 10.3389/fmed.2026.1977632
UR  - https://europepmc.org/article/PMC/PMC13716756
AB  - 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.
SN  - 2296-858X
ER  -