Risk factors for hemorrhagic transformation after tenecteplase therapy in acute ischemic stroke

This retrospective observational study evaluated the incidence, subtypes, and risk factors for hemorrhagic transformation (HT) after tenecteplase-tissue plasminogen activator (TNK-tPA) therapy in patients with acute ischemic stroke. Adults with acute ischemic stroke who received intravenous TNK-tPA between June 2022 and June 2025 and had complete baseline data and follow-up neuroimaging were included. All patients underwent routine follow-up computed tomography or magnetic resonance imaging at 24 ± 6 hours after thrombolysis, with additional earlier imaging when neurological deterioration occurred. Demographic characteristics, vascular risk factors, baseline neurological severity assessed by the National Institutes of Health Stroke Scale, blood pressure, pre-stroke antiplatelet use, onset-to-needle time, Alberta Stroke Program Early CT Score, and admission laboratory parameters - including white blood cell count, hemoglobin, platelet count, international normalized ratio, fibrinogen, and D-dimer (mg/L fibrinogen-equivalent units) - were collected. HT was classified as hemorrhagic infarction (HI-1, HI-2) or parenchymal hematoma (PH-1, PH-2) according to European Cooperative Acute Stroke Study criteria. Among 181 TNK-tPA-treated patients, 28 (15.5%) developed HT, including 17 cases of HI and 11 of PH. In an exploratory multivariable logistic regression model, older age, higher baseline National Institutes of Health Stroke Scale, lower Alberta Stroke Program Early CT Score, higher systolic blood pressure, and increased international normalized ratio and D-dimer levels were associated with HT. The model showed acceptable apparent calibration and discrimination (area under the receiver operating characteristic curve = 0.86); however, 14 candidate variables were evaluated for only 28 events (approximately 2 events per variable), creating a substantial risk of overfitting. These findings are hypothesis-generating and require validation in larger independent cohorts.