Clinical, laboratory, and imaging predictors of hemorrhagic transformation after intravenous thrombolysis in ischemic stroke

Abstract

Background: Ischemic stroke is a leading cause of morbidity and mortality worldwide, with intravenous thrombolysis using alteplase representing the main reperfusion therapy. However, hemorrhagic transformation (HT) after thrombolysis is a serious complication associated with disruption of the blood–brain barrier, microvascular dysfunction, and reperfusion injury. This event is frequently linked to early neurological deterioration and increased mortality. Identifying predictive factors for HT is essential for risk stratification and for improving therapeutic safety in patients undergoing thrombolytic treatment. Objective: To analyze clinical, laboratory, and neuroimaging factors associated with hemorrhagic transformation in patients undergoing intravenous thrombolysis for ischemic stroke. Methods: A systematic review was conducted according to PRISMA guidelines, using the PubMed and Scopus databases. Studies published between 2013 and 2026 were searched using the following descriptors: “ischemic stroke” AND “thrombolysis” AND “hemorrhagic transformation” AND “predictors”. A total of 144 studies were initially identified, of which 12 were selected after title and abstract screening. Following the application of eligibility criteria and full-text review, 8 studies were included in the final analysis. Results: The analyzed studies consistently demonstrated an association between hyperglycemia, greater initial neurological severity (higher NIHSS scores), and an increased risk of hemorrhagic transformation following thrombolysis. Clinical conditions such as atrial fibrillation and diabetes mellitus were also frequently reported as relevant risk factors. In neuroimaging, lower ASPECTS scores, extensive areas of hypodensity, and significant leukoaraiosis were associated with a higher probability of HT, suggesting increased microvascular vulnerability. These findings highlight the importance of integrating clinical, laboratory, and radiological parameters in the assessment of hemorrhagic risk. Conclusion: Metabolic factors — particularly hyperglycemia and diabetes mellitus — together with greater initial neurological severity and neuroimaging abnormalities are associated with a higher risk of hemorrhagic transformation in patients with ischemic stroke treated with intravenous thrombolysis. Identification of these predictors may improve risk stratification and support safer therapeutic decision-making in clinical practice.