Hemorrhagic Transformation After Tenecteplase in Patients With Acute Ischemic Stroke: Outcomes of Reversal Therapy

Hemorrhagic transformation (HT) is a serious complication associated with thrombolytic therapies, with high risk of mortality and poor functional outcomes. Despite tenecteplase’s (TNK) higher fibrin specificity compared to alteplase, reversal with cryoprecipitate or human fibrinogen concentrate in TNK-associated HT remains a common practice. This study aimed to evaluate whether TNK reversal with fibrinogen-containing agents impacts clinical outcomes in patient with post-TNK HT.

Retrospective data from the American Heart Association’s Get With The Guidelines–Stroke registry and chart review were analyzed for 70 hospitalized patients across a multicenter health system who received intravenous TNK for acute ischemic stroke and developed hemorrhagic transformation within 36 hours between March 2023 and August 2025. The primary outcomes were 90-day modified Rankin Scale (mRS) and the incidences of hematoma expansion, adjudicated by neurologist based on available imaging studies. The secondary outcomes will include associations between patient demographic and clinical characteristics and the risk of developing HT post-thrombolytics.

Of the 70 included patients, 11 (15.7%) were reversed with either cryoprecipitate or human fibrinogen concentrate and 59 (84.3%) did not received reversal. The median fibrinogen level prior to reversal was 446 mg/dL and 511mg/dL post-reversal. The reversal group had significantly shorter time interval between TNK administration and development of HT compared with the no-reversal group (3.8 vs. 15 hours; p < 0.001). Higher proportion of patients in the reversal group had developed symptomatic intracranial hemorrhage (sICH) prior to the intervention (90.9% vs. 47.5%; p = 0.008). Functional outcomes were similar at 90 days, with median mRS of 4.5 and 4, respectively (p= 0.516). Mortality rates were 36.4% in the reversal group and 18.6% in the no-reversal group (p = 0.910). Hospital length of stay was similar between the 2 groups (10.1 vs. 10.4 days; p= 0.910) and disposition status did not differ significantly (p = 0.303).

Reversal of TNK with fibrinogen-containing agents was not associated with improved 90-day mRS or reduced mortality in patients who developed HT. These findings suggest that routine administration of reversal therapy may not be associated with clinical benefits in post-TNK HT.