Abstract WP37: Evidence of Late Hemorrhage in Ischemic Stroke Patients Treated With Intravenous Alteplase: A Post Hoc Analysis of the Multicenter MR WITNESS Trial (NCT01282242)

Abstract

Introduction: Although early hemorrhagic transformation (HT) in acute ischemic stroke has been studied, less is known about patients who develop hemorrhage after the acute phase. We hypothesized that patients with late hemorrhage (LH) would have more severe strokes than those without, and tested this hypothesis in a cohort of thrombolysed patients from the MR WITNESS trial. Methods: Subjects were recruited from 10 sites between Jan 2011-Oct 2015. MR WITNESS enrolled subjects if they were last seen between 4.5 and 24 hours prior to evaluation, but otherwise qualified for IV tPA in the 3-4.5 hr window per AHA guidelines, and if their brain MRI findings indicated very early infarction: either no FLAIR hyperintensity or subtle hyperintensity, ie signal increase <15% compared to the contralateral hemisphere. Patients with early (≤48 hours) HT (defined per ECASS criteria) were excluded from analysis. Late hemorrhage was defined as imaging manifestation of hemorrhage on 30 days MRI in patient without manifestation of HT at 48h. Good outcome was pre-specified as modified Rankin Scale (mRS) 0-1 at 90 d. Univariate comparisons utilized Fisher’s exact test and Wilcoxon Rank Sums 2-sample exact test for categorical and continuous variables, respectively. Results: Among the 80 patients included in the MR WITNESS cohort, 53 met our inclusion criteria and were analysed. When compared to those with no HT, patients with LH had larger baseline infarct volumes and perfusion defects, as well as more frequent proximal vessel occlusion at baseline (all p <0.01, See Table). Patients with LH also demonstrated worse functional outcome at 90 days (mRS, Median [IQR], 3 [1.75-4] vs 1 [0-2], p=0.006, Table). Conclusion: Patients with LH demonstrate a more severe imaging profile at baseline and a worse functional outcome at 90 days when compared to patients without hemorrhage. Understanding the underlying pathophysiology of LH may shed light on to the mechanisms of acute and subacute brain injury.