Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage

BACKGROUND: Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage?

METHODS: (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature.

RESULTS: In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation (P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, (P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19).

CONCLUSIONS: LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.