Abstract
Background: Early recurrence (ER) of acute ischemic stroke (AIS) and symptomatic intracerebral hemorrhage (SICH) after intravenous thrombolysis (IVT) using alteplse could contribute to unfavorable functional outcome and mortality. Previous studies showed that plasma D-dimer levels reflect fibrin turnover, and are related to early stroke progression and unfavorable functional outcome. Objective: The aim of this study was to investigate whether D-dimer elevation after IVT is a determinant of ER or SICH in AIS. Methods: We measured plasma D-dimer levels twice just before and basically within 24 h after IVT in patients with AIS from January 2011 to December 2017. Patients were divided into quartiles based on the difference in the pre- and post-IVT levels of D-dimer. ER was defined as a new ischemic lesion on MRI with the occurrence of new neurological symptoms. SICH was diagnosed by CT or MRI, combined with an increase of ≥1 point from the baseline NIHSS score. Unfavorable outcome was defined as mRS≥3 at discharge. Results: Of a total of 619 patients (374 men, 74.8±12.2 years old), 37 developed ER and 25 patients SICH. Second D-dimer samples were taken 15.3 hours (median) after IVT. Median baseline and second D-dimer levels were 1.3 (IQR, 0.7-2.5). Second D-dimer levels, measured 15.3 hours (median) after IVT, were 3.6 in median (IQR 1.6-8.5) mg/dl. Median difference of d-dimer was 2.0 (IQR 0.5-6.8) mg/dl. D-dimer difference was significantly associated with ER (p <0.001 for trend), SICH (p =0.007 for trend), and unfavorable outcome (p <0.001 for trend). After adjustment for sex, age, onset-to-needle time, large vessel occlusion, hypertension, diabetes mellitus, atrial fibrillation, baseline NIHSS score, use of anticoagulants within 24 hours from IVT, odds ratios (95% CI) of the highest quartile (≥6.8 mg/dl) were 7.00 (2.17-31.6) for ER, 3.56 (1.52-8.72) for SICH, compared with the lowest quartile (<0.5mg/dl). Similar trends appeared in 349 patients with cardioembolic stroke [11.6 (2.81-80.7) for ER, 12.0 (1.92-238.1) for SICH]. Conclusions: In acute ischemic stroke patients, D-dimer elevation after intravenous thrombolysis was an independent predictor of early recurrence or symptomatic intracerebral hemorrhage.
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