Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke.

crit care
Yip HK, Tsai TH, Lin HS, Chen SF, Sun CK, Leu S, Yuen CM, Tan TY, Lan MY, Liou CW, Lu CH, Chang WN.

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INTRODUCTION: Erythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.

METHODS: In total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48h and 72h after acute IS, or serve as placebo (group 2). Circulating level of EPCs [double-stained markers: CD31/CD34 (E1), CD62E/CD34 (E2) and KDR/CD34 (E3)] was determined using flow cytometry at 48h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.

RESULTS: Circulating EPC (E1-E3) level at 48h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48h and on day 7 after IS, EPC (E1-E3) level did not differ between groups 1 and 2 (all P > 0.1). However, by day 21, EPC (E1-E3) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy [95% confidence interval (CI), 0.153 to 0.730; P = 0.006] and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) level were significantly and independently predictive of reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale [greater than or equal to] 8, or death). CONCLUSIONS: EPO therapy significantly improved circulating EPC level and 90-day MANE.

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