Scientific Publications by FDA Staff

J Thromb Haemost 2006 Jun;4(6):1296-302

Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome.

Simak J, Gelderman MP, Yu H, Wright V, Baird AE

Simak J, US FDA, CBER, Lab Cellular Hematol, HFM-335,1401 Rockville Pike, Rockville, MD 20852 USA US FDA, CBER, Lab Cellular Hematol, Rockville, MD 20852 USA NINDS, Struct Neurosci Unit, NIH, Bethesda, MD 20892 USA

Background: Endothelial membrane microparticles (EMP) in plasma are elevated in several vascular diseases. Objectives: To test the hypothesis that EMP would be increased in patients with acute ischemic stroke and would correlate with stroke severity, brain lesion volume and outcome. Patients and methods: Forty-one patients were studied and divided into two groups based on the National Institutes of Health Stroke Scale (NIHSS) score: 20 patients with mild stroke (NIHSS score < 5) and 21 patients with moderate-severe stroke (NIHSS score >/= 5). Lesion volume was measured using diffusion-weighted magnetic resonance imaging and discharge outcome was based on the discharge Barthel and Rankin scores. Twenty-three age-matched control subjects were also studied. Using flow cytometry, endoglin-positive EMP: CD105(+) CD41a(-)CD45(-) (E(+)EMP), specific endothelial EMP expressing VE-cadherin and endoglin: CD105(+)CD144(+) (C(+)EMP), EMP expressing phosphatidylserine: CD105(+)PS(+) CD41a(-) (PS(+)EMP) and EMP expressing ICAM-1: CD105(+)CD54(+) CD45(-) (I(+)EMP) were analyzed. Results: Significantly higher PS(+)EMP counts were observed in the group of acute ischemic stroke patients [median 59 (25th-75th percentile: 28-86) MP muL(-1)] relative to the controls [28 (14-36) MP muL(-1)] (P = 0.002). All four EMP phenotypes studied were elevated in the subgroup of moderate-severe stroke patients relative to the controls (all P < 0.05). In the patients with acute ischemic stroke three EMP phenotypes (E(+)EMP, PS(+)EMP and I(+)EMP) correlated significantly with brain lesion volume, with I(+)EMP (P = 0.002) showing the strongest correlation. Admission counts of C(+)EMP (P = 0.0003) and E(+)EMP (P = 0.003) correlated significantly with discharge clinical outcome. Conclusions: Certain circulating EMP phenotypes may be associated with severity, lesion volume and outcome of acute ischemic stroke. EMP analysis shows promising contribution to understanding stroke pathophysiology.