Temporal dynamics of microparticle elevation following subarachnoid hemorrhage

Laboratory investigation

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Object

Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH.

Methods

On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden.

Results

When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)−, CD66b+(neutrophil)−, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])–associated MPs and CD146+(endothelial cell)–associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH.

Conclusions

Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)–associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Abbreviations used in this paper:DCI = delayed cerebral ischemia; eNOS = endothelial nitric oxide synthase; GOS-E = extended Glasgow Outcome Scale; MP = microparticle; mRS = modified Rankin Scale; NO = nitric oxide; PHD = posthemorrhage day; SAH = subarachnoid hemorrhage; TCD = transcranial Doppler; TF = tissue factor; vWF = von Willebrand factor.
Article Information

Contributor Notes

Address correspondence to: Matthew R. Sanborn, M.D., Department of Neurosurgery, Perelman School of Medicine at the Hospital of the University of Pennsylvania, 3400 Spruce Street, 3rd Floor Silverstein, Philadelphia, Pennsylvania 19104. email: Matthew.Sanborn@uphs.upenn.edu.Please include this information when citing this paper: published online July 13, 2012; DOI: 10.3171/2012.6.JNS111163.
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