Temporal dynamics of microparticle elevation following subarachnoid hemorrhage.
OBJECTIVE
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.
Department of Neurosurgery, Institute for Environmental Medicine, Perelman School of Medicine at the Universityof Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Matthew.Sanborn@uphs.upenn.edu
Matthew R
MR
Sanborn
Stephen R
SR
Thom
Leif-Erik
LE
Bohman
Sherman C
SC
Stein
Joshua M
JM
Levine
Tatyana
T
Milovanova
Eileen
E
Maloney-Wilensky
Suzanne
S
Frangos
Monisha A
MA
Kumar
D000328:Adult; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000453:epidemiology*; D051929:CD146 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000276:immunology / Q000378:metabolism*; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000453:epidemiology*; D005500:Follow-Up Studies; D023261:Glasgow Outcome Scale; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000150:complications*; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D014463:Ultrasonography
D051929:CD146 Antigen; D013925:Thromboplastin