title: The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage.
abstract: Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI.
  
  
  
  A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt-Hess (HH) 1-3] versus severe (HH 4-5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated.
  
  
  
  We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4-6 OR 1.18, 95 % CI 1.05-1.32, P = 0.007) and CRP (mRS4-6 OR 1.02, 95 % CI 1.00-1.03, P = 0.041).
  
  
  
  Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.
authors.affiliation: Cerebrovascular Center of the Neurological Institute, Cleveland Clinic, 9500 Euclid Ave. S80, Cleveland, OH, 44195, USA. frontej@ccf.org.|Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. frontej@ccf.org.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Frontera
authors.affiliation: Department of Neurology and Neuroscience, Brain Immunology and Glia Center, University of Virginia, Charlottesville, VA, USA.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Provencio
authors.affiliation: Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Fatima A
authors.initials: FA
authors.lastname: Sehba
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: McIntyre
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Nowacki
authors.affiliation: Department of Critical Care, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Errol
authors.initials: E
authors.lastname: Gordon
authors.affiliation: Cerebrovascular Center of the Neurological Institute, Cleveland Clinic, 9500 Euclid Ave. S80, Cleveland, OH, 44195, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Weimer
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Aledort
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001930:Brain Injuries / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D015539:Platelet Activation / Q000502:physiology*; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Early brain injury; Inflammation; Microthrombosis; Platelet; SAH; Subarachnoid hemorrhage