title: Variation in a locus linked to platelet aggregation phenotype predicts intraparenchymal hemorrhagic volume.
abstract: OBJECTIVE
  Alteration in platelet aggregation has been shown to promote bleeding and affect outcome after intracerebral hemorrhage (ICH).We investigated the influence of genetic variants of platelet aggregation, and their effects on admission ICH volume and  clinical outcome.
  
  
  METHODS
  Our prospective study analyzed selected candidate single-nucleotide polymorphisms (SNPs) previously associated with platelet aggregation phenotype in previous genome-wide association studies, with regards to outcome and ICH volume. Patients were assessed  at the Columbia University Medical Center Neuro-Intensive Care Unit. Exclusion criteria included age <18 years, ICH following trauma, hemorrhagic transformation, or tumor, no consent for genetic analysis, or incomplete data. Radiological variables (location and volume of acute ICH, presence  of intraventricular extension, midline shift, and hydrocephalus) and clinical variables (mortality and modified Rankin score at discharge) were prospectively recorded.
  
  
  RESULTS
  One hundred and twenty-two patients with spontaneous ICH between February 2009 and May 2011 diagnosed via  clinical assessment and admission computed tomography scan were included. The median admission Glasgow coma scale score (GCS) was 11·5. Univariate predictors of mortality at discharge included systolic blood pressure, presence of intraventricular hemorrhage, anticoagulant use, and GCS,  the only independent predictor of discharge mortality (P<0·001). Age, intraventricular hemorrhage, and GCS were associated with poor functional outcome; age (P = 0·001) and GCS (P<0·001) were significant in the multivariate model. Admission  GCS (P<0·01), antiplatelet use, and rs342286 (PIK3CG; P = 0·04; R(2) = 0·247) had univariate associations with hematoma volume.
  
  
  CONCLUSIONS
  We identified SNP rs342286 as an independent predictor of admission  hematoma volume. Our findings suggest that PIK3CG function, which is previously linked to this SNP and affects platelet aggregation, impacts the severity of the intraparenchymal bleed.
authors.affiliation: Cerebrovascular Laboratory Columbia University, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. gappelbo@gmail.com
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Appelboom
authors.forename: Matthew
authors.initials: M
authors.lastname: Piazza
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Bruce
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Zoller
authors.forename: Brian
authors.initials: B
authors.lastname: Hwang
authors.forename: Aimee
authors.initials: A
authors.lastname: Monahan
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Hwang
authors.forename: Sergey
authors.initials: S
authors.lastname: Kisslev
authors.forename: Stephan
authors.initials: S
authors.lastname: Mayer
authors.forename: Philip M
authors.initials: PM
authors.lastname: Meyers
authors.forename: Neeraj
authors.initials: N
authors.lastname: Badjatia
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
mesh_terms: D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010974:Platelet Aggregation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020127:Recovery of Function / Q000235:genetics*
chemical_list: D058544:Class Ib Phosphatidylinositol 3-Kinase; C546760:PIK3CG protein, human