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; R2 = 0·247) had univariate associations with hematoma volume.Discussion: 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.