Appelboom Geoffrey, Piazza Matthew, Bruce Samuel S, Zoller Stephen D, Hwang Brian, Monahan Aimee, Hwang Richard Y, Kisslev Sergey, Mayer Stephan, Meyers Philip M, Badjatia Neeraj, Connolly E Sander
Cerebrovascular Laboratory Columbia University, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Neurol Res. 2012 Apr;34(3):232-7. doi: 10.1179/1743132811Y.0000000080. Epub 2012 Mar 1.
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.
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.
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.
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.
血小板聚集的改变已被证明会促进脑出血（ICH）后的出血并影响预后。我们研究了血小板聚集基因变异的影响及其对入院时脑出血体积和临床结局的作用。
我们的前瞻性研究分析了先前全基因组关联研究中与血小板聚集表型相关的选定候选单核苷酸多态性（SNP），涉及结局和脑出血体积。患者在哥伦比亚大学医学中心神经重症监护病房接受评估。排除标准包括年龄<18岁、创伤后脑出血、出血性转化或肿瘤、不同意进行基因分析或数据不完整。前瞻性记录放射学变量（急性脑出血的位置和体积、脑室内扩展的存在、中线移位和脑积水）和临床变量（出院时的死亡率和改良Rankin评分）。
纳入了2009年2月至2011年5月间通过临床评估和入院计算机断层扫描诊断的122例自发性脑出血患者。入院时格拉斯哥昏迷量表评分（GCS）中位数为11.5。出院时死亡率的单因素预测因素包括收缩压、脑室内出血的存在、抗凝剂的使用和GCS，唯一的出院死亡率独立预测因素（P<0.001）。年龄、脑室内出血和GCS与功能结局不良相关；年龄（P = 0.001）和GCS（P<0.001）在多因素模型中具有显著意义。入院时GCS（P<0.01）、抗血小板药物的使用和rs342286（PIK3CG；P = 0.04；R(2)=0.247）与血肿体积存在单因素关联。
我们确定SNP rs342286是入院时血肿体积的独立预测因素。我们的研究结果表明，先前与该SNP相关并影响血小板聚集的PIK3CG功能会影响脑实质内出血的严重程度。
