Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
J Cardiothorac Vasc Anesth. 2010 Jun;24(3):427-33. doi: 10.1053/j.jvca.2009.10.030. Epub 2010 Jan 6.
Hemorrhage continues to be a major problem after cardiac surgery despite the routine use of antifibrinolytic drugs, with striking inter-patient variability poorly explained by already known risk factors. The authors tested the hypothesis that genetic polymorphisms of inflammatory mediators and cellular adhesion molecules are associated with bleeding after cardiac surgery.
Prospective, observational study.
Single, tertiary referral university heart center.
Adult patients undergoing aortocoronary surgery with cardiopulmonary bypass.
Patients (n = 759) had 10 mL of blood drawn preoperatively and genomic DNA isolated then genotyped for 17 polymorphisms in 7 candidate genes: tumor necrosis factor, interleukins 1beta and 6, interleukin 1 receptor antagonist, intercellular adhesion molecule-1 (ICAM-1), P-selectin and endothelial leucocyte adhesion molecule-1 (E-selectin). Multivariate analyses were used to relate clinical and genetic factors to bleeding and transfusion.
The 98G/T polymorphism of the E-selectin gene was independently associated with bleeding after cardiac surgery (p = 0.002), after adjusting for significant clinical predictors (patient size and baseline hemoglobin concentration). There was a gene dose effect according to the number of minor alleles in the genotype; carriers of the minor allele bled 17% (GT) and 54% (TT) more than wild type (GG) genotypes, respectively (p = 0.01). Carriers of the minor allele also had longer activated partial thromboplastin times (p = 0.0023) and increased fresh frozen plasma transfusion (p = 0.03) compared with wild type.
The authors found a dose-related association between the 98T E-selectin polymorphism and bleeding after cardiac surgery, independent of and additive to standard clinical risk factors.
尽管常规使用抗纤维蛋白溶解药物，心脏手术后仍持续存在出血问题，且患者间的明显变异性无法用已确定的风险因素很好地解释。作者检验了这样一个假设，即炎症介质和细胞黏附分子的遗传多态性与心脏手术后出血有关。
前瞻性、观察性研究。
单中心、三级转诊大学心脏中心。
接受体外循环主动脉冠状动脉手术的成年患者。
患者（n = 759）术前抽取 10 毫升血，提取基因组 DNA，然后对 7 个候选基因的 17 个多态性进行基因分型：肿瘤坏死因子、白细胞介素 1β和 6、白细胞介素 1 受体拮抗剂、细胞间黏附分子-1（ICAM-1）、P 选择素和内皮白细胞黏附分子-1（E-选择素）。采用多元分析将临床和遗传因素与出血和输血相关联。
E-选择素基因的 98G/T 多态性与心脏手术后出血独立相关（p = 0.002），调整了显著的临床预测因素（患者体型和基线血红蛋白浓度）后仍然如此。根据基因型中的少数等位基因数量，存在基因剂量效应；与野生型（GG）基因型相比，少数等位基因携带者分别出血多 17%（GT）和 54%（TT）（p = 0.01）。少数等位基因携带者的活化部分凝血活酶时间也更长（p = 0.0023），且与野生型相比，新鲜冷冻血浆输注量更多（p = 0.03）。
作者发现 98T E-选择素多态性与心脏手术后出血之间存在剂量相关关系，这种关系独立于且附加于标准临床危险因素。
