Greiff G, Pleym H, Stenseth R, Wahba A, Videm V
Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Cardiothoracic Anaesthesia and Intensive Care, St. Olavs University Hospital, Trondheim, Norway.
Acta Anaesthesiol Scand. 2015 Jul;59(6):796-806. doi: 10.1111/aas.12504. Epub 2015 Mar 12.
Severe post-operative bleeding in cardiac surgery is associated with increased morbidity and mortality. We hypothesized that variation in genetic susceptibility contributes to post-operative bleeding in addition to clinical factors.
We included 1036 adults undergoing cardiac surgery with cardiopulmonary bypass. Two different endpoints for excessive post-operative bleeding were used, either defined as blood loss exceeding 2 ml/kg/h the first 4 h post-operatively or a composite including bleeding, transfusions, and reoperations. Twenty-two single nucleotide polymorphisms (SNPs) central in the coagulation and fibrinolysis systems or in platelet membrane receptors were genotyped, focusing on replication of earlier non-replicated findings and exploration of potential novel associations. Using logistic regression, significant SNPs were added to a model with only clinical variables to evaluate whether the genetic variables provided additional information.
Univariate tests identified rs1799809 (located in the promoter region of the PROC gene), rs27646 and rs1062535 (in the ITGA2 gene), rs630014 (in the ABO gene), and rs6048 (in the F9 gene) as significantly associated with excessive post-operative bleeding (P < 0.05, P-values confirmed by permutation). The SNPs were significant also after adjustment with clinical variables, showing almost unchanged odds ratios except for rs1799809 (P = 0.06). Addition of the genetic covariates to a logistic regression model with clinical variables significantly improved the model (P < 0.01).
We identified five SNPs associated with post-operative bleeding after cardiac surgery, of which two validated previously published associations. Addition of genetic information to models with only clinical variables improved the models. Our results indicate that common genetic variations significantly influence post-operative bleeding after cardiac surgery.
心脏手术术后严重出血与发病率和死亡率增加相关。我们推测，除临床因素外，遗传易感性的差异也会导致术后出血。
我们纳入了1036例接受体外循环心脏手术的成年人。使用了两种不同的术后出血过多的终点定义，一种定义为术后前4小时失血超过2毫升/千克/小时，另一种是包括出血、输血和再次手术的综合指标。对凝血和纤维蛋白溶解系统或血小板膜受体中的22个单核苷酸多态性（SNP）进行基因分型，重点是重复早期未重复的发现并探索潜在的新关联。使用逻辑回归，将显著的SNP添加到仅包含临床变量的模型中，以评估遗传变量是否提供了额外信息。
单变量检验确定rs1799809（位于PROC基因的启动子区域）、rs27646和rs1062535（位于ITGA2基因）、rs630014（位于ABO基因）和rs6048（位于F9基因）与术后出血过多显著相关（P < 0.05，通过置换确认P值）。在用临床变量调整后，这些SNP仍然显著，除rs1799809外，优势比几乎不变（P = 0.06）。将遗传协变量添加到包含临床变量的逻辑回归模型中显著改善了模型（P < 0.01）。
我们确定了五个与心脏手术后出血相关的SNP，其中两个验证了先前发表的关联。在仅包含临床变量的模型中添加遗传信息改善了模型。我们的结果表明，常见的基因变异显著影响心脏手术后的出血情况。
