844 A/G Polymorphism Of PAI-1 Gene In Association With Fibrinolytic Bleeding After Cardiac Surgery Employing CPB

Background and objective:The application of Cardiopulmonary bypass(CPB)solves the problem of oxygenation of patients who under cardiac valve surgery,however,CPB causes coagulation dysfunction and hyperfibrinolysis,which lead to excessive postoperative bleeding.Postoperative bleeding is still a serious problem in cardiac surgery.It is an important factor for perioperative blood transfusion,reoperation which increases the mortality of the patients.It has been reported that low-risk cardiac surgery requires a higher transfusion rate,but the use of blood products causes a series of complications.Therefore,it is very important to find out the causes of abnormal bleeding after CPB in order to implement intervention measures.A study reported that more than half of the patients undergoing reoperation had no obvious bleeding spots,which suggests that abnormal bleeding is associated with coagulopathy and/or hyperfibrinolysis.Increasing platelet destruction,the depletion of massive coagulation factors which results in coagulation dysfunction,and combining with the higher fibrinolytic activity,the balance of coagulation and fibrinolytic system is no longer exist.As the most important inhibitor of the fibrinolytic system,Plasminogen activator inhibitor-1(PAI-1)helps to maintain the balance of coagulation and fibrinolytic system.Plasma PAI-1 levels and activity are regulated by PAI-1 gene polymorphisms.At present,it has been found that a few sites with single nucleotide polymorphisms(SNPs)have a significant relationship with plasma PAI-1 concentration or activity.Among them,the gene polymorphism of-844A/G is caused by a single base substitution.It belongs to a restriction fragment of DNA,which can be bound in ETS(E-twenty six)protein(a transcription factor)specifically.And it can influence the transcriptional activity and thus the expression of PAI-1 protein.It can affect transcriptional activity of PAI-1 gene,thereby affecting PAI-1 expression.G allele has the lowest transcriptional activity,and lowest PAI plasma concentration,which increases bleeding tendency.Abnormal bleeding after cardiac surgery is often associated with coagulopathy and hyperfibrinolysis.PAI-1 is a major inhibitor of the fibrinolytic system,patients with PAI-1 deficiency are often present with postoperative and post-traumatic abnormal bleeding.This study explored the relationship between PAI-1-844 A / G polymorphism and abnormal bleeding after cardiac surgery under CPB.MethodsA total of 90 adult patients scheduled for cardiac surgery employing CPB from January 2017 to January 2018 in the First Affiliated Hospital of Zhengzhou University were enrolled into our study.Inclusion criteria included: > 18 years of age,first-time cardiac surgery under CPB,coagulation tests within normal ranges at baseline: prothrombin time(70%-120%)or international normalized ratio 0.8-1.2,anti-aggregating or no anticoagulant,non-steroidal anti-inflammatory drugs for,at least,one week prior to surgery in order to disclose drug-induced platelet dysfunction.The following conditions need to be excluded: platelet dysfunction,history of coagulopathy and/or bleeding disorders,severe renal and/or liver dysfunction,redo surgeryand emergency surgery.After entering the operating room,we checked the patient,and performed electrocardiographic monitoring on the patient,and then opened the peripheral venous access.The patient was inhaled with oxygen in order to depriving of nitrogen.The patients were induced by rapid intravenous anesthesia.A video laryngoscope is used for tracheal intubation.intravenously maintained with inhalation of sevoflurane to maintain anesthesia.The patient returned to the intensive care unit with the trachea incubated after surgery.Blood samples were collected from every selected patients at 8:00 a.m of the day before surgery to detect genotypes,the plasma concentrations of PAI-1 as well as blood routine and hemagglutination tests.The patients were allocated to 3 groups: A/A group,A/G group and G/G group depending on the results of genotype detection.Blood samples were collected to detect the plasma concentrations of D-dimer and the volume of mediastina pericardial drainage,once the patients arrived at ICU(T1),four hours(T2)and twenty-four hours hours(T3)after surgery.The plasma concentrations of t-PA/PAI-1 complex and the Chest drainage were detected twenty-four hours after the surgery.We also recorded the volume of prime solution,the surgery time,CPB time,aortic clamping time and so on.Statistical analysisThe collected data were analyzed with SPSS 21.0.Categorical variables are expressed as a percentage(%).The data of the study groups were checked by an appropriate analytic test according to the data distribution.The numerical data conformed to normal distribution were expressed as mean±standard deviation.ANOVA for parametric variables,Chi-square test was used to analyze categorical data.Statistical significance was defined as P?0.05.Results1.Finally 90 patients scheduled for cardiac surgery,were enrolled into the study.There were 24 in the A/A group,46 in the A/G group,and 20 in the G/G group.2.Plasma concentration of PAI-1 preoperatively decreased gradually in A/A group,A/G group and G/G group one by one,and there was a significant difference between A/A group and G/G group(P < 0.05).3.The chest drainage volume in the G/G group was the highest at 4 hours postoperatively,and there was a significant difference between A/A group and A/G group(P < 0.05).4.The plasma of t-PA/PAI-1 was the lowest in the G/G group 24 hours after the operation,but there was no significant difference among the three groups.(P > 0.05).5.Compared with the A/A group,the plasma concentration of D-dimer in the G/G group was significantly higher at 4 hours and 24 hours postoperatively(P < 0.05).Conclusion1.Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with the-844A/G polymorphism of PAI-1 gene.2.The-844A/G polymorphism of PAI-1 gene affects the plasma PAI-1 concentration.G/G homozygous has a lower plasma PAI-1 level,which increases fibrinolytic activity and leads to increased postoperative blood loss after cardiac surgery using cardiopulmonary bypass.