Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery.

Agnese Ozolina,Lars J Bjertnaes,Indulis Vanags,Angelika Krumina,Liene Nikitina-Zake,Eva Strike,Romans Lacis,Inta Jaunalksne

doi:10.1186/s12871-015-0101-1

Abstract

BackgroundCarriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding.MethodsWe assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation.ResultsThe lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G.ConclusionsIncreased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-015-0101-1) contains supplementary material, which is available to authorized users.

Highlights

Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB)
Clinical course Out of totally, 90 consecutive patients scheduled for first time cardiac surgery, 83 patients, 42 men and 41 women, who met inclusion criteria were subjected to further analysis (Table 1)
Patients were classified with their PAI-1-844 A/G and angiotensin converting enzyme (ACE) Intron 16 I/D characteristics and subdivided into 3 groups, according to the genotype of each polymorphism

Summary

Introduction

Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). Heart surgery by means of cardiopulmonary bypass (CPB) can impede hemostasis, thereby increasing postoperative bleeding and the need for blood transfusions [1, 2]. In a previous study of patients, who underwent cardiac surgery on CPB, we found that lower plasma concentrations of PAI-1 preoperatively were associated with more. Reassessing blood from the latter study [9], we recently confirmed the findings of other investigators that in addition to decreased plasma levels of PAI-1, excessive bleeding after CPB was associated with PAI-1 -675 5G/5G polymorphism [5, 10,11,12,13,14]

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