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

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.

Meta-analysis of the Sources of Bleeding after Adult Cardiac Surgery

“…Eighteen studies including 2455 patients 5,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] fulfilled the pre-specified selection criteria and were included in this analysis ( Fig. 1).…”

Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

“…There also may be a genetic predisposition to developing each of these phenotypes. Polymorphisms of the PAI-1 gene have been associated with bleeding complications during cardiac surgery(47) and thrombotic complications predicting poor outcomes after myocardial infarct(48). We also appreciated an increase in age was associated with an increase in the fibrinolysis shutdown phenotype.…”

The Synergistic Effect of Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphisms and Metabolic Syndrome on Coronary Artery Disease in the Korean Population

“…The −675 4G > 5G polymorphism (rs1799762), located in the PAI-1 promotor region, is also reported to be associated with various atherosclerotic diseases including venous thromboembolism [ 20 ], ischemic stroke [ 21 ], carotid artery stenosis [ 22 ], renal artery stenosis [ 23 ], and coronary artery disease [ 24 ]. Moreover, these three polymorphisms are reported to be associated with plasma PAI-1 levels [ 25 , 26 ]. Therefore, we designed a genetic epidemiological study of the three most extensively studied polymorphisms of PAI-1 to investigate the association between PAI-1 and CAD in Korean populations.…”