Influence of PAI-1 Gene Promoter-675 (4G/5G) Polymorphism on Fibrinolytic Activity After Cardiac Surgery Employing Cardiopulmonary Bypass

Abstract

Background and Objective. The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery.Material and Methods. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/ PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery.Results. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups.Conclusions. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

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

“…The promoter regions 675 4Guanine/5Guanine (4G/5G) and −844 Adenosine/Guanine (A/G) polymorphisms, both affecting the fibrinolytic balance, are two of the most common. 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 – 14 ].…”

“…Postoperative bleeding volumes were recorded as chest tube drainage (CTD) in mL at 4 and 24 h after the surgery [ 9 ]. Inclusion and exclusion criteria, as well as perioperative management, postoperative bleeding and demographic and laboratory data were the same as published before [ 9 ] and genomic DNA was extracted as reported by Ozolina et al [ 14 ]. Here, we only describe the methods used for analysis of PAI-1 -844 A/G and ACE Intron 16 I/D polymorphisms.…”

“…However, the ACE Intron 16 I/D polymorphism has been sparsely studied, as a potential cause of postoperative bleeding, and with controversial results [ 25 , 29 , 30 ]. Consequently, by examining the same patient cohort as referred to above [ 14 ], our primary end-point was to address the associations between PAI-1 -844 A/G and ACE Intron 16 I/D polymorphisms and fibrinolytic bleeding after cardiac surgery using CPB.…”