Abstract
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. 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. 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. 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.
Highlights
Alterations in hemostasis during and after cardiac surgery may have a diversity of etiologies including surgery per se as well as effects of the cardiopulmonary bypass (CPB) on the coagulation and the inflammation cascades, and their cross-reactions with the fibrinolytic and the kinin-kallikrein systems [1, 2]
The carriers of the 5G/5G genotype showed the lower preoperative plasminogen activator inhibitor type-1 (PAI-1) levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis
As shown in Table, 83 patients were subject to the further analysis and were classified into 3 groups according to the PAI-1 genotype: 4G/4G group (n=21), 4G/5G group (n=42), and 5G/5G group (n=20)
Summary
Alterations in hemostasis during and after cardiac surgery may have a diversity of etiologies including surgery per se as well as effects of the cardiopulmonary bypass (CPB) on the coagulation and the inflammation cascades, and their cross-reactions with the fibrinolytic and the kinin-kallikrein systems [1, 2]. The balance among bleeding, normal hemostasis, and thrombosis is markedly influenced by the aggregation of functioning platelets, the rate of thrombin formation [3], and the fibrinolytic system, which plays a determinant role in this process [4, 5]. The effects of the fibrinolytic system are mediated by the activation of plasminogen to fibrin-degrading protease plasmin, which lyses fibrin. Fibrinolytic activity depends on the balance between. The active form is synthesized in platelets as well as in endothelium and adipose tissues. The formation of t-PA/PAI-1 complexes depends on the function and plasma concentrations of the 2 proteins: the greater t-PA and PAI-1 concentrations are, the higher concentration of the complex will appear in the circulation [12]
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