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


METHODS
We 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.


RESULTS
The 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.


CONCLUSIONS
Increased 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.
Department of Cardiac surgery, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, Latvia. agnese_krauze@yahoo.com.|Riga Stradins University, Dzirciema Street 16, Riga, Latvia. agnese_krauze@yahoo.com.
Agnese
A
Ozolina
Department of Cardiac surgery, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, Latvia. evastrike@gmail.com.|Riga Stradins University, Dzirciema Street 16, Riga, Latvia. evastrike@gmail.com.
Eva
E
Strike
Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga, Latvia. lienik@biomed.lu.lv.
Liene
L
Nikitina-Zake
Clinical Immunology Centre, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, Latvia. inta.jaunalksne@stradini.lv.
Inta
I
Jaunalksne
Department of Infectology and Dermatology, Riga Stradins University, Dzirciema Street 16, Riga, Latvia. angelika@covalent.lv.
Angelika
A
Krumina
Department of Cardiac surgery, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, Latvia. valentina@stradini.lv.|Riga Stradins University, Dzirciema Street 16, Riga, Latvia. valentina@stradini.lv.
Romans
R
Lacis
Anesthesia and Critical Care Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway. lars.bjertnaes@uit.no.
Lars J
LJ
Bjertnaes
Riga Stradins University, Dzirciema Street 16, Riga, Latvia. indulis.vanags@stradini.lv.
Indulis
I
Vanags
D000368:Aged; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D007703:Peptidyl-Dipeptidase A