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




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BMC Anesthesiology

, 15:122

First Online: 04 September 2015Received: 03 September 2014Accepted: 26 August 2015

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.

AbbreviationsACE 16 intron I-DAngiotensin converting enzyme insertion-deletion gene polymorphism at 16-intron rs4646994

ACTActivated coagulation time

BMIBody mass index

CABGCoronary artery bypass grafting

CPBCardiopulmonary bypass

CTDChest tube drainage

EuroSCOREEuropean system for cardiac operative risk evaluation

HbHemoglobin

ICUIntensive care unit

kgKilograms

LMWHLow molecular weight heparin

PAI-1Plasminogen activator inhibitor type-1

PAI-1-675 4G5GPlasminogen activator inhibitor −1 gene 4 Guanine-5Guanine polymorphism at position 675 rs1799768

PAI-1-844 A-GPlasminogen activator inhibitor type-1 Adenosine-Guanine polymorphism at position 844 rs2227631

PCRPolymerase chain reaction

PLTPlatelets

RAASRenin angiotensin aldosteron system

SDStandard deviation

sSeconds

TEG-ROTEMThromboelastography-thromboelastometry

t-PATissue plasminogen activator

t-PA-PAI-1Complex of tissue plasminogen activator and plasminogen activator inhibitor type-1

0 hTime point immediately after surgery

4 hTime point 4 h after surgery

6 hTime point 6 h after surgery

24 hTime point 24 h after surgery

Agnese Ozolina, Liene Nikitina-Zake and Inta Jaunalksne contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12871-015-0101-1 contains supplementary material, which is available to authorized users.

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Autor: Agnese Ozolina - Eva Strike - Liene Nikitina-Zake - Inta Jaunalksne - Angelika Krumina - Romans Lacis - Lars J. Bjertnaes

Fuente: https://link.springer.com/



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