Abstract

Chronic heart failure (CHF) is one of the most severe and adverse diseases of the cardiovascular system, which requires heart transplantation (HT) for patient. Implantation of the left ventricular assist device (LVAD) is the treatment option instead of HT. LVAD can be implanted as a bridge to transplantation and destination therapy (DT). Unfortunately, DT of the LVAD has side effects such as bleeding and thrombosis. These side effects occur because of the non-physiological high shear stress of the LVAD, which causes platelet degradation. However, side effects might occur because of the genetic polymorphisms in coagulation factors, platelet receptors etc. The purpose of the study is to identify the influence of the coagulation factor F5, F7 and FGB polymorphisms in LVAD patients. Venous blood samples were recruited from 100 patients with implanted LVAD at the National Research Center for Cardiac Surgery. Patients were prescribed with the dose of the warfarin according to the clinical protocol. Patients were divided into two groups: 1.Case study - patients with side effects; 2. Control study - patients without side effects. Genomic DNA was extracted by using the PureLink™ Genomic DNA Mini Kit (Invitrogen, UK). Genotyping of polymorphisms F5 (rs6025), F7 (rs6046) and FGB (rs1800790) was done by real-time polymerase chain reaction with TaqMan probes. Genotyping results of Factor Leiden V (F5) showed that most of the patients (99%) has wild type of genotype (C/C) which has no risk to thrombosis. On other hand, genotyping results of F7 and fibrinogen beta (FGB) polymorphisms presented different percentage results from F5. Results of polymorphism F7 showed wild type of genotype G/G in 76% patients, whereas only 3% patients has mutant genotype A/A which has no risk to thrombosis. Mutant genotype A/A of FGB polymorphism was expressed only in 3% of patients, which has high risk to thrombosis. Mutant version of polymorphisms shows that some LVAD patients have high risk to side effects apart from high shear stress. The study has presented that side effects might happen because of the individual genome differences in LVAD patients. Some patients demonstrated high risk of side effects on destination therapy as well as according to genotyping results too.

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