title: Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery.
abstract: In this study, we investigated some of the prothrombothic mutations and polymorphisms in 15 children with congenital cardiac malformations who developed severe thrombosis in the perioperative period following surgical repair. The mutations and polymorphisms included in the study were Factor V Leiden, prothrombin G20210A, methylentetrahydrofolate reductase C677T, endothelial nitric oxide synthase intron 4 VNTR, alpha-fibrinogen Thr312Ala, Factor XIII Val34Leu, and insertion or deletion of angiotensin 1 converting enzyme. Compared to the healthy Turkish subjects, our patients had a similar rate of mutation of Factor V Leiden, Factor XIII Val34Leu, and endothelial nitric oxide synthase a/b polymorphisms, but higher frequency of the prothrombotic angiotensin 1 converting enzyme deletion/deletion genotype, and lower frequency of the antithrombotic alpha fibrinogen Thr/Thr genotype. None of the patients exhibited mutations involving prothrombin G20210A or methylentetrahydrofolate reductase C677T. The results of our study suggest that, in addition to prothrombotic mutations such as Factor V Leiden, single-nucleotide polymorphisms should be considered in all children with congenital cardiac malformations who develop thrombosis. Malformations of the heart are the most common of all serious lesions that are present at birth, with an incidence of 4 to 8 cases per 1,000 live births. If needed, corrective surgery is usually the optimal treatment for these anomalies, but perioperative morbidity and mortality still remain high due to several factors. Arterial or venous thrombosis, or both varieties of thrombosis, is among these factors. Prior to surgery, the most frequent time at which these children develop thrombosis is during cardiac catheterization. Postoperative thrombosis in this group of patients is a more complex disorder, which can affect both small and large vessels, and is associated with a high morbidity and mortality. Recent studies indicate that both point mutations and single-nucleotide polymorphisms of genes that encode proteins involved in the coagulative and anticoagulative cascades are important risk factors for development of thrombosis. Patients with these risk factors are most likely to develop thrombosis when triggering elements, such as placement of catheters, prolonged immobilization, or surgery, are also present. In this study, we investigated some of the above-mentioned mutations and polymorphisms in children who developed thrombosis in the perioperative period after correction of congenital cardiac malformations.
authors.affiliation: Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara, Turkey. nozbek@tr.net
authors.forename: Namik
authors.initials: N
authors.lastname: Ozbek
authors.forename: F Belgin
authors.initials: FB
authors.lastname: Ataç
authors.forename: Selman V
authors.initials: SV
authors.lastname: Yildirim
authors.forename: Hasibe
authors.initials: H
authors.lastname: Verdi
authors.forename: Canan
authors.initials: C
authors.lastname: Yazici
authors.forename: Başak T
authors.initials: BT
authors.lastname: Yilmaz
authors.forename: N Kürşat
authors.initials: NK
authors.lastname: Tokel
mesh_terms: D002675:Child, Preschool; D005165:Factor V / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006344:Heart Septal Defects, Atrial / Q000601:surgery; D006345:Heart Septal Defects, Ventricular / Q000601:surgery; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000503:physiopathology*; D011516:Prothrombin / Q000235:genetics; D013927:Thrombosis / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D005176:Factor XIII; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A