Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-24T13:49:18.687Z Has data issue: false hasContentIssue false
  • English
  • Français

Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery

Published online by Cambridge University Press:  14 April 2005

Namık Özbek ,
F. Belgin Ataç ,
Selman V. Yıldırim ,
Hasibe Verdi ,
Canan Yazıcı ,
Başak T. Yılmaz  and
N. Kürşat Tokel
Namık Özbek
Affiliation:
Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara, Turkey
F. Belgin Ataç
Affiliation:
Department of Molecular Biology and Genetics, Başkent University, Faculty of Medicine, Ankara, Turkey
Selman V. Yıldırim
Affiliation:
Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara, Turkey
Hasibe Verdi
Affiliation:
Department of Molecular Biology and Genetics, Başkent University, Faculty of Medicine, Ankara, Turkey
Canan Yazıcı
Affiliation:
Department of Medical Statistics, Başkent University, Faculty of Medicine, Ankara, Turkey
Başak T. Yılmaz
Affiliation:
Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara, Turkey
N. Kürşat Tokel
Affiliation:
Department of Pediatrics, Başkent University, Faculty of Medicine, Ankara, Turkey
Get access Rights & Permissions [Opens in a new window]

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.1 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.

Keywords

Postoperative carechildrencongenital heart malformationspoint mutations
Type
Original Article
Information
Cardiology in the Young , Volume 15 , Issue 1 , January 2005 , pp. 19 - 25
Copyright
2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Goldmuntz E. The epidemiology and genetics of congenital heart disease. Clin Perinatol 2001; 28: 1–10.Google Scholar
De Stefano V, Zappacosta B, Persichilli S, et al. Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (Factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease. Br J Haematol 1999; 106: 564–568.Google Scholar
Akar N, Akar E, Akçay R, Avcu F, Yalçin A, Cin S. Effect of methylenetetrahydrofolate reductase 677 C-T, 1298 A-C, and 1317 T-C on factor V 1691 mutation in Turkish deep vein thrombosis patients. Thromb Res 2000; 97: 163–167.Google Scholar
Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P. Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int 2001; 60: 46–54.Google Scholar
Balogh I, Szoke G, Karpati L, et al. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479–2486.Google Scholar
Carter AM, Catto AJ, Grant PJ. Association of the alpha-fibrinogen Thr312Ala polymorphism with poststroke mortality in subjects with atrial fibrillation. Circulation 1999; 99: 2423–2426.Google Scholar
Yoon Y, Song J, Hong SH, Kim JQ. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem 2000; 46: 1626–1630.Google Scholar
Gürgey A, Mesci L. The prevalence of Factor V Leiden (1691 G → A) mutation in Turkey. Turk J Pediatr 1997; 39: 313–315.Google Scholar
Akar N, Mısırlıoğlu M, Akar E, Avcu F, Yalçın A, Sözuöz A. Prothrombin gene 20210 G-A mutation in the Turkish population. Am J Hematol 1998; 58: 249.Google Scholar
Ermis C, Tsai MY, Hanson NQ, Akar N, Aras O. Angiotensin I converting enzyme, angiotensin II type 1 receptor and angiotensinogen polymorphisms and early myocardial infarction in the Turkish population. Thromb Haemost 2002; 88: 693–694.Google Scholar
Gürgey A, Özyürek E, Gümrük F, et al. Thrombosis in children with cardiac pathology: frequency of Factor V Leiden and prothrombin G20210A mutations. Pediatr Cardiol 2003; 24; 244–248.Google Scholar
Jackson A, Brown K, Langdown J, Luddington R, Baglin T. Effect of angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism. Br J Haematol 2000; 111: 562–564.Google Scholar
Lamas S, Marsden PA, Li GK, Tempst P, Michel T. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci USA 1992; 89: 6348–6352.Google Scholar
Song J, Yoon Y, Park KU, et al. Genotype-specific influence on nitric oxide synthase gene expression, protein concentrations, and enzyme activity in cultured human endothelial cells. Clin Chem 2003; 49: 847–852.Google Scholar
Hooper WC, Lally C, Austin H, et al. The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans. Chest 1999; 116: 880–886.Google Scholar
Duncan JA, Scholey JW, Miller JA. Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes. Curr Opin Nephrol Hypertens 2001; 10: 111–116.Google Scholar