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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
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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

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