Design of a prospective neonatal cohort study of homozygous and double heterozygous Factor V Leiden and Factor II G20210A

Abstract.

Background: Factor V Leiden (FVL) and Factor II (FII) G20210A represent common risk factors for thromboembolic (TE) events. In children, both venous and arterial TE-events have been associated with the presence of FVL and FII G20210A. In most heterozygous children with TE-events other prothrombotic factors can usually be identified. Case reports of children with homozygous FVL, including 3 patients described here, suggest that this genotype may convey a particulary high risk. However, prospective data about the type and frequency of TE-events in such children are lacking. Study design: We have initiated a prospective neonatal cohort study for the homozygous and double heterozygous genotypes for FVL and FII G20210A. The probands and the heterozygous controls are identified by neonatal screening that involves > 98 % of the children born in Berlin and are followed up in a special out-patient clinic to document details of the clinical history, developmental parameters and the occurrence of TE-events. Conclusions: This study will provide controlled and unbiased information about the clinical significance of the homozygous and double heterozygous genotypes of these mutations.

Hintergrund: Die Faktor V Leiden (FVL) und die FII G20210A Mutationen stellen bekannte Risikofaktoren für thromboembolische (TE-) Ereignisse dar. Im Kindesalter sind sowohl venöse als auch arterielle TE-Ereignisse mit dem Vorkommen der FVL oder der FII G20210A Mutation assoziiert. Bei heterozygoten Kindern mit TE-Ereignissen können meist weitere prothrombotische Faktoren identifiziert werden. Mehrere Fallberichte lassen für Kinder mit homozygotem Genotyp für FVL ein höheres Risiko vermuten. Prospektive Daten über Häufigkeit und Typ von TE-Ereignissen bei solchen Kindern liegen jedoch bislang nicht vor. Studiendesign: Wir initiierten eine prospektive neonatale Kohortenstudie zum homozygoten und doppelt heterozygoten Genotyp für die FVL und die FII G20210A Mutationen. Die Probanden und die heterozygoten Kontrollen werden im Rahmen des neonatalen Screening identifiziert, welches > 98 % der Neugeborenen in Berlin umfasst. Die Follow-up-Untersuchungen beinhalten die Dokumentation der Anamnese, des entwicklungsneurologischen und allgemein-pädiatrischen Untersuchungsbefundes und des Auftretens von TE-Ereignissen. Schlussfolgerung: Diese Studie wird kontrollierte und prospektive Informationen zur klinischen Bedeutung des homozygoten und des doppelt heterozygoten Genotyps für diese Mutationen liefern.

Key words:

Thrombosis in children - Factor V Leiden - Factor II G20210A

Schlüsselwörter:

Thrombose bei Kindern - Faktor V Leiden - Faktor II G20210A

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