Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency

Verena Limperger; Andre Franke; Gili Kenet; Susanne Holzhauer; Veronique Picard; Ralf Junker; Christine Heller; Christian Gille; Daniela Manner; Karin Kurnik; Ralf Knoefler; Rolf Mesters; Susan Halimeh; Ulrike Nowak-Göttl

doi:10.1160/TH14-02-0149

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(03): 478-485
DOI: 10.1160/TH14-02-0149

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency

An observational multicentre cohort study

Authors

Verena Limperger

¹Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
Andre Franke

²Institute of Clinical Molecular Biology, Christian-Albrechts-Univ. of Kiel, Germany
Gili Kenet

³Thrombosis Unit, National Hemophilia Center, Tel Hashomer and the Sackler Medical School, Tel Aviv University, Israel
Susanne Holzhauer

⁴Department of Pediatric Hematology/Oncology, Charité, Berlin, Germany
Veronique Picard^*

⁵AP-PH, Service d’Hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France
Ralf Junker

¹Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
Christine Heller

⁶Department of Pediatric Hemostaseology, Frankfurt, Germany
Christian Gille

⁷Department of Neonatology, Univ. Children Hospital Tübingen, Germany
Daniela Manner

¹Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany

⁸Department of Pediatric Hematology /Oncology, Münster, Germany
Karin Kurnik

⁹Department of Pediatrics, Univ. Children Hospital Munich, Germany
Ralf Knoefler

¹⁰Department of Pediatric Hemostaseology, Dresden, Germany
Rolf Mesters

¹¹Department of Medicine/ Hematology & Oncology, Univ. Hospital of Münster, Germany
Susan Halimeh

¹²Coagulation Center Rhine-Ruhr, Duisburg, Germany
Ulrike Nowak-Göttl

⁸Department of Pediatric Hematology /Oncology, Münster, Germany

¹³Center of Thrombosis and Hemostasis, Department of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany

Abstract

Summary

Venous thromboembolism [TE] is a multifactorial disease and antithrombin deficiency [ATD] constitutes a major risk factor. In the present study the prevalence of ATD and the clinical presentation at TE onset in a cohort of paediatric index cases are reported. In 319 un - selected paediatric patients (0.1–18 years) from 313 families, recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. 21 of 319 paediatric patients (6.6%), corresponding to 16 of 313 families (5.1%), were AT-deficient with confirmed underlying AT gene mutations. Mean age at first TE onset was 14 years (range 0.1 to 17). Thrombotic locations were renal veins (n=2), cerebral veins (n=5), deep veins (DVT) of the leg (n=9), DVT & pulmonary embolism (n=4) and pelvic veins (n=1). ATD co-occurred with the factor- V-Leiden mutation in one and the prothrombin G20210A mutation in two children. In 57.2% of patients a concomitant risk factor for TE was identified, whereas 42.8% of patients developed TE spontaneously. A second TE event within primarily healthy siblings occurred in three of 313 families and a third event among siblings was observed in one family. In an unselected cohort of paediatric patients with symptomatic TE, the prevalence of ATD adjusted for family status was 5.1%. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high risk population.

Keywords

Antithrombin deficiency - genetics - children

Full Text

References

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