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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
Verena Limperger
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
,
Andre Franke
2   Institute of Clinical Molecular Biology, Christian-Albrechts-Univ. of Kiel, Germany
,
Gili Kenet
3   Thrombosis Unit, National Hemophilia Center, Tel Hashomer and the Sackler Medical School, Tel Aviv University, Israel
,
Susanne Holzhauer
4   Department of Pediatric Hematology/Oncology, Charité, Berlin, Germany
,
Veronique Picard   *
5   AP-PH, Service d’Hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France
,
Ralf Junker
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
,
Christine Heller
6   Department of Pediatric Hemostaseology, Frankfurt, Germany
,
Christian Gille
7   Department of Neonatology, Univ. Children Hospital Tübingen, Germany
,
Daniela Manner
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
8   Department of Pediatric Hematology /Oncology, Münster, Germany
,
Karin Kurnik
9   Department of Pediatrics, Univ. Children Hospital Munich, Germany
,
Ralf Knoefler
10   Department of Pediatric Hemostaseology, Dresden, Germany
,
Rolf Mesters
11   Department of Medicine/ Hematology & Oncology, Univ. Hospital of Münster, Germany
,
Susan Halimeh
12   Coagulation Center Rhine-Ruhr, Duisburg, Germany
,
Ulrike Nowak-Göttl
8   Department of Pediatric Hematology /Oncology, Münster, Germany
13   Center of Thrombosis and Hemostasis, Department of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
› Author Affiliations
Further Information

Publication History

Received: 18 February 2014

Accepted after major revision: 02 April 2014

Publication Date:
02 December 2017 (online)

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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

* Present adress: Laboratoire d’Hématologie, AP-HP, CHU Bicêtre, Université Paris Sud, Le Kremlin-Bicêtre, France.


 

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