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Thromb Haemost 2015; 113(02): 426-433
DOI: 10.1160/TH14-06-0533
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Role of protein S deficiency in children with venous thromboembolism

An observational international cohort study
Ulrich C. Klostermeier   *
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
,
Verena Limperger   *
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
,
Gili Kenet
2   Thrombosis Unit, National Hemophilia Center, Tel Hashomer and the Sackler Medical School, Tel Aviv University, Israel
,
Karin Kurnik
3   Department of Pediatrics, Univ. Children Hospital Munich, Germany
,
Martine Alhenc Gelas
4   Service d’hématologie biologique, AP-HP, Hôpital Europeen Georges Pompidou, Paris, France
,
Ulrich Finckh
5   Medizinisches Versorgungszentrum Eberhard & Partner, Dortmund, Germany
,
Ralf Junker
1   Institute of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
,
Christine Heller
6   Department of Pediatric Hemostaseology, Frankfurt, Germany
,
Barbara Zieger
7   Department Pediatrics, Univ. Children Hospital Freiburg, Germany
,
Ralf Knöfler
8   Department of Pediatric Hemostaseology, Dresden, Germany
,
Susanne Holzhauer
9   Department of Pediatric Hematology/Oncology, Charité, Berlin, Germany
,
Rolf Mesters
10   Department of Medicine/ Hematology & Oncology, Univ. Hospital of Münster, Germany
,
Anne Krümpel
11   Univ. Children Hospital, Münster, Germany
,
Ulrike Nowak-Göttl
11   Univ. Children Hospital, Münster, Germany
12   Center of Thrombosis and Hemostasis, Department of Clinical Chemistry, Univ. Hospital of Kiel & Lübeck, Germany
› Author Affiliations
Further Information

Publication History

Received: 19 June 2014

Accepted after major revision: 28 August 2014

Publication Date:
27 November 2017 (online)

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Summary

Venous thromboembolism [TE] is a multifactorial disease, and protein S deficiency [PSD] constitutes a major risk factor. In the present study the prevalence of PSD and the clinical presentation at TE onset in a cohort of children is reported. In 367 unselected paediatric patients with TE (age 0.1–18 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Thirty of 367 paediatric patients (8.2 %) derived from 27 families had PSD. Mean age at first TE onset was 14.5 years (range 0.1 to 18). Thrombotic locations were cerebral veins (n=8), calf vein TE (n=3) deep veins (DVT) of the leg (n=12), DVT & pulmonary embolism (n=5) and intra-cardiac veins (n=1) or purpura fulminans (n=1). PSD co-occurred with the factor 5 mutation at rs6025 or the homozygous factor 2 susceptibility variant at rs1799963 in one case each. The Heerlen polymorphism detected in five children presented with milder PSD. In 18 patients (60 %) a concomitant risk factor for TE was identified. A second TE event within primarily healthy siblings occurred in three of 27 PSD families (11.0 %). In this cohort of children with symptomatic TE, the prevalence of PSD adjusted for family status was 7.4 %. 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

Protein S deficiency - genetics - children

* UCK and VL contributed equally to this paper.


 

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