Total tissue factor pathway inhibitor is an independent risk factor for symptomatic paediatric venous thromboembolism and stroke

Christine Duering; Andrea Kosch; Claus Langer; Sabine Thedieck; Ulrike Nowak-Göttl

doi:10.1160/TH04-05-0293

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 707-712
DOI: 10.1160/TH04-05-0293

Theme Issue Article

Schattauer GmbH

Total tissue factor pathway inhibitor is an independent risk factor for symptomatic paediatric venous thromboembolism and stroke

Christine Duering

¹Department of Paediatric Haematology and Oncology, University of Münster, Germany

,

Andrea Kosch

¹Department of Paediatric Haematology and Oncology, University of Münster, Germany

,

Claus Langer

²Institute of Clinical Chemistry and Institute of Arteriosclerosis Research, University of Münster, Germany

,

Sabine Thedieck

¹Department of Paediatric Haematology and Oncology, University of Münster, Germany

,

Ulrike Nowak-Göttl

¹Department of Paediatric Haematology and Oncology, University of Münster, Germany

› Author Affiliations

Abstract

Summary

Tissue factor pathway inhibitor (TFPI) plays an important role in inhibiting tissue factor-induced coagulation by a factor Xadependent pathway of the activated tissue-factor VIIa complex. Decreased values of the latter inhibitor have been recently reported in adult patients with venous thrombosis (VT) or ischaemic stroke (IS). The present case-control study was therefore performed to evaluate whether a decreased TFPI concentration is also involved in paediatric symptomatic thromboembolism (ST). Total TFPI concentrations were measured along with established prothrombotic risk factors six to twelve months after the acute thrombotic onset in 144 Caucasian children aged 0.6 to 18 years (VT: n=80; IS: n=64). The cut-off values defined as age-dependent 10^th percentiles were obtained from 244 healthy controls. Median (range) values of TFPI were significantly lower in patients compared with control subjects [50.0(20.0-132.3) ng/ml vs. 59.5(25.4-117.4) ng/ml; p-value < 0.0001]. In addition, 42 of the 144 patients (29.2%) compared with 25 of the 244 controls (10.2%) showed TFPI concentrations below the 10^th age-dependent percentiles. Compared to baseline values 78.6% of children with total TFPI Ag < 10^th percentiles showed a low response to enoxaparin administration, whereas in children with normal baseline TFPI values 30% show a low TFPI release (p= 0.007). Multivariate analysis adjusted for the presence of established prothrombotic risk factors showed a significantly increased odds ratio (OR) and 95% confidence interval (CI) for patients with ST [OR/CI: 3.8/2.2-6.6; p< 0.0001]. Data shown here give evidence that total TFPI concentrations below the 10^th age-dependent percentiles independently increase the risk of ST in Caucasian children 3.8-fold.

Keywords

TFPI - factor V G1691A - lipoprotein (a) - paediatric thromboembolism

Full Text

References

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