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Familial elevated factor VIII in children with symptomatic venous thrombosis and post-thrombotic syndrome: results of

Wolfhart Kreuz1, Monika Stoll, Ralf Junker

  • 1Department of Paediatric Haematology, Oncology, and Haemostaseology, University Children's Hospital, Frankfurt/Main, Germany.

Arteriosclerosis, Thrombosis, and Vascular Biology
|May 20, 2006
PubMed

Insights

Elevated levels of factor VIII (FVIII) are linked to an increased risk of deep vein thrombosis (DVT) in children. This genetic predisposition, particularly for FVIII:C, highlights the importance of FVIII in pediatric thrombosis.

Area of Science:

  • Pediatric Hematology
  • Thrombosis Research
  • Genetics of Hemostasis

Background:

  • Venous thromboembolism (VTE) in children, including deep vein thrombosis (DVT) and recurrent DVT, poses significant health risks.
  • Post-thrombotic syndrome (PTS) is a common complication following DVT in pediatric populations.
  • The role of coagulation factor VIII (FVIII) in the pathogenesis of pediatric VTE requires further elucidation.

Purpose of the Study:

  • To investigate the association between factor VIII (FVIII) levels and the occurrence of DVT, PTS, and recurrent DVT in children.
  • To determine the heritability and environmental influences on FVIII levels in pediatric patients with VTE.
  • To assess the clinical significance of elevated FVIII levels in pediatric venous thrombosis.

Main Methods:

  • Factor VIII antigen (FVIII:Ag) and activity (FVIII:C) levels were measured in pediatric patients with VTE and age/gender-matched healthy controls.
  • Heritability (h2) and household (c2) components of FVIII levels were estimated using the variance component method (SOLAR).
  • Odds ratios (OR) were calculated for elevated FVIII levels (above the 90th percentile) adjusted for fibrinogen.

Main Results:

  • Children with DVT exhibited significantly higher median FVIII:Ag and FVIII:C levels compared to controls.
  • Elevated FVIII levels were associated with a substantially increased odds ratio for DVT.
  • Heritability estimates indicated a strong genetic contribution to FVIII:Ag and FVIII:C levels, with a predominant genetic influence on FVIII:Ag variance.

Conclusions:

  • Elevated factor VIII levels are a significant risk factor for deep vein thrombosis in children.
  • The findings underscore the genetic basis of high FVIII levels and their contribution to pediatric VTE.
  • Understanding FVIII's role can inform risk assessment and potentially guide preventative strategies in pediatric thrombosis.
Abstract

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