Thrombosis in Children

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Abstract

Aims: The general objective was to further elucidate thromboembolic disease in children and thereby help improve the care of these patients. More specific aims were as follows: to determine what children are affected by thrombosis; to discern any gender or age differences related to thrombosis; to identify prothrombotic risk factors; to ascertain whether autoantibodies against coagulation proteins constitute a risk factor for childhood thrombosis; to study girls receiving estrogen treatment with regard to induced hemostatic changes and efficacy of the therapy; to investigate long-term effects on the hemostatic system in children subjected to heart surgery.
Material and methods: Children with thrombosis (Papers I and II) and children at risk of thrombosis (Papers III and IV) were investigated. In the initial study, 128 children referred for a first thrombotic event were retrospectively evaluated. In a subsequent endeavor, 57 children with thrombosis were prospectively included and evaluated for thrombotic risk factors, and patients and controls were investigated for autoantibodies. Considering children at risk, 63 girls treated with high doses of ethinyl estradiol were studied. Furthermore, 28 children with congenital heart defects were evaluated before and after Fontan surgery, and the results of follow-up global coagulation tests in patients and controls were analyzed.
Results and conclusions: The present studies showed a bimodal age distribution in pediatric thrombosis patients in Sweden, with peaks in frequency rates during the neonatal period and in adolescence. The girls:boys ratio was 2:1. Of the children with thrombosis, 84% had acquired risk factors and they showed a significantly increased prevalence of inherited thrombophilia. Also, autoantibodies against prothrombin were significantly more often detected than in controls, suggesting immunological pathogenesis. Pediatric thrombosis often seem to be elicited by a combination of risk factors. Girls receiving high-dose estrogen treatment exhibited both pro- and anticoagulation abnormalities; the estrogen therapy was most effective when started at a younger bone age, and the risk of thrombosis was <5% and considered a safe treatment in our cohort. Post-Fontan patients had a lower incidence of procoagulant abnormalities at long-term follow-up compared to before surgery, although a subset of the subjects showed evidence of elevated thrombin generation, identified by increases in APC-PCI, as compared to controls. The results indicate that prophylaxis to prevent thrombosis in these children should be individualized.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Clinical Sciences, Malmö
Supervisors/Advisors
  • Ljung, Rolf, Supervisor
  • Berntorp, Erik, Supervisor
Award date2008 Dec 13
Publisher
ISBN (Print)978-91-86059-72-9
Publication statusPublished - 2008

Bibliographical note

Defence details

Date: 2008-12-13
Time: 10:00
Place: Aulan, Clinical Research Center, Ingång 72, Universitetssjukhuset MAS, Malmö

External reviewer(s)

Name: Johnsson, Hans
Title: Ass Professor
Affiliation: Karolinska Universitetssjukhuset, Stockholm

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Subject classification (UKÄ)

  • Pediatrics

Keywords

  • Child
  • Estradiol
  • Heart Defects
  • Congenital
  • Hemostasis
  • Protein C Inhibitor
  • Risk factors
  • Thrombophilia
  • Thromboembolism
  • Autoantibodies
  • Adolescent

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