European Journal of Pediatrics

, Volume 155, Issue 12, pp 1009–1014

Prevalence of factor V Leiden in children with thrombo-embolism

  • I. Aschka
  • V. Aumann
  • F. Bergmann
  • U. Budde
  • W. Eberl
  • S. Eckhof-Donovan
  • S. Krey
  • U. Nowak-Göttl
  • R. Schobess
  • A. H. Sutor
  • J. Wendisch
  • R. Schneppenheim
Hematology/Oncology

Abstract

Abstract

Hereditary resistance to the anticoagulatory action of activated protein C (APC resistance, APCR) was identified as a possible new thrombophilic factor in a high percentage (17%–60%) of young adults with thrombotic events. A single missense mutation (R506Q) due to a G/A transition (G1691A) in exon 10 of the factor V gene is regarded as the causative molecular defect, resulting in factor V Leiden which is correlated with APCR. Identification of this mutation by polymerase chain reaction-based methods is easy to perform and prevents pre-analytical and analytical errors in the coagulometric assay for APCR. Since the impact of this mutation in children with thrombo-embolic disease has not been determined to date, we initiated a multi centre prevalence study in two paediatric populations, with and without thrombo-embolic events. We compared 125 paediatric patients with thrombosis, divided into three different age groups (0 to <0.5 years; >0.5 to <10 years; >10 to <18 years) with a normal population of 159 children. Although the mutation G1691A was found with an unexpectedly high prevalence of 12% in our normal controls, the prevalence was significantly higher in the age groups: 0 to <0.5 years (26%) and >10 to <18 years (30%). In patients between >0.5 and <10 years the overall prevalence was similar to that of the control group (13%). However, in patients of this age with spontaneous thrombosis, G1691A was also a significant risk factor (5/17≊29%). Homozygosity for G1691A was detected in three patients but not in the control group. Including deficiencies of protein C, protein S, antithrombin, and the presence of anti-phospholipid antibodies, thrombosis was correlated with endogenous thrombophilic factors in 38/125 patients (30.4%).

Conclusion

Our results emphasize the impact of factor V Leiden on thrombogenesis in children. However, the significance is age-dependent and may reflect the different physiology of haemostasis in the three age groups. The diagnostic workup of children with thrombosis should inelude tests for factor V Leiden. The correlation of factor V Leiden with the clinical course of thrombo-embolism in children is essential to establish rational guidelines for therapy and prophylaxis of APCR-related thrombosis which are not yet available.

Key words

Factor V Leiden Protein C Protein S Thromboembolism Childhood 

Abbreviations

APC

activated protein C

APCR

activated protein C resistance

PCR

polymerase chain reaction

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • I. Aschka
    • 1
  • V. Aumann
    • 2
  • F. Bergmann
    • 3
  • U. Budde
    • 4
  • W. Eberl
    • 5
  • S. Eckhof-Donovan
    • 6
  • S. Krey
    • 1
  • U. Nowak-Göttl
    • 7
  • R. Schobess
    • 8
  • A. H. Sutor
    • 9
  • J. Wendisch
    • 10
  • R. Schneppenheim
    • 1
  1. 1.Universitäts-Kinderklinik KielKielGermany
  2. 2.University Children's Hospital MagdeburgMagdeburgGermany
  3. 3.Children's HospitalMedical School HannoverHannoverGermany
  4. 4.General Hospital HarburgHamburgGermany
  5. 5.Children's Hospital BraunschweigBraunschweigGermany
  6. 6.University Children's Hospital DüsseldorfDüsseldorfGermany
  7. 7.University Children's Hospital MünsterMünsterGermany
  8. 8.University Children's Hospital HalleHalleGermany
  9. 9.University Children's Hospital FreiburgFreiburgGermany
  10. 10.University Children's Hospital DresdenDresdenGermany

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