title: Prevalence of factor V Leiden in children with thrombo-embolism.
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 approximately equal to 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%).
  
  
  CONCLUSIONS
  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 include 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.
authors.affiliation: Universitäts-Kinderklinik Kiel, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Aschka
authors.forename: V
authors.initials: V
authors.lastname: Aumann
authors.forename: F
authors.initials: F
authors.lastname: Bergmann
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: W
authors.initials: W
authors.lastname: Eberl
authors.forename: S
authors.initials: S
authors.lastname: Eckhof-Donovan
authors.forename: S
authors.initials: S
authors.lastname: Krey
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.forename: R
authors.initials: R
authors.lastname: Schobess
authors.forename: A H
authors.initials: AH
authors.lastname: Sutor
authors.forename: J
authors.initials: J
authors.lastname: Wendisch
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D020151:Protein C Deficiency; D012307:Risk Factors; D013923:Thromboembolism / Q000235:genetics* / Q000378:metabolism
chemical_list: C095381:factor V Leiden; D005165:Factor V