Prevalence of factor V Leiden in children with thrombo-embolism
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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%).
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 wordsFactor V Leiden Protein C Protein S Thromboembolism Childhood
activated protein C
activated protein C resistance
polymerase chain reaction
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- 2.Andrew M (1995) Developmental haemostasis: relevance to thrombo-embolic complications in paediatric patients. Thromb Haemostas 74: 415–425Google Scholar
- 6.Arnout J, Vanrusselt M, Vermylen J (1995) Resistance to activated protein C in a population of patients with antiphospholipid antibodies. Thromb Haemostas 73:1275Google Scholar
- 7.Bandello F, Vigano-D'Angelo S, Parlavecchia M, Tavola A, Della-Valle P Brancato R, D'Angelo A (1994) Hypercoagulability and high lipoprotein(a) levels in patients with central retinal vein occlusion. Thromb Haemostas 72: 39–43Google Scholar
- 14.Dahlbäck B (1995) New molecular insights into the genetics of thrombophilia. Resistance to activated protein C caused by Arg 506 to Gln mutation in factor V as a pathogenetic risk factor. Thromb Haemostas 74: 139–148Google Scholar
- 18.David M, Manco-Johnson M, Andrew M (1995) Diagnosis and treatment of venous thrombo-embolism in children and adolescents. On behalf of the subcommittee on peri-natal haemostasis of the scientific and standardization committee of the ISTH. Thomb Haemostas 74: 791–792Google Scholar
- 19.Faioni EM, Boyer-Neumann C, Franchi F, Wolf M, Meyer D, Mannucci P (1994) Another protein S functional assay is sensitive to resistance to activated protein C. Thromb Haemostas 72: 643–651Google Scholar
- 26.Koster T, Rosendaal FR, Ronde H de, Briet E, Vandenbroucke JP, Bertina RM Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 342: 1503–1506Google Scholar
- 28.Mannucci PM, Tripodi A (1987) Laboratory screening of inherited thrombotic syndromes. Thromb Haemostas 57: 247–251Google Scholar
- 29.Nowak-Göttl U, Aschka I, Koch HG, Boos J, Dockhorn-Dworniczak B, Deufel T, Jürgens H, Kohlhase B, Kuhn N, Laupert A, Rath B, Wolff JEA, Schneppenheim R (1995) Resistance to activated protein C (APCR) in children with acute lymphoblastic leukaemia — the need for a prospective multicentre study. Blood Coag Fibrinol 6: 761–764Google Scholar
- 32.Nuss R, Hays T, Manco-Johnson M (1995) Childhood thrombosis. Paediatrics 96: 291–294Google Scholar
- 35.Schmidt B, Andrew M (1995) Neonatal thrombosis: report of a prospective Canadian and international registry. Paediatrics 96: 939–943Google Scholar