PREVALENCE OF FACTOR-V LEIDEN IN CHILDREN WITH THROMBOEMBOLISM

Hereditary resistance to the anticoagulatory action of activated prote in C (APC resistance, APCR) was identified as a possible new thromboph ilic factor in a high percentage (17%-60%) of young adults with thromb otic events. A single missense mutation (R506Q) due to a G/A transitio n (G1691A) in exon 10 of the factor V gene is regarded as the causativ e molecular defect, resulting in factor V Leiden which is correlated w ith APCR. Identification of this mutation by polymerase chain reaction -based methods is easy to perform and prevents pre-analytical and anal ytical errors in the coagulometric assay for APCR. Since the impact of this mutation in children with thrombo-embolic disease has not been d etermined to date, we initiated a multi centre prevalence study in two paediatric populations, with and without thrombo-embolic events. We c ompared 125 paediatric patients with thrombosis, divided into three di fferent age groups (0 to < 0.5 years; > 0.5 to < 10 years; > 10 to < 1 8 years) with a normal population of 159 children. Although the mutati on G1691A was found with an unexpectedly high prevalence of 12% in our normal controls, the prevalence was significantly higher in the age g roups: 0 to < 0.5 years (26%) and > 10 to < 18 years (30%). In patient s between > 0.5 and < 10 years the overall prevalence was similar to t hat of the control group (13%). However, in patients of this age with spontaneous thrombosis, G1691A was also a significant risk factor (5/1 7 congruent to 29%). Homozygosity for G1691A was detected in three pat ients but not in the control group. Including deficiencies of protein C, protein S, antithrombin, and the presence of anti-phospholipid anti bodies, thrombosis was correlated with endogenous thrombophilic factor s in 38/125 patients (30.4%). Conclusion Our results emphasize the imp act of factor V Leiden on thrombogenesis in children. However, the sig nificance is age-dependent and may reflect the different physiology of haemostasis in the three age groups. The diagnostic workup of childre n with thrombosis should include tests for factor V Leiden. The correl ation 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 .