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.
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Abbreviations
- APC :
-
activated protein C
- APCR :
-
activated protein C resistance
- PCR :
-
polymerase chain reaction
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Aschka, I., Aumann, V., Bergmann, F. et al. Prevalence of factor V Leiden in children with thrombo-embolism. Eur J Pediatr 155, 1009–1014 (1996). https://doi.org/10.1007/BF02532520
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DOI: https://doi.org/10.1007/BF02532520