Arginine506 to glutamin mutation in the factor V gene in infancy and childhood: evidence of fibrinolytic impairment

UNLABELLED: Resistance to activated protein C (APCR), in the majority of cases due to arginine506 (Arg506) to glutamine (Gln) mutation in the factor V gene, has emerged as the most important hereditary cause of venous thrombo-embolism. To determine to what extent this relatively common gene mutation influences the fibrinolytic system we investigated a population of APC resistant children (n = 65) in comparison with a control group of sex- and age-matched healthy children (n = 100). Compared to the controls, plasma levels of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor (PAI) 1 antigen, D-Dimer and enhanced thrombin generation were significantly (P < 0.0001) increased in children with the common factor V mutation. No difference was found between symptomatic and non-symptomatic children. Whether high concentrations of t-PA, u-PA and PAI 1 antigen can predict future vascular occlusion in children with APCR requires a more extensive multicentre study.

CONCLUSION: Our data indicate that hypercoagulability in children with the Arg506 to Gln mutation in the factor V gene is mainly attributed to the genetic aetiology of the disease.