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


CONCLUSIONS
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.
Nowak-Göttl
U
U
Westfälische Wilhelms-Universität, Department of Paediatrics, Paediatric Haematology and Oncology, Münster, Germany.
Vielhaber
H
H
Grohmann
J
J
Schneppenheim
R
R
Koch
H G
HG
D000293:Adolescent; D001120:Arginine / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000235:genetics*; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009842:Oligopeptides / Q000502:physiology; D011486:Protein C / Q000502:physiology; D013917:Thrombin / Q000378:metabolism; D013924:Thrombophlebitis / Q000097:blood / Q000235:genetics*
D005338:Fibrin Fibrinogen Degradation Products; D009842:Oligopeptides; D011486:Protein C; C036309:fibrin fragment D; C047135:protein C activator peptide; D005973:Glutamine; D005165:Factor V; D001120:Arginine; D013917:Thrombin