Arg506 to Gln mutation in the factor V gene causes poor fibrinolytic response in children after venous occlusion

Thromb Haemost. 1997 Sep;78(3):1115-8.

Abstract

To determine to what extent the Arg506 to Gln mutation in the factor V gene influences the fibrinolytic response after 20 min venous occlusion (VO) we investigated a population of APC resistant children (n = 60) and a group of age-matched healthy controls (n = 25). After 20 min VO, symptomatic (n = 30) carriers of the common factor V mutation showed significantly reduced t-PA activities compared with asymptomatic (n = 30) carriers (p <0.0001) and healthy controls (p <0.0001). In contrast, PAI 1 activity was significantly (p <0.0001) higher before and after VO in children with the factor V mutation compared with healthy children. No difference was found between symptomatic and asymptomatic probands. A significantly lower PAI 1 antigen decrease along with a lower t-PA antigen release was found in the APC resistant children compared with the controls. No significant difference was seen between individuals with and without previous vascular insults. As the lack of t-PA activity after VO in symptomatic carriers is the most conspicuous result, we suggest that the factor V gene mutation itself might induce the fibrinolytic impairment by increasing the thrombin levels and thus increasing the recently described thrombin-activable fibrinolysis inhibitor (TAFI).

MeSH terms

  • Arginine / genetics
  • Child
  • Factor V / genetics*
  • Fibrinolysis* / genetics
  • Glutamine / genetics
  • Humans
  • Plasminogen Activator Inhibitor 1 / blood
  • Point Mutation*
  • Protein C / physiology*
  • Thrombophlebitis / blood*
  • Thrombophlebitis / genetics
  • Tissue Plasminogen Activator / metabolism

Substances

  • Plasminogen Activator Inhibitor 1
  • Protein C
  • Glutamine
  • Factor V
  • Arginine
  • Tissue Plasminogen Activator