Arg506 to Gln mutation in the factor V gene causes poor fibrinolytic response in children after venous occlusion.
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).
Nowak-Göttl
U
U
Department of Paediatrics, University Hospital Münster, Germany.
Binder
M
M
Dübbers
A
A
Kehrel
B
B
Koch
H G
HG
Veltmann
H
H
Vielhaber
H
H
D001120:Arginine / Q000235:genetics; D002648:Child; D005165:Factor V / Q000235:genetics*; D005342:Fibrinolysis / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017354:Point Mutation; D011486:Protein C / Q000502:physiology*; D013924:Thrombophlebitis / Q000097:blood* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D005973:Glutamine; D005165:Factor V; D001120:Arginine; D010959:Tissue Plasminogen Activator