title: Arg506 to Gln mutation in the factor V gene causes poor fibrinolytic response in children after venous occlusion.
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).
authors.affiliation: Department of Paediatrics, University Hospital Münster, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.forename: M
authors.initials: M
authors.lastname: Binder
authors.forename: A
authors.initials: A
authors.lastname: Dübbers
authors.forename: B
authors.initials: B
authors.lastname: Kehrel
authors.forename: H G
authors.initials: HG
authors.lastname: Koch
authors.forename: H
authors.initials: H
authors.lastname: Veltmann
authors.forename: H
authors.initials: H
authors.lastname: Vielhaber
mesh_terms: 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
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D005973:Glutamine; D005165:Factor V; D001120:Arginine; D010959:Tissue Plasminogen Activator