title: Increased plasminogen activator inhibitor results in a hypofibrinolytic state in adolescents with obesity: in vivo and ex vivo evidence.
abstract: Obesity in adolescents increases their risk for deep vein thrombosis. The objectives of this study were to determine potential mechanisms for thrombotic risk by investigating the fibrinolytic pathway in a sample of adolescents with and without obesity. Thirty-seven adolescents with obesity and 16 normal weight age-matched controls were recruited. Plasma levels of components of the fibrinolytic system were measured in addition to a Global Haemostasis Potential assay (GHP), which assesses plasma capacity to generate and lyse a fibrin clot. Levels of plasminogen activator inhibitor (PAI) and tissue plasminogen activator (tPA)/PAI complexes were increased in adolescents with obesity when compared to normal weight controls. There was a significant inverse association of increasing PAI with a decrease in plasmin-antiplasmin complexes. The GHP in obese adolescents displayed a hypofibrinolytic response with a markedly increased t½clot lysis time, as well as an increase in fibrin clot density as indicated by increased absorbance at maximum peak height. In the obese group, immunodepletion of PAI decreased both t½lysis time and absorbance at maximum peak height. We have shown in vivo and ex vivo there is a hypofibrinolytic state in obese adolescents and have established the hypofibrinolytic state is due to increased PAI levels.
authors.affiliation: University of Alberta, Edmonton, AB, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dietrich
authors.affiliation: University of Alberta, Edmonton, AB, Canada.|Stollery Children's Hospital, Edmonton, AB, Canada.
authors.forename: Geoff D C
authors.initials: GD
authors.lastname: Ball
authors.affiliation: University of Alberta, Edmonton, AB, Canada. lesley.mitchell@albertahealthservices.ca.|Stollery Children's Hospital, Edmonton, AB, Canada. lesley.mitchell@albertahealthservices.ca.
authors.forename: Lesley G
authors.initials: LG
authors.lastname: Mitchell
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood*; D015849:Plasminogen Inactivators / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator
keywords: adolescents; deep vein thrombosis; fibrinolysis; obesity; plasminogen activator inhibitor