title: Evidence that fibrinolytic changes in paediatric obesity translate into a hypofibrinolytic state: relative contribution of TAFI and PAI-1.
abstract: Paediatric obesity, like adulthood obesity, is associated with an increase of fibrinolysis inhibitors. No study, however, has evaluated the impact of these changes on plasma fibrinolytic capacity. We investigated plasma fibrinolysis and the role therein of the fibrinolytic changes associated with obesity in 59 obese children (body mass index > 95th percentile) and 40 matched controls. Fibrinolysis was investigated by measuring  1) the plasma levels of relevant fibrinolytic factors; 2) the  in vitro  fibrinolytic capacity under different conditions, using a microplate plasma clot lysis assay; 3) the circulating levels of markers of clotting and fibrinolysis activation. Plasminogen activator inhibitor 1 (PAI-1), total thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen levels were higher in obese children as compared to controls (p<0.01). Plasma clots from obese children lysed significantly slower than control clots when exposed to exogenous plasminogen activator, indicating a greater resistance to fibrinolysis. By the use of a selective inhibitor of activated TAFI and by regression analyses we found that fibrinolysis resistance in obese samples was attributable to PAI-1 increase and to enhanced TAFI activation. The ratio between the circulating levels of D-dimer and thrombin-antithrombin complex, a marker of  in vivo  fibrinolysis, was significantly lower in obese children, suggesting a reduced fibrinolytic efficiency. These data indicate that paediatric obesity is associated with a hypofibrinolytic state which might contribute to the increased thrombotic risk associated with this condition.
authors: Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale e Sperimentale, Bari, Italy.
authors: Fabrizio
authors: F
authors: Semeraro
authors: Paola
authors: P
authors: Giordano
authors: Maria F
authors: MF
authors: Faienza
authors: Luciano
authors: L
authors: Cavallo
authors: Nicola
authors: N
authors: Semeraro
authors: Mario
authors: M
authors: Colucci
mesh_terms: D001777:Blood Coagulation; D001779:Blood Coagulation Factors; D001780:Blood Coagulation Tests; D015992:Body Mass Index; D025901:Carboxypeptidase B2 / Q000096:biosynthesis; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis; D005342:Fibrinolysis / Q000276:immunology*; D006801:Humans; D008297:Male; D009765:Obesity / Q000150:complications / Q000628:therapy; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012044:Regression Analysis
chemical_list: D001779:Blood Coagulation Factors; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D005340:Fibrinogen; D025901:Carboxypeptidase B2