Evidence that fibrinolytic changes in paediatric obesity translate in a hypofibrinolytic state. Relative contribution of TAFI and PAI-1.
Summary of "Evidence that fibrinolytic changes in paediatric obesity translate in a hypofibrinolytic state. Relative contribution of TAFI and PAI-1."
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.
Affiliation
Mario Colucci, Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale e Sperimentale, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy, Tel.: +39 080 5478471, Fax: +39 080 5478524, E-mail: mario.colucci@dimo.uniba.it.
Journal Details
This article was published in the following journal.
Name: Thrombosis and haemostasis
ISSN: 0340-6245
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22740053
- DOI: http://dx.doi.org/10.1160/TH11-12-0864
Medical and Biotech [MESH] Definitions
Obesity, Abdominal
A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes, hypertension and METABOLIC SYNDROME X.
Prejudice
A preconceived judgment made without adequate evidence and not easily alterable by presentation of contrary evidence.
Obesity, Morbid
The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.
Anti-obesity Agents
Agents that increase energy expenditure and weight loss by neural and chemical regulation. Beta-adrenergic agents and serotoninergic drugs have been experimentally used in patients with non-insulin dependent diabetes mellitus (NIDDM) to treat obesity.
Brinolase
A fibrinolytic and thrombolytic enzyme from Aspergillus oryzae. EC 3.4.99.-.
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