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Quantitative abnormalities of fibrinolytic system factors (tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PA-inhibitor) are often found in the patients exhibiting an idiopathic thromboembolic pathology. Exploration of fibrinolytic system is performed by taking blood samples prior and after stimulation (after venous occlusion or DDAVP injection). Patients can be "good responders" (that is presenting with an increase of fibrinolytic activity after stimulation) or "bad responders". Among these latter (that is 30 p. 100 of cases), there are two groups: patients exhibiting an increase of PA inhibitor level, this concealing fibrinolytic role of t-PA released by stimulation (20 p. 100 of cases), patients failing to present any t-PA release through endothelial cells stimulation (10 p. 100 of cases). Furthermore, an hypofibrinolysis was demonstrated a long time ago, in certain thrombogenic conditions (post-operative period, obesity, elderly patients). Hypofibrinolysis was recently demonstrated, according to such conditions, as liable to an increase in the PA inhibitor levels. As pathogenic role of hypofibrinolysis is then demonstrated, therapeutic studies reducing the PA inhibitor level or increasing the t-PA rate produced and released by endothelial cells are to be developed.

We have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 +/- 1.13, m +/- S.E.M.) were compared to age matched controls (C) (BMI: 20.2 +/- 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m +/- S.E.M.) of PA Inhibition (9 +/- 1.8 IU/ml, versus 2.88 +/- 0.29 p less than 0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 +/- 1.17 mm versus 9 +/- 0.29 p less than 0.05), higher plasma insulin (24.1 +/- 2.1. uU/ml), versus 12 +/- 1 p less than 0.01) and triglyceride (1.32 +/- 0.16 mmol/l, versus 0.8 +/- 0.08 p less than 0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 +/- 1.4, versus 9.48 +/- 2.1 p less than 0.05) in plasma insulin (18.5 +/- 0.1, versus 24.5 +/- 3.5, p less than 0.05) and plasma triglyceride (1.08 +/- 0.1, versus 1.47 +/- 0.3 p less than 0.05) and an increase in EFA (6.50 +/- 0.28, versus 5.25 +/- 0.35 p less than 0.05) were observed. No significant variation was observed in group P.