fondaparinux and Metabolic-Syndrome

Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.

Topics: Animals; Anticoagulants; Aspirin; Female; Fondaparinux; Heparin; Humans; Metabolic Syndrome; Polysaccharides; Pregnancy; Venous Thromboembolism; Warfarin

In a model of acute inflammation, Factor Xa inhibitors have been reported not only to suppress the coagulation system but also to exert anti-inflammatory effects. However, this has not been experimentally demonstrated in a model of chronic inflammation. Recent studies demonstrated that vascular inflammation in the metabolic syndrome plays major roles in the development of thrombotic diseases. Therefore, we examined the anti-inflammatory effects of fondaparinux, a Factor Xa inhibitor, in a mouse model of the metabolic syndrome, looking at both leukocyte adhesion on the vascular endothelium and thrombus formation.. Following clamping of the mesenteric vein for 20 min in the KK-A(y) mouse, mice were administered by subcutaneous injection either low-dose or high-dose fondaparinux or placebo (n = 10 in each group. Microscopic observation of the intestinal microcirculation was carried out. In another series, blood samples were taken and measured for blood cell counts and organ damage markers (n = 6 in each).. Both leukocyte adherence and thrombus formation were inhibited by treatment with fondaparinux. Red blood cell and white blood cell counts were maintained better in high-dose group. Levels of alanine aminotransferase (ALT) were significantly reduced in both low-dose and high-dose groups (P < 0.05 and 0.01, compared with control, respectively).. Factor Xa inhibitor attenuates leukocyte adhesion and leukocyte-platelet conjugate formation in a mouse model of the metabolic syndrome. These effects appeared to be related to both inhibition of thrombus formation and reduction in markers of organ damage.

Topics: Animals; Anti-Inflammatory Agents; Anticoagulants; Blood Cell Count; Cell Adhesion; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Leukocytes; Metabolic Syndrome; Mice; Polysaccharides; Thrombosis