INFLUENCES OF LIPID-MODIFYING AGENTS ON HEMOSTASIS

Drugs affecting lipid metabolism may influence, to a variable extent, the hemostatic system, that is, platelet activation, fibrinogen, and f ibrinolysis. These effects may or may not be linked to the activity of these compounds on the lipid/lipoprotein profile. For this reason it may be important to consider the effects of hypolipidemic drugs on the different aspects of hemostasis, because this may allow a better unde rstanding of their clinical use, as well as, eventually, a more proper selection in individual patients. Among the major lipid-lowering agen ts, fibric acids belong to a multifaceted series of abnormal fatty aci ds known to interact with a liver nuclear receptor, in turn activating fatty acid catabolism. A similar activity may be exerted by n-3 fatty acids from fish, as well as by other chemically related or unrelated compounds. Among fibric acids all but gemfibrozil can reduce fibrinoge n levels; this last drug can, however, apparently activate fibrinolysi s. Among the selective cholesterol-lowering medications, both resins a nd HMG CoA reductase inhibitors may reduce, in some patients, over pro longed periods of treatment, platelet sensitivity to major aggregants. This effect may be seen best with non-liver-selective agents (e.g., s imvastatin), although recent data cast doubt on its constancy. A direc t comparative evaluation of different HMG CoA reductase inhibitors on platelet aggregability has never been carried out. These last drugs ma y also reduce the circulating levels of the tissue factor pathway inhi bitor (TFPI), transported by LDL in plasma, which is a potentially neg ative effect. A lipid-lowering molecule with antioxidant activity, for example, probucol, may also possibly play a role in controlling plate let activation. Probucol was recently shown to reduce the excretion of thromboxane metabolites in patients with homocystinuria. The complex pattern of effects of this molecule may, however, also suggest other m echanisms.