The main pathogenetic mechanisms of hypercoagulation in diabetes and the possibility of its drug correction

Abstract

Disorders in the blood coagulation system play an important role in the development of cardiovascular pathology in diabetes. Factors that cause them are hyperglycemia, insulin deficiency, insulin resistance, dyslipidemia, oxidative stress. The most significant changes are observed in the vascular-platelet link of hemostasis. Diabetes is characterized by morphological and functional changes in the endothelium of blood vessels. The activity of platelets increases, which is manifested by their high level of spontaneous aggregation and increased sensitivity to the action of activating factors. The role in the disturbance of hemostasis is played by increasing the activity of the von Willebrand factor, reflecting damage to endothelial cells. Diabetes is characterized by an increase in the activity of plasma clotting factors (I, II, III, VII, VIII, IX, XI, XII and XIII), activation of the callicrein-kinin system. In some cases, this correlates with the development of complications of diabetes. Characteristic disorders in the coagulation inhibition system are a decrease in the activity of antithrombin III, reduced formation of thrombin-antithrombin complexes, reduction of thrombomodulin and protein C. In diabetes, there is a decrease in fibrinolysis, due to a decrease in the expression of tissue activator plasminogen and an increase in the level of the inhibitor of the activator plasminogen. The possibilities of drug correction of hypercoagulation factors in diabetes are to achieve glycemic control with sugar-reducing drugs and elimination of dyslipidemia through hypolipidemic therapy. The most well-studied sugar-lowering drug that improves the state of the blood clotting system is metformin. The system of hemostasis in diabetic patients is positively affected by statins both due to the direct hypolipidemic effect, and by improving endothelial function and increasing fibrinolysis.

Keywords

diabetes mellitus / platelets / plasma clotting factors / inhibition of coagulation / fibrinolysis / glycemic control / dyslipidemia / metformin / statins

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Kryukov E.V., Kuchmin A.N., Umanskaya E.P., Nagorny M.B., Shevelev A.A.