Pathogenetic approach to venous thrombosis markers examination
The review summarizes experimental and clinical findings decrypting the mechanisms that initiate venous thrombosis. It is still relevant to consider the pathogenesis of venous thrombosis within the frames of the classic Virchow’s triad, and the mechanisms of interrelation of its separate mechanisms - changes in blood composition, blood flow, or alterations of the blood vessel wall - becomes more clear. Changes in the blood constituents include the amount and functional state of proteins and hemostasis system cells. Among the important changes in blood flow are blood flow rate, affecting the cells and coagulation proteins transport to the site and from the site of thrombosis, and the local shear stress, modulating adhesion and procoagulant activity of endothelium and platelets. Vascular wall provides tissue factor, which is the initiator of blood coagulation; phospholipid surface of cell membranes and microvesicles for assembling coagulation enzyme complexes, as well as adhesion proteins for the blood platelets and leukocytes «capturing». Decreased venous blood outflow and stasis, causing the local hypoxia, are associated with procoagulant changes in blood cells: the expression of P-selectin on endothelium increases, leading to the accumulation of leukocytes and cell microvesicles containing the initiator of blood coagulation - tissue factor. The local concentration of activated clotting factors increases, which along with anticoagulant activity alterations initiates progressing fibrin formation and thrombogenesis. Marking out the key mechanisms allows using them as the potential markers for diagnosing venous thrombosis risk. Among them are cell derived microparticles, cytokines, P-selectin that are investigated as possible indicators of deep vein, pulmonary, cancer associated thrombosis.