Target therapy for venous thrombosis: experimental extravagance or tangible future?

Abstract

Anticoagulant therapy is considered to be a treatment and prophylaxis standard for venous thrombosis (VT). Despite the high efficacy and safety of modern anticoagulants, bleeding as the side effect remains a prominent unresolved problem that can limit their use. As interrelation between immune system and coagulation is the basis of immunothrombosis, immunosuppression could be considered an alternative in the target therapy for venous thrombosis. Endothelial activation due to the blood stasis and vein wall hypoxia together with proinflammatory mediators promote essential conditions for venous thrombosis. The key points of this process are also the platelets and leukocytes activation and neutrophil extracellular traps secretion. Inhibition of intercellular interactions by the adhesion and signal molecules deletion (P-selectins, galectins, HMGB1) can fully prevent thrombosis or significantly reduce the thrombus. The same effect is observed when platelets function is suppressed by GPIbα transformation, CLEC-2 deletion or von Willebrand factor deficiency. Neutropenia contributes to a change in the thrombus structure and density, and less often prevents its formation. In addition, one of the options for the VT prevention in the experiment is the introduction of resorption mediators, which are secreted by effector cells in the process of thrombosis resolution. Target therapy appears to be a promising method based on key links in the VT pathogenesis, which may allow avoiding typical complications of anticoagulant therapy.