Bodnar P. Pathogenetic and structural-functional patterns of thromboembolic complications development in case of oncopathology

The dissertation suggests a theoretical overview and new solution to the problem of pathogenesis of venous thromboses in cancer patients with justification of the role of remodelling of the vascular wall and muscles of the leg and thigh in the occurrence, course and complications of venous thromboses. On the basis of complex studies of simulated DVT and carcinogenic intoxication of experimental animals and morphological studies of the venous wall and striated muscles of the lower limbs in cancer patients who died as a result of pulmonary embolism (PE), new links in the pathogenesis of venous thromboembolic complications were clarified and the main principles of the pathogenetic approach to their prevention and treatment were suggested. The new morphometric data were obtained and an analysis of the structural components of striated muscles and endotheliocytes of the haemomicrocirculatory bed in DVT of the lower extremities of patients with oncology was performed. It was proved that one of the significant risk factors for venous thromboembolic complications in patients with oncology is endothelial dysfunction, which is manifested by degenerative damage to endothelial cells and their desquamation, microcirculatory disorders, in particular, venular congestion with dystonia of their lumen, interstitial and perivascular oedema, infiltrative damage to the vascular wall by neutrophils and histiocytes with the formation of parietal thrombi and heterogeneous manifestations of remodelling of striated muscle fibres with the formation of atrophic-hypertrophic and contractile changes, homogenization of sarcoplasm and myocytolysis. The pathogenetic role of metabolic predictors of endothelial dysfunction in the development of DVT and its complications, in particular, the imbalance of the peroxide-antioxidant system and the haemostasis system in different periods of the course of thrombotic complications with underlying oncogenic intoxication, was established experimentally. Hypercoagulation occurs in combination with pronounced metabolic disorders, which is confirmed by the increased concentration in the blood of toxic products of lipid peroxidation, medium-molecular peptides, an increase in the concentration of the Lp-PLA2 factor in the blood, and a decrease in antioxidant protection. On the basis of the study of the features of submicroscopic changes in the endothelial lining, the level of products of lipid peroxidation, medium-mass molecules, the concentration of the Lp-PLA2 factor in the blood, the coagulation and anticoagulation system of the blood under the conditions of experimental carcinogenic intoxication, the conceptual validity of the early diagnosis of venous thrombosis, as well as the essence of the pathogenesis of venous thromboembolic complications in oncology were proved for the first time.