The relationship between activation of the coagulo‑fibrinolytic system and aseptic inflammation in patients with long‑term chronic thromboembolic pulmonary hypertension

Abstract

Background. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a poor prognosis. The role of monocytic-macrophage inflammation in the incomplete recanalization of acute thromboembolic pulmonary artery disease and the formation of CTEPH was shown. The role of the coagulo-fibrinolytic system in the pathogenesis of CTEPH remains controversial.Objective. To assess the activity of the coagulo-fibrinolytic system and its relationship with the level of monocytic chemotactic factor 1 (MCP-1), as well as the severity of the disease in patients with long-term CTEPH.Design and methods. The study included 44 patients diagnosed with CTEPH: 21 men (mean age 57,0 ± 11,9 years) and 23 women (mean age 53,8 ± 14,7 years). The diagnosis of CTEPH was verified according to the clinical guidelines of the Ministry of Health of the Russian Federation for the diagnosis and management of patients with pulmonary hypertension from 2020. The control group consisted of healthy donors (n = 19, mean age 51,0 ± 11,9 years, 10 men, 9 women). All patients were on anticoagulant therapy with enoxaparin sodium at a therapeutic dose of 1 mg/kg subcutaneously twice a day. The study of markers of the fibrinolysis and inflammation system was carried out by enzyme immunoassay: thrombin-activated fibrinolysis inhibitor (TAFI), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), monocytic chemotactic factor 1 (MCP-1).Results. In the CTEPH group, an increase in the level of t-PA was demonstrated — 6,06 [4,502; 8,03] vs 2,95 [2,75; 3,56] ng/ml in donors (p = 0,00001). The levels of PAI-1 and TAFI did not differ in patients (34,40 [22,47; 46,43] and 94,67 [90,03; 102,80] ng/mL, respectively) and donors (24,93 [21,41; 43,88] and 92,68 [87,99; 98,29] ng/ml, respectively) (p = 0,0970 and p = 0,233). A significant increase in the level of MCP-1 was found in patients with CTEPH compared to donors (34,95 [31,00; 42,08] vs 26,05 [20,40; 31,33] pg/ml, p = 0,016, respectively). A correlation was noted between MCP-1 and fibrinolysis indices t-PA (0,402, p = 0,046), PAI-1 (0,437, p = 0,029). Correlations of MCP-1 and fibrinolysis markers with hemodynamic and physical performance indicators are also shown: MCP-1 and SvO2 (–0,574, p = 0,002), MCP-1 and cardiac index (CI) (–0,614, p = 0,001), distance in the six-minute walk test (6MWT) and t-PA (–0,435, p = 0,006).Conclusions. As a result of the study, the relationship between MCP-1 and the activity of the coagulo-fibrinolytic system and the severity of CTEPH was demonstrated. The data obtained can be used to further study the pathogenesis of postthromboembolic syndrome and develop criteria for assessing prognosis in patients with CTEPH.