Some indicators of hemostasis and mortality from thrombotic complications in patients with CKD stage VD who were treated by programmed hemodialysis (five-year follow-up)

Abstract

Annotation. Thrombotic complications in patients with stage VD chronic kidney disease (CKD), treated by program hemodialysis is one of the causes of high mortality in this category of patients; its major pathogenetic component proved to be hemostatic system disturbances characterized by systemic activation of blood clotting process leading to the development of thrombophilia. Objective – to study the biochemical molecular markers of hemostasis in patients with stage VD CKD, treated by program hemodialysis, and to determine their long-term effect on the development of thrombotic complications and mortality. The study included 88 patients (52 males and 36 females) aged 26 to 65 years with stage VD CKD, treated by program hemodialysis. The patients were followed up for five years. Soluble fibrin (sF) level was determined by two-site enzyme-linked immune-sorbent quantitative assay; D-dimer – by enzyme immunoassay using specific monoclonal antibodies to D-dimer epitopes; protein C (pC) activity in blood plasma was estimated by its activation with copperhead snake venom followed by spectrophotometry with wavelength 405 nm. Blood plasma fibrinogen was determined using thrombin-like enzyme Antsistron-H by spectrophotometry with wavelength 280 nm. Blood plasma fibrinolytic activity was evaluated by the relationship between D-dimer and soluble fibrin. Processing of materials was carried out using the methods of variation statistics and correlation analysis. During five years of follow up there were 13 deaths (14.8%), 7 among males and 6 among females, caused by thrombotic complications. The main thrombotic complications were myocardial infarction (6), ischemic stroke (4), mesenteric thrombosis (2) and disseminated intravascular coagulation syndrome (DIC) (1) (according to pathomorphological data). The patients of general group were found to have significantly increased sF level, decreased pC as compared to the control group, as well as twofold increase of fibrinogen concentration along with decreased D-dimer/sF ratio and no response of D-dimer to increased soluble fibrin level. The tendency of D-dimer/sF ratio to increase in those who died because of thrombotic complications could be indicative of microthrombosis with formation of fibrin derivatives along with mild activation of fibrinolysis. Correlation relationships between soluble fibrin and D-dimer, fibrinogen and protein C in general group were assessed, and the following data were obtained: medium direct relationship between soluble fibrin and D-dimer (r= 0.56) (p<0.001), and absence of correlation with fibrinogen (r= -0.12) and protein C (r= -0.10) (p˃0.1). Besides, strong positive correlation was demonstrated between D-dimer and soluble fibrin (r= 0.87) (p<0.001), and moderately negative one between D-dimer and protein C (r= -0.21) (p<0.05). It should be noted that in patients with thrombotic complications, positive correlations between soluble fibrin and D-dimer become stronger (r= 0.51) (p<0.001), as well as negative ones between soluble fibrin and protein C (r= -0.22) (p<0.05). Depressive state of anticoagulant component along with activation of coagulation factors are supposed to be one of the indicators predicting thrombophilia in this category of patients.