Annotation. Clinical observations indicate that one of the rather important mechanisms in the pathogenesis of complications in CKD stage VD are disorders in the hemostatic system leading to the development of thrombophilia. Comorbidity in this category of patients significantly worsens the prognosis due to the potentiation of hypercoagulation, which, as a comorbid syndrome, accelerates morphological changes in the kidneys, contributes to the deposition of fibrin in the glomeruli and the development of thrombosis. The aim of the study was to study the indices of the main links of hemostasis depending on some comorbid conditions (acute inflammation, secondary hyperparathyroidism, hepatitis B and C). The study involved 52 men and 36 women with CKD stage VD, who were on programmed hemodialysis, in whom the levels of soluble fibrin, D-dimer, fibrinogen, protein C, indicators of hemostatic potential in these comorbid conditions were determined. Statistical processing of materials was performed using the methods of variation statistics.It was determined that the presence of a fast phase of inflammation enhances the processes of hypercoagulability, and a high level of parathyroid hormone (˃800 pg/ml) in combination with hyperphosphoremia slightly increases the level of fibrinogen. Infection with hepatitis C significantly increases the level of soluble fibrin, and infection with hepatitis B decreases the level of protein C. The study and implementation of a comprehensive assessment of the state of hemostasis in patients with CKD stage VD complicated by comorbid diseases makes it possible to identify imbalances in the pro- and anticoagulation system.
Annotation. Violations in the hemostatic system of patients with chronic kidney disease (CKD) of the VD stage treated with program hemodialysis are associated with a high thrombotic risk. Comprehensive studies of the possible causes and predictors of thrombophilia can improve the therapeutic and prophylactic measures to combat thrombotic complications. The search for available methods for predicting these complications is very relevant. The goal is to develop a method for predicting the development of thrombotic complications in this category of patients, which would allow identifying the degree of hemostasis disorders. We examined 88 patients with CKD VD, treated with program hemodialysis, who determined the fibrinolytic potential and the level of soluble fibrin and D-dimer by enzyme immunoassay. It is proposed to use the developed fibrinolytic coefficient (Fc) to predict thrombotic complications. It was found that the proposed method for assessing hemostasis using Fc makes it possible to objectively characterize the state of the coagulation link and can serve as an indicator of thrombotic risk.
Thrombotic complications, associated with hemostatic system disturbances in patients with stage VD chronic kidney disease (CKD), occur rather frequently. Hence, the search of early available biological markers in diagnosis of this complication is of great significance. Objective – to study coagulation potential of blood plasma in patients with stage VD CKD, treated by program hemodialysis, and to determine the markers of thrombotic risk. 88 patients (aged 26–65) with stage VD CKD, treated by program hemodialysis, were studied. Hemostatic potential of blood was determined by spectrophotometry; soluble fibrin level — by two-site enzyme-linked immune-sorbent quantitative assay; D-dimer — by enzyme immunoassay using monoclonal antibodies to D-dimer epitopes; protein C activity — by spectrophotometry with wavelength 405 nm; fibrinogen contents — by spectrophotometry with wavelength 280 nm. Statistical processing was performed by methods of variation statistics and correlation analysis. All patients were found to have significant increase of soluble fibrin level (4.03±0.15÷4.62±0.31 mg/ml) (р <0.001), but there was a group of patients (n=25), who demonstrated increased coagulation potential, (р <0.001), significantly prolonged fibrinolysis (р <0.001) and increased soluble fibrin concentration (5.36±0.61÷5.78±0.82 µg/ml) (р <0.001) along with the tendency to decreased C protein level and no response of D-dimer to increased soluble fibrin level. Detected changes in coagulation properties of blood plasma can serve the markers of thrombotic risk. Thus, the patients with stage VD CKD, treated by program hemodialysis, have high risk of thrombosis, associated with high concentration of soluble fibrin and fibrinogen. But in this category of patients, rather low fibrinolytic potential, as well as the level of natural anticoagulant — C protein — is observed. The studied homeostatic parameters can be used as the markers of thrombotic risk.
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.
1RESEARCH INSTITUTE OF REHABILITATION OF NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE 2NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE 3PALLADIN INSTITUTE OF BIOCHEMISTRY OF NAS OF UKRAINE, KYIV, UKRAINE ABSTRACT The aim: To study the status of pro- and anticoagulant components of hemostasis in patients with stage VD CKD depending on residual renal function. Materials and methods: 88 patients with stage VD CKD were studied, 16 of them had preserved residual renal function (RRF). Hemostatic parameters – soluble fibrin, D-dimer and protein C – were determined in the patients. Results: Significant increase in soluble fibrin and fibrinogen levels along with depressive reaction of D-dimer and protein C were found in patients with stage VD CKD having lost RRF. Preserved RRF in those patients had positive influence on hemostatic profile, decreasing the degree of hypercoagulation. Conclusions: 1. In long term dialysis patients with stage VD CKD and lost RRF, significantly increased levels in soluble fibrin and fibrinogen along with decreased D-dimer concentration were found, being a key factor in the development of thrombotic complications. 2. There was significant decrease in protein C activity in patients with lost RRF. 3. Preserved RRF in patients with stage VD CKD had positive influence on hemostatic profile.
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