STATUS OF PRO- AND ANTICOAGULANT COMPONENTS OF HEMOSTASIS IN PATIENTS WITH STAGE VD CKD DEPENDING ON RESIDUAL RENAL FUNCTION

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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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)

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2021-25(3)-10 ◽

2021 ◽

Vol 25 (3) ◽

pp. 409-412

Author(s):

O. B. Storozhuk ◽

I. B. Seleznyova ◽

L. O. Storozhuk ◽

T. M. Platonova ◽

B. G. Storozhuk ◽

...

Keyword(s):

Blood Plasma ◽

Protein C ◽

Control Group ◽

Strong Positive Correlation ◽

General Group ◽

Soluble Fibrin ◽

Ckd Stage ◽

Thrombotic Complications ◽

D Dimer

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.

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Some indicators of hemostasis in patients with ischemic heart disease and coronary angioplasty

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2018-22(3)-09 ◽

2018 ◽

Vol 22 (3) ◽

pp. 446-449

Author(s):

N.V. Storozhuk ◽

E.V. Luhovskoy ◽

B.H Storozhuk ◽

T.M. Platonova ◽

I.M. Kolesnikov

Keyword(s):

Heart Disease ◽

Ischemic Heart Disease ◽

Coronary Angioplasty ◽

Protein C ◽

Ischemic Heart ◽

Soluble Fibrin ◽

Stent Restenosis ◽

History Of ◽

Thrombotic Complications ◽

D Dimer

The effect of hemostasis parameters on the development of stent restenosis / thrombosis requires further investigation. The purpose of the paper is to find out the informativeness of activators and inhibitors of the circulating blood system as markers for the development of thrombotic complications in patients with ischemic heart disease and coronary angioplasty. 92 patients (78 men and 14 women) with ischemic heart disease and coronary angioplasty were examined, of which 33 cases suffered from stent restenosis/thrombosis. The patients were simultaneously evaluated for hemostasis parameters (soluble fibrin, D-dimer, protein C, and fibrinogen). It is determined that in patients with ischemic heart disease who have undergone angioplasty in 67.4% of cases there is a significant increase in the level of soluble fibrin with subsequent significant increase in patients with a history of restenosis. It is established that the level of D-dimer in these patients is significantly lower, while in the women it is significantly lower than that of the studied men. The reaction of anticoagulant protein C in 42.4% of patients tends to decrease, taking into consideration that in 80.4% cases there is significant fibrinogenemia. Therefore, the study reveals a significant imbalance in the system of pro- and anticoagulation in this category of patients in favor of the coagulation link, and the hemostatic parameters studied in the complex can be used as informative integral markers of thrombinemia.

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APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614518 ◽

1999 ◽

Vol 81 (04) ◽

pp. 527-531 ◽

Cited By ~ 114

Author(s):

U. Kjellberg ◽

N.-E. Andersson ◽

S. Rosén ◽

L. Tengborn ◽

M. Hellgren

Keyword(s):

Factor Viii ◽

Plasminogen Activator ◽

Protein C ◽

Activated Protein C ◽

Plasminogen Activator Inhibitor ◽

Protein S ◽

Reference Level ◽

Soluble Fibrin ◽

Prothrombin Fragment ◽

D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

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Coagulogic risk factors of heart disease in the adult population of Tomsk

Systemic Hypertension ◽

10.26442/sg28986 ◽

2013 ◽

Vol 10 (4) ◽

pp. 50-54

Author(s):

A B Dobrovolsky ◽

E V Titaeva ◽

E B Yarovaya ◽

A N Storozhilova ◽

Yu V Zhernakova ◽

...

Keyword(s):

Risk Factors ◽

Protein C ◽

Clinical Characteristics ◽

Fibrinogen Level ◽

Adult Population ◽

Thrombotic Complications ◽

The Russian Federation ◽

Anticoagulant Function ◽

D Dimer ◽

Inhibition Of Thrombin

The following paper presents an analysis of fibrinogen and D-dimer levels and global index characterizing the anticoagulant function of protein C (TromboPas). 1104 people (25–64 years of age) of Tomsk adult unorganized population were examined within the framework of ECCE-RF-2012 (Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation) project. The relationships of these parameters with the main demographic and clinical characteristics were analyzed. The presence of at least one of the markers of hypercoagulability, which include fibrinogen level higher than 3,7 g/l D-dimer – 500 ng / ml, and the index of inhibition of thrombin formation in the TromboPas (PICI%) test, that islower or equal to 84%, was found in 55,44% of the patients. At the same time, in 2,72% of the surveyed population a combination of all three hypercoagulation markers was observed, whereas a combination of at least one of the mentioned markers and / or risk factors such as arterial hypertension (AH) and obesity (BMI≥30 kg/m2) was observed in 36,87% of patients. Hypercoagulation markers, hypertension and obesity were absent only in 19,47% of patients. Thus, the results suggest a high risk of thrombotic complications of cardiovascular disease (CVD) in the studied population and justify the feasibility of developing adequate methods to prevent them.

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Features of hemostasis disorders in patients with CKD VD stage and their relationship with the course of the disease

Biomedical and Biosocial Anthropology ◽

10.31393/bba36-2019-04 ◽

2020 ◽

pp. 22-26

Author(s):

O. B. Storozhuk ◽

S. V. Shevchuk ◽

L. O. Storozhuk ◽

T. V. Dovgalyuk ◽

B. G. Storozhuk

Keyword(s):

Arterial Hypertension ◽

Protein C ◽

Clinical Characteristics ◽

Statistical Processing ◽

Residual Renal Function ◽

Hemostatic System ◽

Early Predictors ◽

Almost All ◽

D Dimer

Disorders in the hemostatic system leading to the development of thrombosis are one of the main complications in patients with chronic kidney disease (CKD) of stage VD who are on program hemodialysis. The development of thrombophilic syndrome as a process of intravascular coagulation is characterized by systemic activation of procoagulative mechanisms, which are not always compensated by internal natural anticoagulant systems. The determination of early predictors of possible thrombogenesis in the studied category of patients causes significant difficulties. The goal is to study the features of hemostatic system disorders in patients with CKD VD stage who are on programmed hemodialysis, and to assess their relationship with the characteristics of the course of the disease. In 88 patients with CKD of the VD stage who are on program hemodialysis (52 men and 36 women), the features of hemostasis disorders depending on the clinical characteristics of the patients were studied. The indicators of prethrombosis (soluble fibrin (sF), fibrinogen (Fg), functionally inactive forms of prothrombin (FIFP)), postthrombosis (D-dimer (D-d)) and anticoagulation (protein C (pC)) were determined depending on gender, hemodialysis experience, age, the presence of anemia, arterial hypertension (AH) and preserved residual renal function (RRF). Statistical processing of materials was carried out using methods of variation statistics using t-student criterion. It was found that violations in the hemostatic system are detected in almost all patients. At the same time, hyperfibrinogenemia, an increase in sF concentration, a deficiency of pC, less often an accumulation of FIFP and high levels of D-d are most often observed. These disorders of hemostasis are more often found in patients with absent RRF, a longer experience of hemodialysis, the presence of arterial hypertension and are less associated with gender, age of patients and are little dependent on the degree of anemia.

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Frequency and nature of complications and hemostasis indicators in patients with ishemic artery disease, who had undergone percutaneous coronary angioplasty (based on the 18-month clinical observation)

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2019-23(2)-12 ◽

2019 ◽

Vol 23 (2) ◽

pp. 248-250

Author(s):

N. V. Storozhuk ◽

T. V. Dovgalyuk ◽

B. H. Storozhuk

Keyword(s):

Protein C ◽

Clinical Observation ◽

Statistical Processing ◽

Vascular Lesions ◽

General Group ◽

Percutaneous Coronary Angioplasty ◽

Soluble Fibrin ◽

Artery Disease ◽

Late Restenosis ◽

D Dimer

Determination of the nature, frequency and causes of restenosis/thrombosis in patients with ishemic artery disease and PKA in prospective observation is significant for the development of preventive measures depending on the clinical (comorbidity) and biochemical (state of the hemostasis system) characteristics of each patient. The goal is to study the frequency and nature of complications in patients with coronary artery disease and PKA and their hemostasis indicators. An 18-month follow-up (outpatient, inpatient and telephone mode) was performed for 91 patients, of whom 32 had a late restenosis/stent thrombosis in history (more than 6 months after stenting) and 59 – who did not have restenosis. All patients at the beginning of the study once determined the main indicators of hemostasis (soluble fibrin, D-dimer, fibrinogen and protein C). Patients followed by clinical observation did not receive anticoagulant treatment and received dual antiplatelet therapy. Statistical processing was performed using the methods of variation statistics and correlation analysis. The results of the study revealed that in the group of patients with restenosis and diabetes mellitus in the history, the risk of developing restenosis/thrombosis of the stent is twice as high as in the general group. Herewith, damage to other parts of the cardiovascular system is practically not excluded with the same frequency. The results of the study also revealed significant abnormalities in the system of hemostasis in patients with the presence of both restenosis/thrombosis and other vascular lesions. Thus, in patients with thrombotic complications, there is a sharp increase in the factor of prethrombosis – soluble fibrin, with a clear depression of the fibrinolytic linkage of hemostasis, as indicated by the low level of D-dimer. In addition, these violations of the sF/D-d ratio are associated with inhibition of the anticoagulant ability of hemostasis represented by the protein C. Consequently, the course of the disease in patients with IAD and PKA is closely related to the presence of comorbid states and hemostasis

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Coagulation and fibrinolytic potential of blood plasma in patients with stage VD CKD, treated by program hemodialysis, as the markers of thrombotic risk

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2018-22(3)-20 ◽

2018 ◽

Vol 22 (3) ◽

pp. 494-497

Author(s):

O.B. Storozhuk ◽

I.B. Seleznyova ◽

L.O. Storozhuk ◽

B.G Storozhuk ◽

T.V. Dovgalyuk ◽

...

Keyword(s):

Blood Plasma ◽

Statistical Processing ◽

High Concentration ◽

Thrombotic Risk ◽

C Protein ◽

Soluble Fibrin ◽

Thrombotic Complications ◽

Fibrinolytic Potential ◽

Protein C Activity ◽

D Dimer

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.

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Plasma D Dimer: A Useful Marker of Fibrin Breakdown in Renal Failure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646627 ◽

1989 ◽

Vol 61 (03) ◽

pp. 522-525 ◽

Cited By ~ 32

Author(s):

M P Gordge ◽

R W Faint ◽

P B Rylance ◽

H Ireland ◽

D A Lane ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Acute Renal Failure ◽

Monoclonal Antibodies ◽

Diabetic Nephropathy ◽

Renal Disease ◽

Plasma Concentrations ◽

Significant Negative Correlation ◽

Healthy Controls ◽

D Dimer

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.

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