Increased Fibrinogen Concentration Research Articles

The impact of measurement techniques and common effectors on red blood cell aggregation

Background Red blood cell aggregation is largely influenced by hematocrit and plasma protein content with aggregation increasing as hematocrit and fibrinogen increase. Aggregation measurement techniques include light-transmission or laser-backscatter, and the impact of measurement technique on aggregation measurements with respect to changes in hematocrit and plasma protein is not well understood. Objective The objective of this study was to evaluate aggregation measurement techniques with respect to common effectors of red blood cell aggregation. Methods We obtained whole blood samples from 10 healthy participants and varied hematocrit, plasma albumin, and plasma fibrinogen concentration in a sample of healthy male and female participants. We then measured red blood cell aggregation using a Myrenne Aggregometer (light-transmission aggregometer) and a Laser Optical Rotational Red Cell Analyzer (laser-backscatter aggregometer). Results For Myrenne, aggregation increased from 30% to 40% hematocrit, then declined at 50% hematocrit. Measurement in the LORRCA demonstrated an increase as hematocrit increased from 30% to 40%, and again increased at 50%, which differed from the light transmission method. Red blood cell aggregation increased with increased fibrinogen concentration, but did not change significantly as albumin concentration increased. Conclusions Red blood cell aggregation is expected to increase as hematocrit increases, but when light transmission aggregometry is used, aggregation decreases as hematocrit increases past 40%. Each measurement technique has its own set of methodological strengths and weaknesses.

Clot lysis time and thrombin generation in patients undergoing transcatheter aortic valve implantation

BackgroundAortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk.ObjectivesThe aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT).MethodsWe studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP).Results70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success.ConclusionsCLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.Graphical abstract

Association of clinical respiratory disease signs and lower respiratory tract bacterial pathogens with systemic inflammatory response in preweaning dairy calves

This study investigated the potential associations between 3 acute phase proteins (APP)-haptoglobin, serum amyloid A-and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of preweaning dairy calves. This cross-sectional study included 150 preweaning calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APP, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APP. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APP showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as Pasteurella multocida and Trueperella pyogenes in preweaning dairy calves.

Renal function and cardiovascular risk in overweight patients

Background. Currently, in most countries of the world, there is a tendency for an annual increase in the proportion of overweight people (OW). Studies performed in various age groups and devoted to the relationship of OW with the functional state of the kidneys show contradictory results.The aim: to study the functional state of the kidneys and the prevalence of risk factors for cardiovascular complications in OW, taking into account gender differences.Patients and Methods. A cross–sectional single-center study was conducted with the participation of 154 patients (73 men and 81 women) with body mass index (BMI) 25.0–29.9 kg/m2), whose average age was 53.9±12.6 years. Anthropometric and biochemical parameters were evaluated in all patients, the functional state of the kidneys (according to serum creatinine and cystatin C) was studied, and an analysis of cardiovascular risk factors was carried out.Results. Analysis of excretory renal function by cystatin C showed that in most of the examined individuals, regardless of gender, there was a decrease in eGFR to CKD stages 2 and 3a. OW among men was statistically significantly more often associated with hypertriglyceridemia (32.8 %), tachycardia (38.3 %) and atherosclerotic lesion of the carotid arteries (24.6 %). In the subgroup of women with ischemic heart disease, the average age, the content of low-density lipoproteins, the double product index, the frequency of hypercholesterolemia, dyslipidemia and hypertrophy of the left ventricle (LVH), mainly of the eccentric type, were significantly higher, and the hemoglobin content and the number of red blood cells were significantly lower. Significant correlations of eGFR with concentrations of hemoglobin and C-reactive protein, as well as with the value of the left ventricular myocardial mass index (LVMI) were found in men with ischemic heart disease. Correlations of eGFR with the levels of systolic, mean, pulse and central blood pressure, index of functional changes, LDL-C, triglycerides, hemoglobin, fibrinogen, metabolic index, as well as LVMI were found in women with ischemic heart disease. The value of LVH in women was significantly associated with the level of central blood pressure, cystatin C, LDL, hemolobin, fibrinogen, metabolic index, and eGFR. In the general sample of patients with ischemic heart disease, the content of serum cystatin C was positively correlated with LVH and inversely with eGFR calculated by cystatin C. There was a weak negative relationship between the level of central arterial pressure and eGFR by cystatin C.Conclusion. Evaluation of excretory renal function, according to cystatin C and serum creatinine, in individuals with ISM has a higher diagnostic value than evaluation using methods based on the use of serum creatinine alone. In males, the presence of OW is associated with tachycardia, hypertriglyceridemia, a significant decrease in GFR and an increase in the frequency of atherosclerotic changes in the carotid arteries. The following cardiovascular risk factors are associated in women with ischemic heart disease: old age, anemia, increased fibrinogen concentration, dyslipidemia, increased values of the double product index, metabolic index and index of functional changes, as well as hemodynamic and LVH parameters.

Prognostic value of hemostasis system indicators in patients with a traumatological profile when taking anticoagulants

Objective. To assess the state of the hemostasis system and the risk of hemorrhagic complications in patients before and after hip replacement while taking anticoagulants. Patients and methods. The study included 85 patients, 46 women (average age 62.8 ± 8.95) and 39 men (average age 55.1 ± 14.3) who were in the Clinic of Traumatology and Orthopedics of the I.I. Mechnikov NWSMU for planned hip replacement. All patients received rivaroxaban or apixaban at doses specified by Russian Clinical Guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Retrospectively, in the postoperative period, the patients were divided into 2 groups: group 1 — 78 patients (42 women and 36 men) who had no hemorrhagic complications after hip replacement, and group 2 — 7 patients (4 women and 3 men) who had hemorrhagic events in the form of hematoma in the wound area. All patients underwent laboratory tests before surgery, on the first day and on the 10th day after arthroplasty. The laboratory study included the determination of hemostasis parameters (PT in seconds, PT % activity, APTB, Fibrinogen, D-dimer), the concentration of rivaroxaban or apixaban in blood plasma, molecular genetic study of the polymorphism of the G(-455)A gene. Results. When assessing the traumatic factors of surgical intervention in patients with hemorrhagic complications, the volume of blood loss is significantly higher (p = 0,001) compared with cases of uncomplicated course. Minor hyperfibrinogenemia (Me 5,18 g/l) before surgery was detected in group 2 patients. A statistically significant increase in fibrinogen concentration (p = 0,006) occurred in patients on the background of surgery and is associated with traumatic factors of surgery. There was an increase in the concentration of fibrinogen and the level of D-dimer above the reference values on the 10th day after endoprosthesis, but no statistically significant differences were observed in both groups. The concentration of rivaroxaban in the blood was within the therapeutic interval throughout the entire observation period, and apixaban was higher than the therapeutic dose in the group of patients with complications on the 1st day after surgery, while thrombosis and bleeding were not found in patients. Conclusion. Hyperfibrinogenemia in patients in the preoperative period and after surgery may be an additional factor in the development of postoperative complications. Determination of the concentration of rivaroxaban and apixaban in blood plasma using an automatic chromogenic test allows you to evaluate their anticoagulant effect.

Characterization of the blood coagulation system in morbidly obese patients

Obesity is a complex metabolic disorder that can be followed by blood coagulation disorders, athero­sclerosis and atherothrombosis. In the present work, the levels of fibrinogen, soluble fibrin, D-dimer as well as protein C were measured in the blood plasma of 24 morbidly obese patients (the body mass index exceeds 40 kg/m2) to evaluate the risk of prothrombotic state. The study showed that near by 80% of patients had substantially increased fibrinogen concentration, 33% had increased concentration of soluble fibrin, 42% had increased level of D-dimer in blood plasma as compared to control. According to the results of individual analysis, the high level of fibrinogen and soluble fibrin while reduced protein C indicated the threat of thrombosis, which requires complex diagnostics to be identified. Therefore, simultaneous quantification of hemostatic system biomarkers in the blood plasma is the confident way to predict the risk of thrombotic complications in morbidly obese patients. Keywords: D-dimer, hemostasis, obesity, protein C, soluble fibrin, thrombosis

Hypercoagulability in COVID-19: from an unknown beginning to future therapies.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health concern and is characterized by an exaggerated inflammatory response that can lead to a large variety of clinical manifestations such as respiratory distress, sepsis, coagulopathy, and death. While it was initially considered primarily a respiratory illness, different data suggests that COVID-19 can lead to a pro-inflammatory milieu and a hypercoagulable state. Several mechanisms attempt to explain the pro-coagulant state seen in COVID-19 patients, including increased fibrinogen concentration, different receptor binding, exhausted fibrinolysis, cytokine storm, and endothelial dysfunction. Some hematological parameters, such as elevated D-dimers and other fibrinolytic products, indicate that the essence of coagulopathy is massive fibrin formation. Moreover, elevated D-dimer levels have emerged as an independent risk factor for a worse outcome, including death, indicating a potential risk for deep vein thrombosis and pulmonary thromboembolism. Prophylactic anticoagulation is recommended in all in-patients with COVID-19 to reduce the incidence of thrombosis. Those with elevated D-dimer values or with a higher risk of developing thromboembolic events should be treated with higher doses of anticoagulant. Anticoagulation may not be enough in some circumstances, highlighting the need for alternative therapies. An understanding of the complex cross-talk between inflammation and coagulopathy is necessary for developing direct appropriate interventional strategies.

Erythrocyte sedimentation: Effect of aggregation energy on gel structure during collapse.

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally explained through the formation and faster settling of large disjoint aggregates. However, many aspects of erythrocyte sedimentation conform well with the collapse of a particle gel rather than with the sedimentation of disjoint aggregates. Using experiments and cell-level numerical simulations, we systematically investigate the dependence of ESR on fibrinogen concentration and its relation to the microstructure of the gel-like erythrocyte suspension. We show that for physiological aggregation interactions, an increase in the attraction strength between cells results in a cell network with larger void spaces. This geometrical change in the network structure occurs due to anisotropic shape and deformability of erythrocytes and leads to an increased gel permeability and faster sedimentation. Our results provide a comprehensive relation between the ESR and the cell-level structure of erythrocyte suspensions and support the gel hypothesis in the interpretation of blood sedimentation.

A Clinical Study on Traumatic Pericarditis and Traumatic Reticuloperitonitis in Twelve Holstein Friesian Cattle

Background: Traumatic injury caused by swallowed sharp foreign object is one of the common conditions in dairy animal resulting into development of traumatic pericarditis (TP) and traumatic reticuloperitonitis (TRP). Under field conditions both conditions mimic the same clinical signs making it difficult to differentiate as well as render to choose ideal therapeutic management. The present study was aimed to evaluate clinical, hematobiochemical and ultrasonographic changes in cattle to clinically differentiate between TP and TRP cases. Methods: From the period of January 2020 to December 2020, total twelve Holstein Friesian cattle were investigated for TP and TRP. In the present study, six animals each suffering from TP and TRP were included along with six normal healthy animals as control. Different clinical signs, haemato-biochemical parameters and ultrasonographical findings were recorded in each group and comparative analysis was done. Result: Brisket edema, bilateral jugular vein engorgement and arched back conditions were most reported clinical signs in both the groups. Significant changes were recorded in the values of red blood cells, lymphocyte, blood urea nitrogen, creatinine and SGOT between both the groups. Significant drop in hemoglobin level was observed in TP affected group. No significant changes were observed in white blood cells, packed cell volume, monocyte counts and eosinophil counts. Significant increase in fibrinogen concentration recorded in both the groups. In ultrasonography, accumulation of anechoic fluid around heart in TP and reticular wall thickening in TRP was most consistent findings.

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)

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.

Fibrin Clot Properties in Atherosclerotic Vascular Disease: From Pathophysiology to Clinical Outcomes.

Fibrin is a major component of thrombi formed on the surface of atherosclerotic plaques. Fibrin accumulation as a consequence of local blood coagulation activation takes place inside atherosclerotic lesions and contributes to their growth. The imbalance between thrombin-mediated fibrin formation and fibrin degradation might enhance atherosclerosis in relation to inflammatory states reflected by increased fibrinogen concentrations, the key determinant of fibrin characteristics. There are large interindividual differences in fibrin clot structure and function measured in plasma-based assays and in purified fibrinogen-based systems. Several observational studies have demonstrated that subjects who tend to generate denser fibrin networks displaying impaired clot lysis are at an increased risk of developing advanced atherosclerosis and arterial thromboembolic events. Moreover, the majority of cardiovascular risk factors are also associated with unfavorably altered fibrin clot properties, with their improvement following effective therapy, in particular with aspirin, statins, and anticoagulant agents. The prothrombotic fibrin clot phenotype has been reported to have a predictive value in terms of myocardial infarction, ischemic stroke, and acute limb ischemia. This review article summarizes available data on the association of fibrin clot characteristics with atherosclerotic vascular disease and its potential practical implications.

Role of fibrinogen–erythrocyte and erythrocyte–erythrocyte adhesion on cardiovascular pathologies

Cardiovascular pathologies are the major cause of death worldwide. Erythrocyte aggregation is an indicator of cardiovascular risk, which is influenced by high plasma fibrinogen levels. Our main goals were to understand how fibrinogen–erythrocyte binding influences erythrocyte aggregation and how it constitutes a cardiovascular risk factor in essential arterial hypertension (EAH) and chronic heart failure (CHF). Differences on cell stiffness, protein-cell interaction and cell–cell adhesion forces were evaluated by AFM-based force spectroscopy with cells from 31 EAH patients, 30 CHF patients and 15 healthy blood donors. The main procedures used were previously described by us [1–3]. Results were correlated with patients’ clinical profiles. From cell–cell adhesion studies, we concluded that, upon increasing fibrinogen concentration (from 0 to 1 mg/mL), there was an increase in the work and force necessary for erythrocyte–erythrocyte detachment on EAH patients and healthy donors. Nevertheless, higher values from both parameters were obtained for EAH patients, when comparing to healthy donors, at each fibrinogen concentration [4]. Fibrinogen-erythrocyte (un)binding forces were higher in EAH and in CHF patients, when compared with the control group, despite a lower binding frequency [5,6]. Ischaemic CHF patients showed increased binding forces compared to non-ischaemic patients. A 12-month clinical follow-up shows that CHF patients with higher fibrinogen–erythrocyte binding forces, probed by AFM at the beginning of the assessment, had a significantly higher probability of being hospitalised due to cardiovascular complications, pointing out the value of AFM for clinical prognosis [5]. Erythrocyte stiffness studies revealed differences between patients and healthy donors, in terms of erythrocyte elasticity (Young’s modulus) and AFM tip penetration depth into the cells [5,6]. Erythrocytes from non-ischaemic CHF patients presented a higher average stiffness than those from the other groups (ischaemic CHF and control). Nevertheless, a significantly higher cell penetration depth at the same applied force was observed for ischaemic CHF patients [5]. In conclusion, fibrinogen promotes erythrocyte adhesion, leading to its aggregation, probably by transient simultaneous binding of the protein to two cells, bridging them. Our results may be relevant for potential future drug interventions to reduce aggregation and enhance microcirculatory flow conditions in cardiovascular patients.

Clean version: Electrospun fibrinogen scaffolds from discarded blood for wound healing

Immediate reutilization of discarded blood from surgery has not received much attention, leading to the waste of a large amount of autologous blood. We used a concentration gradient and high-voltage electrospinning technology to immediately prepare a scaffold material with high biological activity but without immunogenicity from autologous waste blood collected during surgery. Here, we fabricated and characterized a 90 mg/mL group, 110 mg/mL group, and 130 mg/mL group of fibrinogen (FBG) scaffolds. Analyses revealed that the FBG scaffolds had good film-forming properties and a clear fiber structure. in vitro cell viability experiments confirmed that the cells showed an increasing trend with increasing FBG concentrations. The cells grew well in the scaffold material and secreted more cell matrix. When human bone mesenchymal stem cells (hBMSCs) were cocultured with the scaffold material, the hBMSCs expressed osteogenic and chondrogenic biomarkers. The cellular scaffold complexes from the 3 groups were implanted in four full-thickness round wounds (Φ12 mm) on the dorsal back of each rat, the 130 mg/mL group showed a 90% reduction in wound size and the data compared to other groups were better at 14 day. These results suggest that electrospinning technology-based FBG scaffold materials derived from autologous waste blood may become an ideal tissue engineering scaffold and can be immediately used for autologous hemostasis, anti-adhesion films, and wound dressing in surgery.

Plasmatic and cell components of hemostasis in patients with serious burned wounds: studying at early period of disease

We studied coagulation parameters of severely burned patients at early period of disease (1–10 days). All patients had II–III degree burned wound, varied from 22 to 75 % total body surface area (median 40 % [35; 60]). Patients were divided into two groups: survival (35 patients, 1th group) and lethal (19 patients, 2nd group) outcomes. During burned shock (1st‑2nd day) 1th group had normal activated partial thromboplastin time, fibrinogen concentration, protein C activity, whereas in 2nd group these parameters were reliably abnormal. In both groups we noticed significant decay of antitrombin III activity and increase of D-dimer, followed by very low integrity of platelets. We found correlation between morphofunctional platelet rate and blood clotting activity. At 3rd day all patients showed significant increase of fibrinogen concentration without change of other parameters. At 10th day patients with survival outcome normalized antitrombin III activity and had particular recover of platelet integrity, patients with lethal outcomes did not have such effects. Values of D-dimer, antitrombin III and protein C activity reliably differed between the groups throughout the observation period. The decrease of antitrombin III and protein C activity in the first day after the burn is critical. Reducing the activity of antitrombin III less than 75 % is a predictor of adverse outcome.

Disturbance of Coagulative Hemostasis among Patients with Henoch-Schonlein Purpura

The Purpose: To examine the state of thrombocytic and coagulation hemostasis among patients withimmune microthrombovasculitis.Materials and Method: The study included 75 patients with immune microthrombovasculitis. Amongthem, rmen - 24 (32%), women - 51 (68%), the average age is 42.4±1.3 years. The control group consistedof 15 practically healthy persons.Results and Discussion: A study of coagulation hemostasis among patients with immunemicrothrombovasculitis showed the presence of hypercoagulation shift with the increase of fibrinogenconcentration, prothrombin index, shortening of the active partial thromboplastin time and blood clottingtime, the appearance of hybrid monolith complexes - level increase of D-dimer positive ethanol test.Conclusions: The most common clinical form of IMTV is the skin-joint form of the disease (62.2%),89.3% of patients were admitted with an acute form of the disease. Women get sick twice as often (67.3%)than men (32.7%), the highest incidence is in the young age group from 18 to 49 years (87.3%). There ishypercoagulability in case of immune microthrombovasculitis.

COVID-19 Associated Hypercoagulability: Manifestations, Mechanisms, and Management.

ABSTRACTPatients with severe coronavirus disease-2019 (COVID-19) frequently have hypercoagulability caused by the immune response to the severe acute respiratory syndrome coronavirus-2 infection. The pathophysiology of COVID-19 associated hypercoagulability is not fully understood, but characteristic changes include: increased fibrinogen concentration, increased Factor VIII activity, increased circulating von Willebrand factor, and exhausted fibrinolysis. Anticoagulant therapy improves outcomes in mechanically ventilated patients with COVID-19 and viscoelastic coagulation testing offers an opportunity to tailor anticoagulant therapy based on an individual patient's coagulation status. In this narrative review, we summarize clinical manifestations of COVID-19, mechanisms, monitoring considerations, and anticoagulant therapy. We also review unique considerations for COVID-19 patients who are on extracorporeal membrane oxygenation.

Nattokinase reduces brain infarction, fibrinogen and activated partial thromboplastin time against cerebral ischemia-reperfusion injury

Natto is a traditional Japanese food prepared from fermented soybeans. nattokinase (NK) is considered one of the most active functional ingredients in natto. The present study evaluated the neuroprotective effects of NK in gerbils subjected to focal cerebral ischemia. The gerbils were separated into four groups: control group, ischemic group and two NK groups (4 and 40 mg/day i.g. for 7 days). All gerbils were fed standard chow with or without NK prior to cerebral ischemia. Focal cerebral ischemia was induced by the occlusion of the right common carotid artery and middle cerebral artery for 60 min, followed by reperfusion. Infarct volumes were determined by 2, 3, 5-triphenyltetrazolium chloride staining. Anti-thrombotic effects of NK, such as fibrinogen, prothrombin time and activated partial thromboplastin time, were also determined. Our data showed that NK significantly reduced infarct volumes by 54-68% (p ＜ 0.01), compared to the ischemic group. Prothrombin time was not significantly different in all groups. However, low dosage NK (4 mg/day) reversed ischemic-induced increase in fibrinogen concentrations and activated partial thromboplastin time. In summary, the data indicated that oral intake of NK for 7 days may alter fibrinolytic activity and provide neuroprotective effects against focal cerebral ischemia in gerbils.

Tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in patients with symptomatic lower extremity artery disease.

Background Lower extremity artery disease (LEAD) involves progressive arterial narrowing manifested by intermittent claudication (IC). LEAD entails endothelial dysfunction and fibrinolytic disorders. In the current study, we analyze the selected parameters of the fibrinolytic system in the blood of patients with symptomatic LEAD depending on clinical parameters. Methods The test group was comprised of 80 patients with diagnosis of LEAD based on Ankle-Brachial Index (ABI) test (27 female/53 male) with an average age of 63.5±9 years. The control group included 30 healthy, non-smoking volunteers (10 female/20 male), with the median age of 56±6 years. The research material - venous blood - was sampled to determine the concentrations of tissue-type plasminogen activator (t-PA Ag), plasminogen activator inhibitor type 1 (PAI-1 Ag), D-dimer, fibrinogen, and platelet count (PLT). Results We found elevated concentrations of t-PA Ag, PAI-1 Ag, D-dimer, and fibrinogen in the plasma of subjects with symptomatic LEAD. Various stages of the Fontaine classification demonstrated a gradual, statistically significant increase in the concentrations of fibrinogen and PLT count as the disease progressed. More so, in the subgroup of LEAD patients aged ≥65 years, we observed significantly higher levels of D-dimer than in the group of younger subjects. In addition to that, the LEAD group demonstrated negative correlations of IC distance, fibrinogen concentrations, and PLT count, negative correlations of ABI at rest and concentrations of D-dimer and PLT count, as well as positive correlations between age and D-dimer levels. Conclusions High t-PA Ag concentrations in LEAD patients suggest damage to the endothelium which comprises the main source of this factor. With high PAI-1 Ag levels, inactive fibrinolytic t-PA-PAI-1 complexes are formed. Increasing fibrinogen concentrations at the subsequent stages in accordance with the Fontaine classification, indicate increasing inflammation. Moreover, heightened values of D-dimer reflect an increased secondary fibrinolysis activation as patients get older and impaired extremity vascularization, manifested by the decreasing ABI, progresses.

Tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in patients with symptomatic lower extremity artery disease.

Lower extremity artery disease (LEAD) involves progressive arterial narrowing manifested by intermittent claudication (IC). LEAD entails endothelial dysfunction and fibrinolytic disorders. In the current study, we analyze the selected parameters of the fibrinolytic system in the blood of patients with symptomatic LEAD depending on clinical parameters. The test group was comprised of 80 patients with diagnosis of LEAD based on Ankle-Brachial Index (ABI) test (27 female/53 male) with an average age of 63.5±9 years. The control group included 30 healthy, non-smoking volunteers (10 female/20 male), with the median age of 56±6 years. The research material - venous blood - was sampled to determine the concentrations of tissue-type plasminogen activator (t-PA Ag), plasminogen activator inhibitor type 1 (PAI-1 Ag), D-dimer, fibrinogen, and platelet count (PLT). We found elevated concentrations of t-PA Ag, PAI-1 Ag, D-dimer, and fibrinogen in the plasma of subjects with symptomatic LEAD. Various stages of the Fontaine classification demonstrated a gradual, statistically significant increase in the concentrations of fibrinogen and PLT count as the disease progressed. More so, in the subgroup of LEAD patients aged ≥65 years, we observed significantly higher levels of D-dimer than in the group of younger subjects. In addition to that, the LEAD group demonstrated negative correlations of IC distance, fibrinogen concentrations, and PLT count, negative correlations of ABI at rest and concentrations of D-dimer and PLT count, as well as positive correlations between age and D-dimer levels. High t-PA Ag concentrations in LEAD patients suggest damage to the endothelium which comprises the main source of this factor. With high PAI-1 Ag levels, inactive fibrinolytic t-PA-PAI-1 complexes are formed. Increasing fibrinogen concentrations at the subsequent stages in accordance with the Fontaine classification, indicate increasing inflammation. Moreover, heightened values of D-dimer reflect an increased secondary fibrinolysis activation as patients get older and impaired extremity vascularization, manifested by the decreasing ABI, progresses.

EFFECT OF CISPLATIN ON HEMOSTASIS IN EXPERIMENTAL ANIMALS

Introduction. Thrombotic complications caused by the tumor and consequences of its treatment are the leading causes of death in cancer patients. The development of a model for the pathology of hemostasis, in particular the excessive pathological clot formation, in the laboratory animals receiving antitumor agents, could help find new pharmacological methods for correcting hemostatic disorders.The purpose of the study was to study the effect of cisplatin on the blood coagulation system in mice and rats.Results. An experiment using outbred mice showed that the levels of PT-INR and aPTT were decreased and the level of fibrinogen was increased on day 10 after administration of cisplatin in the maximum tolerated dose of 10 mg/kg. A significant decrease in the PT-INR and aPTT levels was observed on day 15 after cisplatin injection only in female mice. The cisplatin injection at a dose of 4 mg/kg resulted in a decrease in the PT-INR, and aPTT levels and an increase in fibrinogen concentration on day 10. In rats, a significant decrease in the PT and aPTT levels was observed in both females and males on day 15 after cisplatin injection.Conclusion. A change in the PT and NIR, aPTT levels towards decrease and fibrinogen concentration towards increase indicates the initiation of thrombus formation.