Coagulation Kinetics Research Articles

Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood.

Normal haemostasis is an important physiological mechanism that prevents excessive bleeding during trauma, whereas the pathological thrombosis especially in diabetics leads to increased incidence of heart attacks and strokes as well as peripheral vascular events. In this work, we propose a new multiscale framework that integrates seamlessly four key components of blood clotting, namely transport of coagulation factors, coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, to model the development of thrombi under physiological and pathological conditions. We implement this framework to simulate platelet adhesion due to the exposure of tissue factor in a three-dimensional microchannel. Our results show that our model can simulate thrombin-mediated platelet activation in the flowing blood, resulting in platelet adhesion to the injury site of the channel wall. Furthermore, we simulate platelet adhesion in diabetic blood, and our results show that both the pathological alterations in the biomechanics of blood cells and changes in the amount of coagulation factors contribute to the excessive platelet adhesion and aggregation in diabetic blood. Taken together, this new framework can be used to probe synergistic mechanisms of thrombus formation under physiological and pathological conditions, and open new directions in modelling complex biological problems that involve several multiscale processes.

Effects of full-time v. part-time grazing on seasonal changes in milk coagulation properties and fatty acid composition

For this research communication our objective was to investigate to what extent milk coagulation properties and milk fatty acid (FA) composition were affected by different feeding systems, season and their interaction. Eighteen cows in total were subjected to one of three different feeding system treatments: full-time grazing or part-time grazing combined with indoor feeding of fresh grass with low or high concentrate supplementation. Milk was sampled in spring, summer and autumn. Milk coagulation time was 15.0, 19.0 and 17.7 min, coagulation dynamics 1.67, 3.41 and 1.79 min, and curd firmness 52.7, 32.4 and 47.0 mm in spring, summer and autumn, respectively. Thus, milk coagulation properties of the milk were lower during summer. There were strong seasonal effects on milk FA proportions, but there were not always changes with progressing season, or changes were different with respect to the impact of the feeding systems (system × season interaction). The milk fat was favourably rich in oleic acid, conjugated linoleic acid and α-linolenic acid and had a low n-6/n-3 fatty acid ratio in all systems. Factors like seasonal variations in grass composition and the energy balance of the cows were considered relevant for the milk FA composition. Overall, seasonal variations in milk quality were less pronounced with part-time grazing with fresh grass indoors as compared to full-time grazing without concentrate.

Integration of ultrafiltration membrane process with chemical coagulation for proficient treatment of old industrial landfill leachate

Old industrial landfill leachate (OILL) poses a significant challenge to the environment, due to the large volumes of the solid waste directly discharged into landfills which leach out by percolation during rainfall and degradation of organic waste. Various separation processes have been used for the treatment of OILL to reduce environmental pollution. The innovation in the present study is the integration of membrane ultrafiltration (UF) process with chemical coagulation to remove pollutants such as total dissolved solids (TDS), conductivity, turbidity, and color from an OILL. Various coagulants such as ferric chloride (FeCl3), activated carbon (AC) and their combinations with alum ((Al(SO4)3) and lime (Ca(OH)2) were used to optimize pretreatment by coagulation. Experiments were conducted by varying the composition of coagulants and sedimentation time. Reduction in parametric values of TDS from 3200 to 1500 mg L-1, conductivity from 5.00 to 2.34 mS cm−1, turbidity from 226 to 1 FAU, color from 2930 to 10Pt-Co, and pH from 8.23 to 4.86 were achieved by a combination of coagulation by FeCl3 and UF membrane process. Moreover, greater removal of turbidity and color of 98.7% and 99.48%, respectively were observed. Further, the coagulation kinetics were established on the basis of the pH of the supernatant liquid through modeling using SMOLUCHOWSKI equation and observed to follow first-order kinetics. FeCl3 coagulant + UF was found capable of promoting maximum removal of color and turbidity compared to the other combinations. The integrated process exhibits advantages of small footprint of equipment used, economy, environmental safety, low energy consumption, and ease of scale-up for OILL treatment with simultaneous water reclamation of at least 70%.

Platinoid effects on human plasmatic coagulation kinetics: a viscoelastic analysis.

In recent years a variety of metals (cadmium, chromium, copper, iron) have been demonstrated to modulate coagulation in vitro and in vivo. One group of metals, the platinoids, have not been assessed, and such investigation is justified given the thromboembolic phenomena associated with platinum-based chemotherapy. Thus, the goal of the present investigation was to assess the effects of carboplatin, cisplatin (platinum compounds), NAMI-A, and ruthenium chloride (ruthenium compounds) on human plasmatic coagulation. Human plasma was exposed to clinically relevant, equimolar concentrations of the aforementioned platinum and ruthenium compounds, with changes in plasmatic coagulation assessed via thrombelastography. The first series of experiments demonstrated no significant modulation of coagulation by the platinum compounds, while NAMI-A demonstrated mild hypercoagulability and ruthenium chloride exerted marked hypercoagulability. A second series of experiments utilizing a variety of specialized modifications of thrombelastography focused on ruthenium chloride revealed that this compound enhances prothrombin activation. While the hypercoagulability associated with platinum compounds in vivo do not appear to have a basis in plasmatic biochemistry, it appears that ruthenium compounds can exert procoagulant properties by enhancing the common pathway of human plasmatic coagulation. Future investigation of Ru based chemotherapeutic agents in development to assess procoagulant activity as part of evaluating their potential clinical safety is warranted.

Microkinetic coagulation assays for human and zebrafish plasma.

Coagulation assays, prothrombin time (PT), and partial thromboplastin time (PTT) are tests to measure the clotting ability of plasma and used in evaluating patients suffering from bleeding disorders. These assays require 100 μl of human plasma. In zebrafish, dilute plasma with exogenously added human fibrinogen was used. Our objective is to create a microkinetic coagulation assay for human and zebrafish plasmas using 1 μl plasma under conditions similar to PT and PTTs. Here, we developed an assay using the Take3 plate with wells holding up to 6 μl, which can be loaded in a microplate reader for measuring the absorbance of fibrin formation. In this assay, we used 1 μl of citrated zebrafish or human plasma followed by the addition of either thromboplastin or Dade ACTIN or factor X activator from Russell viper venom as an activating agent and CaCl2. We found 4 or 3 μl of the final volume of reaction was optimal. Our results showed both zebrafish and human plasmas yielded kinetic PT, kinetic PTT, and kinetic Russel's viper venom time curves similar to previously established curves using dilute plasma. This kinetic coagulation was inhibited by heparin and was reduced significantly in coagulation factor deficient plasmas. These results validated our microkinetic coagulation assays. Moreover, we derived clotting times from these kinetic curves, which were identical to human PT, PTT, and Russel's viper venom time. In conclusion, we established a microkinetic assay that could measure blood coagulation activity in models like zebrafish and human blood samples obtained from a finger prick in adults or heel prick in infants.

Longitudinal Dynamics of Coagulation and Angiogenesis Markers in Cancer Patients During and After Chemotherapy.

Hemostatic parameters have been investigated as molecular determinants of tumor progression. To analyze the dynamics of microparticle-associated tissue factor activity (MPTF), tissue factor antigen (TF-Ag), and angiopоietin-2 (ANG-2) in cancer patients before, during, and after active treatment and to explore their potential as biomarkers for metastatic occurrence and death. Blood for the analysis of MPTF, TF-Ag, ANG-2, and conventional hemostatic tests was sampled in 111 patients with various cancers at 4 consecutive visits: before first chemotherapy cycle, after 3 courses, at the sixth course, and 3 months after chemotherapy cessation. Patients were followed up until metastatic progression/death or the end of the study. MPTF did not change during chemotherapy, but increased significantly after treatment cessation. Total TF-Ag and ANG-2 decreased throughout active treatment. Significant drop of their levels was observed 3 months post therapy cessation. Progressive disease was significantly associated with higher pre-chemotherapy TF-Ag and fibrinogen. Elevated baseline levels of fibrinogen were associated with increased risk of shortened progression free survival. Cessation of chemotherapy is associated with significant change of hemostatic parameters. Pre-chemotherapy levels of TF-Ag and fibrinogen may be informative of disease state and prognosis.

Assessment of acquired activated protein C resistance with the FibWave and comparison with the ETP-based APC resistance.

Activated protein C (APC) resistance is a major risk factor of venous thrombosis which may be acquired by hormonal therapy or other causes. The FibWave, a sensitive global clot-based assay design to analyze the coagulation kinetics in plasma, may be a good candidate to assess this prothrombotic state. This study aims to assess the suitability of the FibWave to differentiate the coagulation kinetics of women on oral contraceptives. Fifty-four healthy volunteers were divided into 5 groups: men [n=13], women not using hormonal contraception [n=12], women using second [n=12] or third generation [n=12] combined oral contraceptives, and women using progestin only contraceptive [n=5]. Patients with coagulation abnormalities were also assessed [n=8]. The APC resistance was assessed on the FibWave using exogenous APC or Protac, and on the Calibrated Automated Thrombogram using the ETP-based APC resistance assay. Either in presence or in absence of APC or Protac, the FibWave was able to detect a hypercoagulable state in plasma samples. All combined oral contraceptives showed a lower FW-Max1 , FW-Max2, and FW-Min2 percentage of inhibition and a lower FW-Ttpeak ratio than the other groups. The sensitivity of the FibWave was similar to the one of the ETP-based APC resistance assay. The FibWave is able to differentiate APC resistance levels observed in women on combined oral contraceptive. The FW-Max1 , FW-Max2, and to a lesser degree FW-Min2 were identified as the most sensitive parameters with a similar performance to the ETP-based APC resistance assay.

Structural changes in cow, goat, and sheep skim milk during dynamic in vitro gastric digestion

Coagulation of milk in the stomach is the first crucial step in its digestion. Using a human gastric simulator, the dynamic gastric digestion of goat and sheep skim milk were compared with that of cow skim milk, focusing particularly on their physical characteristics. The gastric contents were analyzed for changes in dry matter and microstructure, and the extent of protein digestion. The study revealed that the skim milk from all species formed a curd within the first 15 min of gastric digestion, at which time the pH was ~6.1 to 6.3. Compared with cow skim milk, the dry matter contents of the clots formed from goat and sheep skim milk were lower and higher, respectively, which was due to the differences in their total solids and protein contents. Microstructural analysis showed that, as digestion progressed, the clot structure became more cohesive, along with a decrease in moisture content, which in turn affected the breakdown and hydrolysis of caseins by pepsin; this phenomenon was similar for milk from all species. However, the extent of moisture retained in the sheep skim milk clot appeared to be lower than those of the cow and goat skim milk clots. In addition, the relative firmness of the sheep milk clot was higher than those of the cow and goat milk clots at the end of gastric digestion. The pattern of protein hydrolysis by pepsin was similar for the milk of all species, despite the differences in the proportions of different proteins. The study provided insight into the coagulation kinetics of goat and sheep skim milk under in vitro gastric digestion conditions.

Сравнительное изучение кинетики свертывания крови и тромбообразования реологическими и электрореологическими методами.

Цель исследования: изучить механизмы формирования и тромбодинамические свойства кровяного сгустка при тромбообразовании in vitro и представить сравнительное исследование кинетики тромбообразования с помощью реологических и электрореологических методов в условиях постоянного и осциллирующего сдвигового вискозиметрического течения; оценить свертывание цельной и консервированной крови, ее вязкоупругие свой ства и влияние фибриногена и декстранов на формирование сгустка. Материалы и методы. Вязкость и удельную электропроводимость нормальной и консервированной с CPD-A1-адениновым раствором крови измеряли ротационным вискозиметром Low Shear 30 Contraves (LS30) с коаксиальными цилиндрами и копией измерительной системы MS1/1 со встроенными электродами (разработана на базе LS30) в условиях постоянного сдвигового потока и в электрическом поле. Вязкоупругие свойства нормальной цельной крови исследовали с помощью реометра Physica MCR 301 (Anton Paar, Austria) в условиях осциллирующего синусоидального потока. Результаты. Представлены результаты кинетики динамической вязкости и удельной электропроводимости консервированной крови в процессе коагуляции в условиях постоянного сдвигового потока и в электрическом поле. Исследованы вязкоупругие свойства цельной крови в условиях синусоидального осциллирующего вискозиметрического течения и представлены зависимости упругого модуля G' (storage modulus) и модуля потерь G'' (loss modulus), а также нормальных сил как функция времени при свертывании. Приводятся данные эффекта фибриногена и декстрана на упругий модуль G' и на модуль потерь G'' цельной крови в процессе коагуляции. Заключение. В условиях вискозиметрического течения при низких скоростях сдвига кинетика тромбообразования характеризуется начальным этапом постепенного увеличения кажущейся вязкости и уменьшения удельной электропроводимости крови и периодом интенсивной коагуляции, характеризирующимся экспоненциальным ростом вязкости и параллельным уменьшением удельной электропроводимости исследуемого образца. Установлено, что коагулирующая цельная кровь обладает нелинейными вязкоупругими свойствами. Кинетика образования сгустка в условиях осциллирующего вискозиметрического течения крови характеризуется увеличением упругого модуля G' и модуля потерь G'' со временем. Одновременно зарегистрирована и отрицательная нормальная сила исследуемого образца в зазоре между пластинами при постоянной толщине зазора. Повышение содержание фибриногена ускоряет коагуляцию и увеличивает значения упругого модуля G' и модуля потерь G'', а также и нормальной силы коагулирующей цельной крови. Objectives: to study the mechanisms of thrombus formation and thrombodynamic properties of a blood clot during coagulation in vitro and to present a comparative study of clot kinetics formation under conditions of steady and oscillating shear viscometric flow and at electric field by rheological and electrorheological methods; to evaluate the coagulation of whole and preserved blood, its viscoelastic properties and the effect of fi brinogen and dextrans on clot formation. Materials/ Methods. The viscosity and electrical conductivity of normal blood and blood preserved with CPD-A1-adenine solution were measured with a Low Shear 30 Contraves (LS30) rotational viscometer with coaxial cylinders and with a copy of the measuring system MS1 / 1 with builtin electrodes at a steady viscometric shear flow and in an electric field too. The viscoelastic properties of normal whole blood were investigated using a Physica MCR 301 rheometer (Anton Paar, Austria) at an oscillating sinusoidal flow. Results. Kinetics of the dynamic viscosity and electrical conductivity of preserved blood during coagulation at a steady shear flow and at electric field were obtained. The viscoelastic properties of whole blood were investigated under conditions of sinusoidal oscillating viscometric flow. The dependences of the elastic (storage) modulus G' and the loss modulus G'', as well as the normal coagulation forces as a function of time are presented. The effect of fibrinogen and dextran on the elastic modulus G' and the loss modulus G'' of whole blood during coagulation are presented. Conclusions. The kinetics of blood coagulation at low shear rates is characterized by a gradual increase of the apparent viscosity and a decrease in blood conductivity at the initial stage and an exponential increase in viscosity during intensive coagulation and a parallel decrease of conductivity too. It was established that coagulating whole blood exhibit nonlinear viscoelastic properties under conditions of sinusoidal blood flow. The kinetics of thrombus formation is characterized by increasing the elastic modulus G' (storage modulus) and the loss modulus G'' with time. The negative normal force in the gap between the plates is also registered at a constant thickness of the gap. An increase in fibrinogen content accelerates coagulation and increases the values of elastic modulus G' and loss modulus G', as well as of the normal force of coagulating whole blood.

Monte Carlo simulation of polydisperse particle deposition and coagulation dynamics in enclosed chambers

A novel Monte Carlo method is proposed to improve the computational accuracy and efficiency of Monte Carlo methods in examining the polydisperse micro- and nano-particle dynamics including deposition and coagulation processes in enclosed or vacuum chambers. In the original differentially weighted Monte Carlo (DWMC) method, the coagulation and deposition events are both treated by stochastic approaches. In the present study, the deposition event is solved by a deterministic method where a proportion of the deposited real particles inside a simulated particle is determined by a probability related to the deposition kernel. Furthermore, the operator splitting method is adopted to couple the stochastic and deterministic processes. This method is verified against both analytical solutions and experimental results for particle deposition and coagulation dynamics. The particle size distributions are obtained and the results exhibit excellent accordance with the corresponding analytical solutions and experimental results. Compared with the original DWMC method, the simulation results show that the proposed Monte Carlo method can obtain very favorable improvement in both computational accuracy and efficiency.

Analyzing coagulation dynamics during treatment of vascular malformations with thromboelastography.

Slow-flow vascular malformations are abnormal vessels that can lead to activation and consumption of coagulation factors and thrombosis, known as localized intravascular coagulopathy (LIC). Most clinical and research evidence of vascular malformation hemostasis relies on conventional coagulation studies, which may not provide a complete picture. Thromboelastograpy (TEG) is a tool that can provide real-time assessment of a patient's coagulation dynamics, and may allow for a more individualized treatment approach. We hypothesized that patients with slow-flow vascular malformations will have changes in TEG parameters peri-procedure that will help predict blood product or medication administration. Institutional Review Board approved prospective study of patients with slow-flow vascular malformations undergoing a sedated, minor procedure. TEG and conventional coagulation studies were obtained preprocedure, 15min, and when possible, at 30min after the start of the procedure. Twenty-five patients were enrolled. Median age was 15years (range 3-47years). Procedures included laser and/or sclerotherapy. There were no changes in TEG parameters from baseline to 15min or 30min. The following decreased from baseline to 15min: fibrinogen 313 to 287mg/dL (P=.001), D-dimer 1.3 to 1.1mg/L (P=.02), hemoglobin 12.8 to 11.8g/dL (P=.001), and platelet count 272000 to 256000 (P=.006). No patient had a bleeding/thrombotic complication during or within 1week postprocedure. We saw no change in TEG parameters or bleeding or clotting complications despite significant numerical changes in conventional coagulation profiles, suggesting that conventional studies may not be as useful in determining risks of bleeding or thrombotic complications peri-procedure for minor procedures.

Thromboelastography is predictive of mortality, blood transfusions, and blood loss in patients with traumatic pelvic fractures: a retrospective cohort study.

In patients with traumatic pelvic fractures, thromboelastography (TEG) is a useful tool to rapidly evaluate and identify coagulation disturbances. The purpose of this study was to examine the coagulation kinetics of patients with traumatic pelvic fractures (pelvic ring and/or acetabulum) by analyzing the TEG results at initial presentation and its relationship with mortality and blood loss. A retrospective review at our Level-1 trauma center was conducted to identify Full Trauma Team activations (FTTa) with traumatic pelvic and/or acetabular fractures who were evaluated with a TEG on initial presentation between 2012 and 2016. In-hospital mortality, product transfusion, and hemoglobin changes were analyzed. Subgroup analysis was performed based on pelvic fracture type. 141 patients with a mean age of 49.0 ± 20.8years and mean Injury Severity Score (ISS) of 25.18 ± 12.8 met inclusion criteria. PRBC transfusion occurred in 78.0% of patients; a total of 1486 blood products were transfused. A total of 65 patients (46.1%) underwent operative treatment for the pelvic injuries, and 18 patients (12.7%) required embolization. The overall in-hospital mortality rate was 14.9%. The degree of clot lysis at 30min (LY30) was significantly associated with blood loss (p < 0.0001), units of packed red blood cells (PRBCs) transfused (p < 0.0001), and mortality rate (p = 0.0002). Increased fibrinolysis evidenced by an elevated LY30 on initial TEG in patients with traumatic pelvic fractures is associated with increased blood loss, blood product transfusions, and mortality. Future studies should evaluate the clinical utility of reversing hyperfibrinolysis on initial TEG. Prognostic level III.

Solubility, Rheology, and Coagulation Kinetics of Poly-(O-Aminophenylene)Naphthoylenimide Solutions.

The effect of temperature and storage time at a constant temperature on the stability of poly-(o-aminophenylene)naphthoylenimide solutions in N-methylpyrrolidone has been analyzed using rotational rheometry. A temperature–time window beyond which an irreversible change in the viscoelastic properties of solutions due to cumulative reactions of continuous polymerization and possible intramolecular cyclization has been detected. The influence of polymer concentration and its molecular weight on the rheological properties of solutions determining the choice of methods for their processing into fibers and films has been investigated. The effect of non-solvents (water and ethanol) additives on the rheological properties of solutions and the kinetics of their coagulation has been studied. Dosed addition of non-solvent into the solution promotes a significant increase in the viscoelasticity up to gelation and phase separation. Non-solvent presence in the polymer solutions reduces the activity of the solvent, accelerates the movement of the diffusion front at coagulation, and minimizes the number of macro defects. The combination of parameters under investigation renders it possible for the first time to develop new principles modifying dopes for wet spinning into aqueous or ethanol coagulation bath and finally to obtain a heat- and fire-resistant polynaphthoylenebenzimidazole fibers.

COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness.

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy.

Self-Assembling Peptide Solution Accelerates Hemostasis.

Objective: One of the leading causes of death following traumatic injury is exsanguination. Biological material-based hemostatic agents such as fibrin, thrombin, and albumin have a high risk for causing infection. Synthetic peptide-based hemostatic agents offer an attractive alternative. The objective of this study is to explore the potential of h9e peptide as an effective hemostatic agent in both in vitro and in vivo models. Approach:In vitro blood coagulation kinetics in the presence of h9e peptide was determined as a function of gelation time using a dynamic rheometer. In vivo hemostatic effects were studied using the Wistar rat model. Results were compared to those of the commercial hemostatic product Celox™, a chitosan-based product. Adhesion of h9e peptide was evaluated using the platelet adhesion test. Biocompatibility of h9e peptide was studied in vivo using a mouse model. Results: After h9e peptide solution was mixed with blood, gelation started immediately, increased rapidly with time, and reached more than 100 Pa within 3 s. Blood coagulation strength increased as h9e peptide wt% concentration increased. In the rat model, h9e peptide solution at 5% weight concentration significantly reduced both bleeding time and blood loss, outperforming Celox. Preliminary pathological studies indicate that h9e peptide solution is biocompatible and did not have negative effects when injected subcutaneously in a mouse model. Innovation: For the first time, h9e peptide was found to have highly efficient hemostatic effects by forming nanoweb-like structures, which act as a preliminary thrombus and a surface to arrest bleeding 82% faster compared to the commercial hemostatic agent Celox. Conclusion: This study demonstrates that h9e peptide is a promising hemostatic biomaterial, not only because of its greater hemostatic effect than commercial product Celox but also because of its excellent biocompatibility based on the in vivo mouse model study.

Effect of heating milk on whey protein denaturation and cheese-making properties

The cheese-making properties of milk heated at 80 °C for different times (0–8 min), and mixtures of severely-heated milk (80 °C, 30 min) with non-heated milk were evaluated in separate experiments. In both approaches, milk pH was adjusted to 6.3, 6.7 or 7.0 before heating. Despite different distributions of denatured whey protein (WP) between casein micelle surface and serum phase, heating pH had no significant effect on cheese-making properties. The two approaches were compared by reporting the results as a function of WP denaturation rate in milk. The mixed milk approach showed a higher detrimental effect on rennet-induced coagulation kinetics and curd contraction capacity during cooking than the heated milk approach. For similar WP-denaturation rate, higher yield was obtained for the mixed milk than the heated milk as a result of the better protein retention and larger increase of cheese moisture.

Influence of fat substitution by inulin on fermentation process and physical properties of set yoghurt evaluated by an optical sensor

Inulin is a natural product with beneficial effects for human health commonly used as a source of dietary fiber, bulking agent and fat substitute in products like cheese and yoghurt. There are some confusing or contradictory results in the literature about the water holding capacity of inulin and its effect on syneresis, coagulation kinetics, rheology and texture of yoghurt, so in this study those effects were evaluated. Yoghurt fermentation tests were conducted with three fat concentrations (0.4, 1.6 and 3.6%) and three inulin levels (0, 1.6 and 3.2%). The coagulation process was monitored for the first time using simultaneously an inline light backscatter sensor, inline potentiometry and a rheometer. The increase in milk fat concentration from 0 to 3.6% delayed the start of coagulation and increased time to pH=4.8 in 11min. 3.2% of inulin addition increased yoghurt acidification rate, reduced 12min the time to pH=4.8, and increased final storage modulus and gel firmness. It was also determined that 3.2% of inulin addition increased 32% the spontaneous syneresis and had no effect on the water holding capacity of set yoghurt.

Fibrinogen Modification and Fibrin Formation in Patients with an End-Stage Renal Disease Subjected to Peritoneal Dialysis.

End-stage renal disease (ESRD) is a condition accompanied by increased inflammation, oxidative stress, risk of cardiovascular complications, and coagulopathies. The structure of fibrinogen and characteristics of fibrin from plasma samples of ESRD patients on peritoneal dialysis (PD) was investigated. Fibrinogen from ESRD patients had a higher degree of carbonylation than fibrinogen from healthy individuals. The Aα chain was the most susceptible to oxidation, followed by the Bβ chain, whereas the γ-chain was the most resistant to oxidation. Spectrofluorimetric analysis suggested a higher extent of modification of amino acid side chains in fibrinogen from ESRD patients. The tertiary structure of fibrinogen was more affected than its secondary structure. The kinetics (time and rate) of fibrinogen coagulation did not differ between the tested groups. Fibrin prepared from the isolated fibrinogen had a similar structure in both groups. Our results confirm that oxidation and structural alterations of fibrinogen occur in ESRD patients on PD, although these modifications produce no direct effect on the fibrin formation. Taking into account that some patients suffer from bleeding, whereas others develop thrombotic complications, further research on this subject is required to identify other components and processes that contribute to the outcome.

Coagulation kinetics of round-sided disk particles under simple shear flow

In this study a theoretical study is carried out on the binary collision of round-sided disks (RSD) suspended in a Newtonian fluid under a simple shear flow. RSD is composed of a disk part and a half-torus part which circumscribes the side of the disk. The diameter of the disk is fixed at 2 µm while the thickness and the half-torus size are varied so that the aspect ratio varies from 0.13 to 0.288. The liquid viscosity is changed from 0.01 to 1 Pa·s. The hydrodynamic force and van der Waals force with the Hamaker constant of 1.06 × 10−20 J are considered in tracking the position and the orientation of each particle. The Brownian motion is considered to be negligible. The collision of two particles initially separated by sufficiently a long distance is considered and the kinetic constant of coagulation is obtained by considering the presence of collision, the orientations of two particles and the flux of liquid flow. The result shows that the kinetic constant of coagulation is reduced to approximately 1/4 of the kinetic constant of non-interacting particles by the hydrodynamic interaction when the viscosity is 1 Pa·s. As collision modes, side-side and side-edge are considered. Side-side mode is found to be the dominant mode of collision for differing aspect ratio and differing viscosity of the liquid. The dominance of the side-side collision mode implies the formation of two-dimensional flocs in the shear flow.

A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function.

The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin-antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma. CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min - max: 0.10 - 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 - 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 - 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 - 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios (ρ = 0.55, p < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios (ρ = 0.71, p < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant. A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals.