Coagulation Potential Research Articles

Скринінгова коагулограма при фізіологічному перебігу вагітності

The objective: to evaluate the performance of screening coagulation tests in normal pregnancy. Materials and methods. A study of screening coagulation tests was conducted with the participation of 124 patients with normal pregnancy in terms of 12–14, 20–22, 28–30 and 37–40 weeks of gestation. The control group consisted of 82 patients who were at the pregravid stage of pregnancy planning. Coagulation tests were determined on a HELENA 2000 coagulometer. Namely, the activated partial thromboplastin time, the percentage of prothrombin by Quick and fibrinogen were examined. Results. During normal pregnancy, a dynamic, statistically significant increase in plasma fibrinogen level was determined. This indicator during full-term pregnancy differed from that of non-pregnant women by 1.8 times. During all normal pregnancies, there was no statistically significant dynamics of the activated partial thromboplastin time and the percentage of prothrombin by Quick, but there was a tendency towards these indicators increase in coagulation potential with an increase in the gestation term. Conclusion. When assessing a screening coagulation tests, pregnancy term should be taken into account first of all, rather than comparing the obtained values with reference indices for non-pregnant women. Keywords: screening coagulation tests, hemostatic system, fibrinogen level, prothrombin percentage by Quick, activated partial thromboplastin time.

Surface Water Treatment Using Tamarind Seed as Coagulants via Coagulation Process

The potential of natural coagulants is highly sought nowadays as the use of commercial coagulants, aluminum sulfate (alum) affect the environment negatively. An alternative coagulant is needed. In this study, the effectiveness of natural coagulant, the tamarind seed extract is being evaluated as a coagulant to measure the highest percentage removal of turbidity and chemical oxygen demand (COD) in the surface water. The surface water sample taken from the Sungai Perlis located in Kangar, Perlis. The sample were analysed using Jar Test Experimental works with rapid mixing speed of 120 rpm in 1 minutes, slow mixing speed of 30 rpm in 20 minutes and settling time of 1 hour. The tamarind seed is being extracted using distilled water and 1 M of sodium chloride (NaCI). Seed extract from distilled water effectively removes 99.2% of turbidity and 77.2% of COD with optimum coagulant dosage of 30 mg/L and optimal pH 5.0. While, the seed extracts from 1 M of NaCI can remove 99.4% of turbidity and 73.8% of COD with the optimum coagulant dosage of 30 mg/L and optimal pH 3.0. Hence, this study demonstrates the potentials of the seed extract of tamarind seeds using distilled water in treating the surface water.

Honey-mediated aggregation of soymilk proteins

Gluconic acid, the major organic acid in honey, is a partial hydrolysate of glucono-δ-lactone, typically used as a coagulant in preparing tofu. The present study aimed to examine the coagulation potential of five different types of honey at different concentrations, upon addition to soymilk. In some samples, aggregates formed in the upper layer at a higher honey concentration, while in others, aggregates precipitated at an intermediate honey concentration. Both phenomena were reproduced by adding different mixtures of glucono-δ-lactone and glucose, indicating that gluconic acid concentration and total sugar content of honey can trigger soymilk coagulation. Interestingly, honeys with a high concentration of gluconic acid showed a low total sugar content. Furthermore, in a trial product, the mixture of blended honey with soymilk was determined to be pasty. Our results indicate that honey can coagulate soymilk, which may provide a new and convenient method to prepare soymilk-based industrial products.

An anti‐factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A

IntroductionAcquired hemophilia A (AHA) is caused by autoantibodies against factor (F)VIII, and is characterized by severe, spontaneous bleeding, which can be life‐threatening. Emicizumab, an anti‐FIXa/FX bispecific antibody, significantly reduces bleeding events in congenital hemophilia A (HA) with and without inhibitors. The known pathophysiological mechanisms and current preclinical data in HA suggest that emicizumab could provide effective treatment for AHA, but the coagulation activities of emicizumab in these patients remain unknown. AimTo evaluate the coagulant effects of emicizumab in plasma from AHA patients. Methods and ResultsTissue factor‐triggered thrombin generation assays using normal plasma preincubated with anti‐FVIII monoclonal antibodies recognizing different epitopes demonstrated that 20 µg/mL emicizumab recovered the depressed peak levels of thrombin generation to 46% to 72%. Further studies were devised, therefore, to simulate the clinical course in AHA patients, including during the acute phase for severe bleeding requiring FVIII‐bypassing therapy, and during the subacute/chronic phase with less bleeding. Various concentrations of emicizumab were used to represent the potential changes in plasma levels based on the half‐life of the antibody (~30 days). The ex vivo addition of emicizumab to plasma samples from AHA patients (n = 16) increased peak thrombin in all cases, irrespective of the inhibitor epitope specificity. Thrombin generation at 20 and 100 µg/mL emicizumab was restored to (median) 43.9% and 92.2%, respectively. Differences were evident in some cases, however, and recovery rates appeared likely to be greater in patients with type 2 inhibitor than those with type 1. ConclusionEmicizumab improved ex vivo coagulation potential in plasma from AHA patients.

Neonatal thrombosis

Neonatal thromboembolism in pediatric patients is a rare but life-threatening condition mainly caused by combinations of at least 2 prothrombotic triggering risk factors such as the central venous lines, septic condition, and prematurity. Other risk factors include asphyxia, dehydration, liver dysfunction, inflammation, and maternal condition. Neonatal hemostatic system is different from one of the older children and adults. Coagulation proteins do not cross the placenta but are synthesized in the fetus from an early stage. In the term neonate, concentrations of several procoagulant proteins, particularly the vitamin K dependent and contact factors are reduced when compared with adults. Conversely, levels of antithrombin, heparin cofactor II and protein C and S are low at birth and fibrinolysis system is characterized by the decreased level of plasminogen and alpha-1-antiplasmin, increased tissue plasminogen activator. These features all tend to be gestational dependent and are more present in the preterm infant. Primarily in this context neonates appear to be at a higher risk of thrombosis than older children. Thrombotic complications reach their peak in the group of children born at 22–27 weeks. The role of inherited thrombophilic risk factors in neonatal VTE development is poorly defined. The presence of inherited and acquired thrombophilia in mother and newborn is also responsible for the development of thrombosis in neonates and should be considered. Thrombophilia in the mother can lead to increased coagulation potential and prethrombotic conditions during pregnancy, causing thrombotic vasculopathy at the placental level. The benefit of identifying thrombophilia in the sick preterm newborns who are in the group of risk for development of thrombotic complications may facilitate the thromboprophylaxis. Further research regarding assessment of risk factors, diagnostics and treatment strategy is required.

Using Additives for Fouling Control in a Lab-Scale MBR; Comparing the Anti-Fouling Potential of Coagulants, PAC and Bio-Film Carriers.

This study investigates the effect of different additives, such as coagulants/flocculants, adsorption agents (powdered activated carbon, PAC), and bio-film carriers, on the fouling propensity of a lab-scale membrane bio-reactor (MBR) treating synthetic municipal wastewater. The coagulation agents FO 4350 SSH, Adifloc KD 451, and PAC1 A9-M at concentrations of 10 mg/L, 10 mg/L, and 100 mg Al/L, respectively, and PAC at a concentration of 3.6 ± 0.1 g/L, exhibited the best results during their batch-mode addition to biomass samples. The optimal additives FO 4350 SSH and Adifloc KD 451 were continuously added to the bioreactor at continuous-flow addition experiments and resulted in increased membrane lifetime by 16% and 13%, respectively, suggesting that the decrease of SMPc concentration and the increase of sludge filterability is the dominant fouling reduction mechanism. On the contrary, fouling reduction was low when PAC1 A9-M and PAC were continuously added, as the membrane lifetime was increased by approximately 6%. Interestingly, the addition of bio-film carriers (at filling ratios of 40%, 50%, and 60%) did not affect SMPc concentration, sludge filterability, and trans-membrane pressure (TMP). Finally, the effluent quality was satisfactory in terms of organics and ammonia removal, as chemical oxygen demand (COD), biochemical oxygen demand (BOD)5, and NH-N concentrations were consistently below the permissible discharge limits and rarely exceeded 30, 15, and 0.9 mg/L, respectively.

FEATURES OF HEMOSTASIS SYSTEM IN WOMEN WITH THROMBOPHILIA AS ONE OF CAUSAL FACTORS FOR UNSUCCESSFUL ATTEMPTS IN EXTRACORPOREAL FERTILIZATION

Excessive activation of blood coagulation, imbalance in coagulation potential, presence of endotheliopathies, local hemorrhages and microthrombi in the area of blastocyst invasion may be common in the mechanism of implantation losses in thrombophilia. One of the ways to optimize the results of extracorporeal fertilization is the prevention of thrombotic complications. Despite the achievements of modern morphology, some issues concerning the pathogenesis of infertility and habitual miscarriage remain poorly understood. To assess the system of hemostasis in women with thrombophilia as one of the causative factors of unsuccessful attempts in extracorporeal fertilization, a study of 63 patients was conducted, which included hormonal, genetic studies, HLA−typing, ultrasonography, hysterosalpingography, determination of infectious profile and was performed depending on clinical situation. The study of the hemostasis system included the determination of total coagulation potential, analysis of primary hemostasis, fibrinolytic system, the state of intravascular hemocoagulation and antiplasmin potential of blood. The state of intravascular hemocoagulation was assessed by the concentration in blood plasma of pathological hemocoagulants, i.e. soluble complexes of fibrin monomers and fibrinogen−fibrin degradation products. The results of the study showed that in women with a thrombophilia history and unsuccessful attempts in extracorporeal fertilization, there is a pathological activation of the hemostasis system, which plays a significant role in the pathogenesis of unsuccessful fertilization attempts. In thrombophilia, a subclinical form of chronic disseminated intravascular coagulation develops, the leading link in the development of which is the activation of platelet−vascular hemostasis with subsequent involvement into the process of coagulation potential due to a decrease in the anticoagulant blood system. Key words: thrombophilia, hemostasis system, extracorporeal fertilization, infertility.

Plasma-derived factors VIIa and X mixtures (Byclot®) significantly improve impairment of coagulant potential ex vivo in plasmas from acquired hemophilia A patients

A combined product of plasma-derived factor (F)VIIa and FX (pd-FVIIa/FX; Byclot®) is currently available for the hemostatic treatment of hemophilia A and B patients with inhibitors in Japan. Limited information is available, however, on its coagulant effect in acquired hemophilia A (AHA). In the present study, we assessed the coagulant effect of pd-FVIIa/FX on impairment of coagulation potentials in AHA. The bypassing agents, pd-FVIIa/FX, recombinant FVIIa (rFVIIa), and activated prothrombin complex concentrates (aPCC) were spiked with normal plasma preincubated with anti-FVIII monoclonal antibody (AHA-model plasma), and added to plasmas from AHA patients. Clot waveform analysis (CWA) triggered by the mixture of tissue factor and ellagic acid was subsequently performed. In the AHA-model, pd-FVIIa/FX improved all of the CWA parameters in a dose-dependent manner, irrespective of epitope specificity, with significant improvements relative to rFVIIa and aPCC. The coagulant effect of pd-FVIIa/FX at 1.6µg/mL (corresponding to 120µg/kg infusion) at the maximum therapeutic dose was outside the normal range. Moreover, the addition of pd-FVIIa/FX led to a greater improvement in the coagulant potentials in AHA plasmas than those of rFVIIa and/or aPCC. These data suggest that pd-FVIIa/FX significantly improves the impaired coagulant potentials in AHA and is potentially therapeutic.

Global coagulation assays in hemophilia A: A comparison to conventional assays

BackgroundGlobal assays measure the interactions of coagulants, anticoagulants, and platelets on thrombin generation and may reflect the comprehensive coagulation potential in patients with hemophilia better than conventional assays. ObjectivesThe objectives of the current study were to investigate the value of global assays for measuring and monitoring the coagulation potential of patients with hemophilia A (HA). Patients/MethodsRotational thromboelastometry, thrombin generation assay (TGA), and activated partial thromboplastin time (APTT) clot waveform analysis were investigated in a cohort of patients with severe, moderate, and mild HA and compared with conventional assays. ResultsThe maximum velocity (MaxVel) parameter of modified thromboelastometry analysis, initiated by tissue factor and in the presence of corn trypsin inhibitor (CTI), had 92% sensitivity and 95% specificity for hemophilia diagnosis. The MaxVel also strongly correlated with factor VIII (FVIII) levels of patients with HA (r = .805, P < .0001). CTI improved the sensitivity of TGA, providing more accurate results. In particular, peak height parameter of platelet‐rich plasma samples with CTI had a sensitivity and specificity of 100% and 94%, respectively, in all patients with HA. APTT clot waveform analysis minimum value of first derivative (Min1) and minimum value of second derivative (Min2) parameters (representing speed and acceleration of clot formation, respectively) were sensitive and correlated more strongly with FVIII levels than APTT clotting times did (Min1: r = 0.786, P < 0.0001; Min2: r = 0.759, P < 0.0001; APTT: r = −0.513, P = 0.001). ConclusionsThe sensitivity and specificity of the global assays was method dependent. Correlation between clinical end points and thrombin generation might also be valuable in the era of non–factor replacement therapy.

Hyper-coagulability in obese patients accurately identified by combinations of global coagulation assay parameters

BackgroundRoutine laboratory methods are insensitive to hyper-coagulation, which may be detected by global hemostasis tests. Calibrated Automated Thrombogram (CAT) is a gold standard method to measure thrombin generation and coagulation potential. Thrombodynamics (TD) is a new global assay that monitors the spatio-temporal propagation of blood coagulation, separating initiation from amplification/propagation phases of coagulation and visualizing fibrin clot formation. AimWe investigated whether CAT and/or TD can identify hyper- and hypo-coagulable states in patients with well-characterized phenotypes and which parameters could be used as potential predictors of thrombotic risk. MethodsBlood was collected from: (1) forty healthy volunteers; (2) twelve obese patients scheduled for bariatric surgery (BMI ≥ 35 kg/m2); (3) nine patients under therapy with vitamin K-antagonists (median INR 2.7); (4) eight patients treated with low molecular weight heparins (anti-Xa activity between 0.5 and 0.7 U anti-Xa/ml); (5) ten patients with hemophilia A or B. Tissue factor induced thrombin generation was measured with CAT. Propagation of thrombin generation and clot growth from a tissue factor coated surface were monitored with TD. ResultsThrombin generation and fibrin clot formation parameters were significantly higher in obese patients compared to healthy volunteers and anticoagulated or hemophilic patients. ROC analysis of combined CAT or CAT/TD parameters (integrating thrombin generation and fibrin clot formation) demonstrated an excellent accuracy in detecting hyper-coagulability. ConclusionCombinations of CAT assay parameters and of parameters of thrombin generation burst with final fibrin clot properties allow recognizing accurately hyper-coagulable plasma and may represent predictive markers for thrombotic events.

Tough polyacrylamide-tannic acid-kaolin adhesive hydrogels for quick hemostatic application.

Adhesive hydrogels for wet and dynamic tissues are important for biomedical applications in order to withstand cyclic loading such as in the case of hemorrhaging control on the curved skins and heart tissues. However, the fabrication of hydrogels with strong mechanical properties, high adhesion strength, and hemostatic efficiency remains a big challenge. Inspired by the great adhesive behavior of mussels and Arion subfuscus, novel adhesive and hemostatic polyacrylamide-tannic acid-kaolin (PAAm-TA-KA) hydrogels were reported in this work. The hydrogels displayed high strength and toughness due to their physical and chemical crosslinking structures. The abundant catechol groups on tannic acid endow the hydrogels with strong and durable adhesion strength of up to 500kPa on porcine skin. When applied onto human skin, the hydrogels could be easily peeled off without leaving any remains and causing any damages. The kaolin nanoparticles incorporated in the PAAm-TA-KA hydrogels not only served as a physical crosslinking agent, but an activator of the blood clotting factor FXII for accelerating the formation of thrombus. The strong tissue adhesion and blood coagulant potential of the PAAm-TA-KA hydrogels imparted them high hemostatic efficiency. The free-standing, adhesive, tough, cytocompatible, and hemostatic hydrogels are highly promising for traumatic bleeding control materials.

Coagulation potential of lyophilized plasma inactivated by the Intercept method

Transfusion of blood plasma is one of the main methods of treatment of severe coagulopathy in case of massive blood loss. Material and technical support ensuring that the conditions of the cold chain are maintained is needed in order to fully supply clinics with plasma. This condition completely excludes possibility of using plasma in the field and in hard-to-reach area. Plasma lyophilization greatly simplifies solution of this task. Our study shows a change in the coagulation potential after lyophilization of the virus-inactivated by the Intercept method and quarantined freshly frozen plasma.

CHANGES IN THE HEMOSTATIC SYSTEM AGAINST THE BACKGROUND OF VARIOUS TREATMENT REGIMENS IN PATIENTS WITH ATHEROSCLEROSIS OF LOWER EXTREMITIES

About 2–3 % of the population and about 35–50 % of people over 65 years suffer from obliterating atherosclerosis of the main arteries of the lower extremities. There are many known factors that potentiate atherosclerosis. Some of them are referred to as leading, such as hyperlipoproteinemia or hypertension, others to concomitant contributing to the defeat of the arteries. According to J.S.A. Fuchs include hypertension, hypercholesterolemia and smoking as major risk factors for atherosclerosis. They are less affected by obesity, diabetes, hypertriglyceridemia, sedentary lifestyle, stress Objective of the study. The purpose of this study is to evaluate the functional status of the vascular – platelet, coagulation and fibrinolysis of the hemostasis system and their disorders using low – frequency piezoelectric thromboelastography (LPTEG) in patients with obliterating atherosclerosis of the lower extremities on the background of treatment. Materials and methods. The initial state of the hemostasis system was evaluated in 90 patients undergoing treatment for obliterating atherosclerosis of the lower extremities in the Odessa Regional Clinical Hospital and MD Odreks. All patients underwent surgery in the amount of femoral-popliteal autologous bypass grafting. Patients in the control (1st) group (45 patients) received analgesia during surgery and in the postoperative period based on epidural administration of bupivacaine, and their treatment regimen included enoxaparin 0.4 ml (40,000 anti-XA ME) 2 times a day subcutaneously into the anterolateral surface of the abdominal wall from the first postoperative day and pentoxifylline IV 200 mg twice a day for 7 days. Patients of the studied (2nd) group (45 patients) received analgesia during surgery and in the postoperative period on the basis of epidural administration of bupivacaine, also rivaroxaban 15 mg 2 times a day oraly on the first postoperative day was included in their treatment regimen. The dynamics of the state of the hemostatic system in both groups of patients with OA was evaluated using LPTEG in the first day before surgery and on the 3rd, 5th and 7th postoperative days. Results and conclusions. Before surgery and the start of treatment in patients with OA, against the background of activation of the vascular - platelet link of hemostasis, significant structural and chronometric hypercoagulation with increased thrombin generation and activation of blood fibrinolytic activity are noted. Against the background of treatment in the 1st group, platelet aggregation tends to normalize and there are significant differences compared with the indicators before treatment in the 1st group, the vascular-platelet and fibrinolytic systems did not reach normal values before 7 days, but showed a significant downward trend the degree of manifestation of their violations. Against the background of treatment of the 2nd group, significant changes were observed towards normalization in all components of the hemostatic system according to the LPTEG technique. The state of the coagulation unit of the hemostasis system in patients with OA on the 7th day of therapy does not significantly differ from the norm, it is possible to note significant shifts towards hypocoagulation within the normal range. The fibrinolytic system on the 7th day of treatment does not statistically differ from normal indicators, it has significant positive dynamics compared to 1 day. The second group revealed a statistically significant normalization of all indicators characterizing the blood coagulation potential of the blood and the aggregation ability of platelets, as well as the indicator that is responsible for changes in the fibrinolytic blood system.

Effect of storage of plasma in the presence of red blood cells and platelets: re-evaluating the shelf life of whole blood.

There is renewed interest in administering whole blood (WB) for the resuscitation of patients with bleeding trauma. The shelf life of WB was established decades ago based on the viability of red blood cells. However, plasma quality during WB storage is not established. White blood cell- and platelet-reduced WB (WB-PLT) was prepared using standard processes and compared to WB processed using a platelet-sparing WBC reduction (WB + PLT) filter. WB (± PLT) was held at 2 to 6°C for 35 days alongside control units of red blood cells (RBCs) in saline, adenine, glucose, and mannitol and liquid plasma. A series of assays explored the coagulation potential and RBC quality. While fibrinogen and α2-antiplasmin remained unaffected by storage, other factors varied between components or over time at 2 to 6°C. At 14 days factor V, factor VII, α2 -antiplasmin and free protein S antigen remained on average greater than 0.50 IU/mL or 50%, as appropriate, in WB ± PLT. Factor VIII was on average 0.49 IU/mL in WB+PLT, and 0.56 IU/mL for WB-PLT. Free protein S activity decreased significantly in all arms but remained on average greater than 40% at Day 14. Contact activation was not demonstrated before Day 14. Thrombin generation in plasma remained relatively stable to Day 35 in all arms. Clotting factor activity remained at or above a mean of 0.5 IU/mL, or 50%, at Day 14 for factor V, factor VII, factor VIII, free protein S, fibrinogen, and α2-antiplasmin in all arms. Further data on platelet function in WB+PLT is needed to inform its shelf life.

PREVALENCE OF FACTOR V LEIDEN AND PROTHROMBIN G20210A IN WOMEN WITH VON WILLEBRAND DISEASE TYPE 1

Background.Von Willebrand disease is a hereditary malfunction of the blood coagulation system caused by waveform quantitative and/or qualitative deficiency of von Willebrand factor (vWF).Aim.To evaluate the frequency of occurrence of FVLeiden and FII G20210A mutations in female patients with von Willebrand type 1 disease.Materials and methods.136 women aged from 18 to 45 years (mean 31.7 ± 0.5 years) were enrolled in a study conducted during the January 2011 — December 2017 period. Questionnaire was used to reveal hemorrhagic diathesis. Inclusion criteria were as follows: no less than 3 positive responses to questions 1–7, or 2 positive responses to questions 1–7 plus no less than 100 points of the evaluated menstrual blood loss. An independent inclusion criterion was 180 points or more in the question concerning menstrual blood loss. A mandatory inclusion criterion was the confirmation of absence of thromboembolic events in a proband and first line relatives. The study included assessment of such parameters as ristocetin-cofactor activity of von Willebrand factor (vWF:RCo), von Willebrand factor antigen (vWF:Ag), factor VIII (FVIII:C), platelet aggregation induced with ADP, ristomycin, collagen, as well as molecular-genetic assay of factor V (FVLeiden) and gene (FII G20210A) polymorphism using allele-specific polymerase chain reaction.Results.No mutations of FVLeiden and FII G20210A were revealed in 102 women with von Willebrand disease type 1. Heterozygous mutation of FVLeiden was found in 12 (8.8 %) subjects with von Willebrand disease type 1 (vWF:RCo from 27 to 47 % (mean 37.3 ± 0.8 %), vWF:Ag from 25 to 46 % (mean 37.5 ± 0.8 %), FVIII:C from 29 to 49 % (mean 44.1 ± 0.5 %). Homozygous mutation of FVLeiden was identified in 3 (2.2%) women with von Willebrand disease type 1, with vWF:RCo being 40, 43 and 45 %, vWF:Ag — 39, 44 and 42 %, FVIII:C — 47, 45 and 48 %, respectively. Heterozygous mutation FII G20210A was detected in 19 (13.9 %) subjects with von Willebrand disease type 1 (vWF:RCo from 36 to 49 % (mean 43.0 ± 0.4 %), vWF:Ag from 32 to 46 % (mean 42.2 ± 0.6 %), FVIII:C from 30 to 49 % (mean 45.1 ± 0.4 %).Conclusion.By means of diminishing the coagulation potential of the blood coagulation system, a decrease in the activity of VIII and von Willebrand factors may compensate possible negative effects associated with FVLeiden and FII G20210A gene mutations in female patients with von Willebrand type 1 disease.

Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis.

Emicizumab is a bispecific antibody to factor (F) IX/IXa and FX/FXa, which mimics FVIIIa cofactor function. Emicizumab prophylaxis significantly decreases bleeding events for patients with hemophilia A (PwHA). However, global hemostatic monitoring in emicizumab-treated PwHA remains poorly investigated. Using rotational thromboelastometry (ROTEM), we evaluated coagulation potentials of whole blood samples from seven emicizumab-treated PwHA who participated in ACE001JP/ACE002JP studies. Dose-dependent coagulation-enhancing effects of emicizumab to whole blood from PwHA mixed with an anti-FVIII C2 antibody in vitro were evident by non-activated ROTEM analysis (NATEM). The relationship between FVIII levels and NATEM parameters in PwHA not participating in the clinical trials demonstrated that CT + CFT inversely correlated with FVIII levels. These parameters were defined as NATEM-based grading of coagulation potential; 'T1' (FVIII < 1IU/dL), 'T2' (1 ≤ , < 12IU/dL) and 'T3' (12 ≤ , < 60IU/dL). Coagulation function in emicizumab-treated PwHA was determined to be 'T2' or 'T3,' and was dependent on plasma emicizumab concentration. Improvement of NATEM-based grades corresponded with significant reduction of bleeding episodes, except for target joints, and differences were due to the time to reach the coagulation-steady state in individual patients. The NATEM analysis may be useful for intra- and inter-individual evaluation of coagulation function in emicizumab-treated PwHA.

Assessment of the use of mainstream iron addition for phosphorous control on H2 S content of biogas from anaerobic digestion of sludges.

A material flux analysis on sulfur (S), phosphorus (P), aluminum (Al), and iron (Fe) was conducted for two WWTPs (Galt and Kitchener) to evaluate the potential of coagulants that are employed for phosphorus control to reduce hydrogen sulfide (H2 S) emissions in the biogas from anaerobic digestion. It was found that while the Galt WWTP receives higher concentrations of S in the raw wastewater than the Kitchener WWTP, this had only a modest impact on the speciation of S entering anaerobic digestion. At both plants, only 2%-4% of influent S entered the digesters. The presence of Fe in the sludge stream was found to cause S, that is released by volatile solid destruction and sulfate ( ) reduction, to become particulate-bound. A dosage of 1.1mg/L of Fe into the raw wastewater (11% of the Fe dosed for P control) was sufficient for sulfide (S2- ) control. Transitioning the Galt WWTP from Al to Fe dosing for P control had no significant impact on effluent P concentrations and resulted in a substantial reduction in the biogas H2 S concentration. An additional secondary benefit was an increase in the solid content of the dewatered cake. PRACTITIONER POINTS: Material flux analyses can be employed to gain insight into the fate of key elements contributing to biogas quality. The use of iron for phosphorous control can effectively control H2 S in anaerobic biogas. Conversion from Al2 (SO4 )3 to FeSO4 dosing for P control resulted in increased solid content of centrifuged biosolids.

Treatment of Water by Tamarugite Produced from White Aluminium Dross

Aluminium dross is an industrial hazardous by-product obtained in aluminium smelter plants in large quantities. Dross when subjected to water bodies decreases the groundwater pH and presence of leachable salts like NaCl and KCl in dross increases the environmental crisis (Meshram and Singh, 2018). Usually white dross has adequate metallic aluminium content that is extracted through existing pyrometallurgical and hydrometallurgical routes. Even though dross may be recycled using these technologies, large quantities of dross remains end up being land filled. This research work emphasizes on synthesis of an inorganic coagulant, tamarugite, by utilizing the aluminium content entrapped in the dross. Application of tamarugite, being a rare mineral, has not been thoroughly examined but the authors have observed the use of manufactured mineral as a coagulant in water treatment (Meshram et al. 2019). In this work, white aluminium dross is subjected to leaching with concentrated sulphuric acid. Analysis of aluminium content was being done by EDTA-EBT back titrations. Subsequently equimolar sodium hydroxide solution is added to the filtrate obtained after leaching. This solution is heated to saturation. As a solvent ethanol is employed to precipitate hydrophilic molecules of tamarugite from the saturated solution. The precipitate is decanted, washed with methanol and stored in desiccator is characterized with respect to phase, elemental, microstructural and thermal analysis. Authors have studied its coagulation potential for various types of water under different ranges of pH. Obtained sludge has been examined using EDS to understand further about the heavy metal removal. Comparison between tamarugite and various commercial coagulants has been done by Jar test. Therefore, a unique method of treating water from an industrial waste is proposed that connects solid waste management and water treatment. Development of number of such valuable products from various waste materials is an exciting aspect of industrial waste management engineering, which is the crux of sustainable development.

Platelet-Neutrophil Interplay: Insights Into Neutrophil Extracellular Trap (NET)-Driven Coagulation in Infection.

Well established for their central role in hemostasis, platelets have increasingly been appreciated as immune cells in recent years. This emerging role should not come as a surprise as the central immune cells of invertebrates, hemocytes, are able to phagocytose, secrete soluble mediators and promote coagulation of hemolymph, blurring the line between immunity and hemostasis. The undeniable evolutionary link between coagulation and immunity becomes even clearer as the role of platelets in inflammation is better understood. Platelets exert a range of immune-related functions, many of which involve an intimate interplay with leukocytes. Platelets promote leukocyte recruitment via endothelial activation and can serve as “landing pads” for leukocytes, facilitating cellular adhesion in vascular beds devoid of classic adhesion molecules. Moreover, platelets enhance leukocyte function both through direct interactions and through release of soluble mediators. Among neutrophil-platelets interactions, the modulation of neutrophil extracellular traps (NETs) is of great interest. Platelets have been shown to induce NET formation; and, in turn, NET components further regulate platelet and neutrophil function. While NETs have been shown to ensnare and kill pathogens, they also initiate coagulation via thrombin activation. In fact, increased NET formation has been associated with hypercoagulability in septic patients as well as in chronic vascular disorders. This review will delve into current knowledge of platelet-neutrophil interactions, with a focus on NET-driven coagulation, in the context of infectious diseases. A better understanding of these mechanisms will shed a light on the therapeutic potential of uncoupling immunity and coagulation through targeting of NETs.

Assessment of hemostatic disturbances in women with established rheumatoid arthritis

ObjectivesThis study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity.MethodNinety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status.ResultsThe premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients.ConclusionsOur results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.Key Points• Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis.• Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause.• Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis.• Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.