Coagulation Proteins Research Articles

Impact of alfalfa (Medicago sativa L.) galactomannan on the microstructural and physicochemical changes of milk proteins under static in-vitro digestion conditions

This paper reports on the impact of alfalfa galactomannan (AAG, 0.1, 0.5 or 1% wt.) on the colloidal changes and digestibility of sodium caseinate (NaCN) and whey protein isolate (WPI) dispersions (10% wt.) under static in-vitro digestion conditions. Static laser light scattering and confocal laser scanning microscopy-assisted assessment of the NaCN-based gastric chymes confirmed the ability of AAG to control the acid-induced protein coagulation phenomena. Contrarily, the presence of AAG in the WPI-based gastric chymes was associated with the formation of larger aggregates due to the occurrence of segregative microphase separation. The kinetic modelling of the SDS-PAGE densitometric data showed that the intragastric peptic cleavage rates were higher for caseins than whey proteins (β-lactoglobulin, α-lactalbumin). However, free amino acid (FAA) release rates did not exceed 12% under intragastric conditions, whilst notably higher release rates were achieved in the intestinal digesta (36-52%). In all cases, the FAA release rates significantly increased in the presence of AAG.

Isolation of napin from Brassica nigra seeds and coagulation activity to turbid pond water

Abstract Approach to fresh water is limited due to the growing world population and supply of clean drinking water is a global challenge. Pond water is widely used for drinking in developing countries and it has higher turbidity during rainy seasons. This purpose requires a large number of chemical coagulants that lead to a high cost of treatment. Therefore there is a need to find an economical and natural coagulant to treat turbid water. Coagulation activity is an ability of a liquid, changing to a solid or semi-solid state after sometime period of time. This study focuses on the isolation of coagulant proteins from Brassica nigra seeds responsible for water clarification. The coagulant protein (napin) was purified, quantified and identified. Napin protein was precipitated with 70% saturation of ammonium sulfate solution combined with dialysis and size-exclusion chromatography. SDS-PAGE showed that isolated napin has a molecular weight of 16 kDa. Protein quantification was done by using a NanoDrop spectrophotometer. The coagulation activity of the napin protein was measured against synthetic clay solution and turbid pond water. The coagulation assay results showed that napin protein from Brassica nigra has 85% and Moringa seeds extract has 87% coagulation activity against the synthetic clay solution after 120 min. However, the coagulation activity of napin protein against the turbid pond water was higher 85% compared to Moringa seed extract of 80%. The active coagulant napin protein would be helpful in establishing cheaper methods in scaling up the coagulant protein from the Brassica nigra seeds acting as a potential agent for water treatment.

EDCB ET AA: A Mnemonic for Resuscitating Hypothermic Patients Under Extreme Conditions

EDCB ET AA: A Mnemonic for Resuscitating Hypothermic Patients Under Extreme Conditions

Exploring Relevant mRNAs and miRNAs in Injured Urethral Tissues of Rats with High-Throughput Sequencing.

Acute urethral injuries caused by urethral endoscopy and other mechanical injuries are the main reasons for secondary infection and late urethral stricture. However, there are no studies to explore the transcriptomic changes in urethral injury and the molecular mechanism of urethral injury, which is important for the treatment and cure of urethral injury. Therefore, we used RNA-seq and sRNA-seq profiles from normal and injured urethral tissues to identify and characterize differentially expressed mRNAs and miRNAs. In total, we found 166 differentially expressed mRNAs, of which 69 were upregulated, and 97 were downregulated in injured urethral tissues. The differentially expressed mRNAs were mainly involved in the positive regulation of epithelial cell differentiation, focal adhesion, cell adhesion molecules, protein activation cascade, complement activation, complement and coagulation cascades, and chemokine-mediated signaling pathway. Additionally, we found six upregulated and four downregulated miRNAs, respectively, in the injured urethral tissues. Notably, their target genes were involved in the vascular endothelial growth factor receptor 2 binding, PI3k-Akt signaling pathway, and Notch signaling pathway. In summary, our results suggest that the cell damage response induced by mechanical injury activates the pathological immune response in a variety of ways in injured urethral tissues.

VhH anti‐thrombomodulin clone 1 inhibits TAFI activation and enhances fibrinolysis in human whole blood under flow

BackgroundThrombomodulin on endothelial cells can form a complex with thrombin. This complex has both anticoagulant properties, by activating protein C, and clot‐protective properties, by activating thrombin‐activatable fibrinolysis inhibitor (TAFI). Activated TAFI (TAFIa) inhibits plasmin‐mediated fibrinolysis. ObjectivesTAFIa inhibition is considered a potential antithrombotic strategy. So far, this goal has been pursued by developing compounds that directly inhibit TAFIa. In contrast, we here describe variable domain of heavy‐chain‐only antibody (VhH) clone 1 that inhibits TAFI activation by targeting human thrombomodulin. MethodsTwo llamas (Lama Glama) were immunized, and phage display was used to select VhH anti‐thrombomodulin (TM) clone 1. Affinity was determined with surface plasmon resonance and binding to native TM was confirmed with flow cytometry. Clone 1 was functionally assessed by competition, clot lysis, and thrombin generation assays. Last, the effect of clone 1 on tPA‐mediated fibrinolysis in human whole blood was investigated in a microfluidic fibrinolysis model. ResultsVhH anti‐TM clone 1 bound recombinant TM with a binding affinity of 1.7 ± 0.4 nM and showed binding to native TM. Clone 1 competed with thrombin for binding to TM and attenuated TAFI activation in clot lysis assays and protein C activation in thrombin generation experiments. In a microfluidic fibrinolysis model, inhibition of TM with clone 1 fully prevented TAFI activation. DiscussionWe have developed VhH anti‐TM clone 1, which inhibits TAFI activation and enhances tPA‐mediated fibrinolysis under flow. Different from agents that directly target TAFIa, our strategy should preserve direct TAFI activation via thrombin.

Proteomics Analysis in Japanese Medaka Oryzias latipes Exposed to Humic Acid Revealed Suppression of Innate Immunity and Coagulation Proteins.

Simple SummaryHumic acids are one of the main components of the natural organic matter in surface waters that give them brown color. These compounds are known to have positive effects on aquatic animals such as increased growth and stress resistance. At the same time, there is experimental evidence that humic acids, being natural xenobiotics, act as follows: they cause stress responses at the molecular level. Our aim was to study humic acid-related effects on fish by performing the proteomic analysis of the blood plasma from Japanese medaka exposed to humic acid in concentrations that can be found in natural waters. Results of the study showed that most of the plasma proteins in the exposed fish had a lower abundance compared to that of the intact fish; humic acid caused a reduction in circulating levels of complement components, coagulation factors, and their regulators.Humic acids (HA), one of the major components of dissolved organic matter, can interfere with different metabolic pathways in aquatic animals, causing various biological effects. This study aimed to provide a molecular basis for HA-related responses in fish by analyzing changes in the blood plasma proteome following short-term exposure to environmentally relevant HA concentrations using the Japanese medaka Oryzias latipes Hd-rR strain as a model organism. Proteomics data were obtained by high-performance liquid chromatography with tandem mass spectrometry analysis employing a label-free quantification approach. HA caused dysregulation of proteins involved in various biological processes, including protein folding, signaling, transport, metabolism, regulation, immune response, and coagulation. The majority of the differentially abundant proteins were down-regulated, including those involved in humoral immunity and coagulation. HA caused the decrease of the complement cascade and membrane attack complex proteins abundance, as well as proteins participating in activation and regulation of secondary hemostasis. The most pronounced suppression was observed at the highest tested HA concentration.

The Texture of Camel Milk Cheese: Effects of Milk Composition, Coagulants, and Processing Conditions.

Numerous people in African, Middle Asian, Middle Eastern, and Gulf Cooperation Council (GCC) countries highly value camel milk (CM) as it plays a vital role in their diet. The protein composition of CM as well as the structure of its casein micelles differs significantly from bovine milk (BM). Cheeses made from CM have a weak curd and soft texture compared to those made from BM. This review article presents and discusses the effect of milk protein composition, processing conditions (pasteurization and high-pressure treatment), and coagulants (camel chymosin, organic acids, plant proteases) on the quality of CM cheeses. CM cheese's weak texture is due to compositional characteristics of the milk, including low κ-casein-to-β-casein ratio (≈0.05 in CM vs. ≈0.33 in BM), large micelle size, different whey protein components, and higher proteolytic activity than BM. CM cheese texture can be improved by preheating the milk at low temperatures or by high pressure. Supplementing CM with calcium has shown inconsistent results on cheese texture, which may be due to interactions with other processing conditions. Despite their structure, CM cheeses are generally well liked in sensory studies.

SERPINE1 rs6092 Variant Is Related to Plasma Coagulation Proteins in Patients with Severe COVID-19 from a Tertiary Care Hospital.

Simple SummarySevere forms of coronavirus disease 2019 (COVID-19) are related to an alteration in the coagulation process determined by genetic factors. Variability on F5 and SERPINE1 genes has been previously reported as a risk factor for thrombosis associated with different diseases. In this study, we aimed to evaluate if two relevant variants in the F5 and SERPINE1 genes were related to the requirement of invasive mechanical ventilation in hospitalized patients with COVID-19 and/or the levels of coagulation-related proteins. We observed that patients presenting the studied variants in F5 and SERPINE1 exhibit different levels of coagulation-related proteins. Moreover, the levels of these proteins were higher among patients requiring invasive mechanical ventilation when compared to hospitalized patients with no ventilation support. This study contributes to the genetics insight regarding COVID-19 severity and the inter-individual susceptibility for a severe form of the infectious disease.An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (P-Selectin, D-dimer, P-selectin glycoprotein ligand-1, tissue plasminogen activator [tPA], plasminogen activator inhibitor-1, and Factor IX) were assessed by cytometric bead arrays in one- and two-time determinations. Accordingly, SERPINE1 rs6092, P-Selectin (GG 385 pg/mL vs. AG+AA 632 pg/mL, p = 0.0037), and tPA (GG 1858 pg/mL vs. AG+AA 2546 pg/mL, p = 0.0284) levels were different. Patients carrying the CT F5-rs6025 genotype exhibited lower levels of factor IX (CC 17,136 pg/mL vs. CT 10,247 pg/mL, p = 0.0355). Coagulation proteins were also different among IMV patients than non-IMV. PSGL-1 levels were significantly increased in the late stage of COVID-19 (>10 days). The frequencies of F5 rs6025 and SERPINE1 rs6092 variants were not different among IMV and non-IMV. The SERPINE1 rs6092 variant is related to the impaired coagulation process in patients with COVID-19 severe.

Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Растительные компоненты в продуктах для геродиетического питания

Aim. To explore some of the theoretical and practical possibilities of using vegetable powders in dairy products and beverages for older people. Materials and Methods. As raw materials, sterilized cow's milk with a mass fraction of fat of 1.5% (GOST 31450-2013), drinking water (SanPiN 3.3686-21), vegetable powders: rosehip, cranberry, baobab pulp, blueberry, sea buckthorn were used. For research, plant powders in the amount of 1.0 and 1.5% were dissolved in milk or water at a temperature of 20°C. Organoleptic parameters were determined according to GOST ISO 6658-2016. Temperature processing of experimental samples was carried out at 75; 80 and 85оС. Active acidity was determined with a testo 206-pH1 instrument. Results. The organoleptic characteristics of the samples were evaluated when combining vegetable powders in an amount of 1.0% with milk of 1.5% fat content, on the basis of which a powder from baobab pulp and a powder from rosehip fruits were selected for further research. The studies of some organoleptic, physico-chemical and technological properties of mixtures of baobab fruit powder and rosehip fruit powder with drinking water and milk with a fat mass fraction of 1.5% showed that when these powders were added, a decrease in the hydrogen index (pH) was noted, which can lead to coagulation of milk proteins during heat treatment. During thermal treatment of experimental samples with milk, the amount of vegetable powder was established, at which it is possible to apply the pasteurization temperature regime of 85оC. Conclusion. The choice is justified and the possibility and expediency of including powder from the pulp of baobab and powder from rosehip fruits in the formulations of milk-based products and beverages for herodietic nutrition is established.

Circulating Coagulation Regulator Levels After Lung Transplantation Are Associated with Acute Kidney Injury

<h3>Purpose</h3> Acute kidney injury (AKI) is a common morbidity after lung transplantation, with postoperative rates up to 65%. Since microvascular coagulation contributes to AKI in preclinical models, we hypothesized that post-reperfusion circulating levels of the coagulation regulators plasminogen activator inhibitor-1 (PAI-1), protein C, and resistin, an inhibitor of protein C, would be associated with AKI. <h3>Methods</h3> The study population included 189 recipients enrolled from 7/2017-6/2019 in the 5-center Lung Transplant Outcomes Group Acute Kidney Injury (LTOG-AKI) prospective cohort study. We used Cuzick's nonparametric test of trend to examine the associations of plasma PAI-1, resistin, and protein C levels at 6 and 24 hours post-reperfusion with AKI severity (grouping stages 2-3) over the first 7 days post-transplant. We staged AKI using Kidney Disease Improving Global Outcomes creatinine criteria. We constructed ordinal logistic regression models of the association of each biomarker with AKI stage adjusting for preoperative biomarker levels, age, gender, chronic kidney disease, and transplant diagnosis. <h3>Results</h3> AKI stage 1 occurred in 45 (24%) and stage 2-3 in 50 (26%) patients. Hospital mortality was substantially higher in stage 2-3 AKI (18% vs 2% for both no AKI and stage 1 AKI, p=0.001). Plasma PAI-1 and resistin levels at 6h were associated with AKI stage (p<0.001, p=0.001, respectively), with similar findings at 24h (p<0.001, p=0.006, respectively). Protein C levels at 6h decreased with higher AKI stage (p=0.016). Six-hour PAI-1 and protein C remained associated with AKI stage in multivariable models, while the 6h resistin-AKI stage association was attenuated, particularly by adjustment for age and preoperative resistin levels (<b>Figure 1</b>). <h3>Conclusion</h3> Plasma levels of coagulation regulators at 6h post-lung transplant are associated with AKI stage and may offer insight into pathophysiologic mechanisms contributing to high AKI rates in this population.

A CASE REPORT ON ANTENATAL MOTHER – THE HEMOPHILIA CARRIER

BACKGROUND Hemophilia is a rare bleeding disorder which is due to the deciency of a coagulation protein- the most important factor VIII.The incidence of Hemophilia- A is 1 in 5000 male births. This is a case report on an antenatal mother, who is a known case of Hemophilia-A, carrier admitted for safe connement. CASE PRESENTATION : We report a case of 37-year-old G4P2L1A1 at 38 weeks and 4 days period of gestation, a Hemophilia- A carrier was admitted for safe connement.She had family history of Hemophilia-A. All her three off-springs had Hemophilia-A. The patient was taken up for an Elective Caesarian section and she delivered an aliveterm boy baby. The baby was advised by the Paediatric Hematologist to review at the age of 6 months for factor VIII assay. In CONCLUSION: some parts of developing countries like India reducing the mortality rate of Hemophilia is still a hindrance due to the scarce availability of healthcare facilities and poor follow-up. When we diagnose Hemophilia, we should include the family history, active carrier status, clinical manifestations as well as laboratory testing. There should be equal coordination between the Obstetrician, Hematologist, Immunologist, Genetics department, and Psychologist.

Machine learning based prediction and the influence of complement – Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial

BackgroundFunctional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. Materials and methodsWe carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. Results and conclusionA prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.

Probing terahertz dynamics of multidomain protein in cell-like confinement

The development of meaningful descriptions of multidomain proteins exhibiting complex inter-domain dynamics modes is a key challenge for understanding their roles in molecular recognition and signalling processes. Here we developed a generally applicable approach for probing the low frequency collective hydration dynamics of multidomain proteins that uses terahertz spectroscopy of a protein molecule confined in a phospholipid reverse micelles environment (named Droplet THz). With the combination of normal mode analysis, we demonstrated the binding of calcium ions modulates the local inter-domain motion of the human coagulant factor VIII protein in a concentration-dependent manner. These findings highlight the Droplet THz as a valuable tool for dissecting the ultrafast dynamics of domain motion in the multidomain proteins and suggest a modulating mechanism of calcium ions on the structural flexibility and function of human coagulant proteins.

F9 mRNA splicing aberration due to a deep Intronic structural variation in a patient with moderate hemophilia B

IntroductionHemophilia B (HB) is a hereditary bleeding disorder caused by the genetic variation of the coagulation factor IX (FIX) gene (F9). Several F9 structural abnormalities, including large deletion and/or insertion, have been observed to cause HB development. However, there is limited information available on F9 deep intronic variations. In this study, we report about a novel large deletion/insertion observed in a deep region of F9 intron 1 that causes mRNA splicing abnormalities. Patient and methodsThe patient was a Japanese male diagnosed with moderate HB (FIX:C = 3.0 IU/dL). The genomic DNA of the patient was isolated from peripheral blood leukocytes. DNA sequences of F9 exons and splice donor/acceptor sites were analyzed via polymerase chain reaction and Sanger sequencing. Variant-affected F9 mRNA aberration and FIX protein production, secretion, and coagulant activity were analyzed by cell-based exon trap and splicing-competent FIX expression vector systems. ResultsA 28-bp deletion/476-bp insertion was identified in the F9 intron 1 of a patient with moderate HB. A DNA sequence identical to a part of the inverted HNRNPA1 exon 12 was inserted. Cell-based transcript analysis revealed that this large intronic deletion/insertion disrupted F9 mRNA splicing pattern, resulting in reduction of protein-coding F9 mRNA. ConclusionA novel deep intronic F9 rearrangement was identified in a Japanese patient with moderate HB. Abnormal F9 mRNA splicing pattern due to this deep intronic structural variation resulted in a reduction of protein-coding F9 mRNA, which probably caused the moderate HB phenotype.

Stoichiometric analysis reveals a unique phosphatidylserine binding site in coagulation factor X

BackgroundCellular trauma or activation exposes phosphatidylserine (PS) and the substantially more abundant phospholipid, phosphatidylethanolamine (PE), on the outer layer of the plasma membrane, thereby allowing binding of many blood clotting proteins. We previously proposed the Anything But Choline (ABC) hypothesis to explain how PS and PE synergize to support binding of clotting proteins with gamma‐carboxyglutamate (Gla)‐rich domains, which posited that each Gla domain binds to a limited number of PS molecules and multiple PE molecules. However, the minimal number of PS molecules required to stably bind a Gla‐domain–containing blood clotting protein in the presence of excess PE was unknown. ObjectiveTo test the ABC hypothesis for factor X by determining the threshold binding requirement of PS molecules under conditions of PS–PE synergy. MethodsWe used surface plasmon resonance to investigate the stoichiometry of factor X binding to nanoscale membrane bilayers (Nanodiscs) of varying phospholipid composition. Results and ConclusionsWe quantified 1.05 ± 0.2 PS molecules per bound factor X molecule in Nanodiscs containing a mixture of 10% PS, 60% PE, and 30% phosphatidylcholine. Hence, there appears to be one truly PS‐specific binding site per Gla domain, while the remaining membrane binding interactions can be satisfied by PE.

Changes in Whey Proteome between Mediterranean and Murrah Buffalo Colostrum and Mature Milk Reflect Their Pharmaceutical and Medicinal Value.

Milk represents an integrated meal for newborns; its whey protein is rich in many health beneficial components and proteins. The current study aimed to investigate the differences between colostrum and mature milk from Mediterranean and Murrah buffaloes using labeled proteomics and bioinformatics tools. In the current work, LC-MS/MS analysis led to identification of 780 proteins from which 638 were shared among three independent TMT experiments. The significantly changed proteins between the studied types were analyzed using gene ontology enrichment and KEGG pathways, and their interactions were generated using STRING database. Results indicated that immunological, muscular development and function, blood coagulation, heme related, neuronal, translation, metabolic process, and binding proteins were the main terms. Overall, colostrum showed higher levels of immunoglobulins, myosins, actin, neurofascin, syntaxins, thyroglobulins, and RNA-binding proteins, reflecting its importance in the development and activity of immunological, muscular, cardiac, neuronal, and thyroid systems, while lactoferrin and ferritin were increased in mature milk, highlighting its role in iron storage and hemoglobin formation.

Hemostatic effects of therapeutic plasma exchange: A concise review.

Therapeutic plasma exchange (TPE) alters the hemostatic balance. Contributing to TPE's hemostatic effects is the mechanical processing of blood in the extracorporeal circuit, circuit anticoagulant, type of replacement fluid, TPE schedule and number of procedures, TPE timing relative to invasive procedures, and removal of nontargeted components such as platelets, coagulation proteins, and cytokines. Although TPE's hemostatic effects are well established, how it impacts the bleeding risk is not clearly understood. In this concise review, we describe the effects of the above TPE-related factors on hemostatic balance, present data on the effects of TPE on blood hemostasis, including its effects on platelet counts and clotting assays, and review the literature on the impact of TPE-induced hemostatic changes on TPE-associated bleeding events. Finally, we discuss risk factors associated with bleeding during TPE and review the literature on TPE-associated hemostatic effects in the pediatric population.

Evaluation of efficacy and safety of rivaroxaban combined with aspirin in patients with chronic coronary artery disease: A protocol for systematic review and meta-analysis.

Background:Coronary artery disease (CAD) is among the main causes of morbidities and mortalities globally. It is also considered to be an outcome of acute thrombotic events which entail activating platelets as well as coagulation proteins. In particular, rivaroxaban along with aspirin have been considered to reduce thrombotic events. However, they are yet to be evaluated by combining with or putting them against each other in patients experiencing CAD. This study intends to carry out an evaluation of whether combining rivaroxaben with aspirin will be effective and safe in treating patients experiencing chronic CAD.Methods and analysis:We intend to search information from the following databases: MEDLINE, EMBASE, Web of Science, Cochrane library, WanFang, and China National Knowledge Infrastructure. In the search, we intend to regard randomized control trials written in either English or Chinese and only those published until December 2021, as well as only those that have assessed the effectiveness and safety of combining rivaroxaban and aspirin in treating patients suffering from chronic CAD. We intend to accompany the study identification with searching or relevant reference lists as well as citations. We will also contact respective authors to provide additional information or data were needful. From the search, we will collate all citations identified and remove all duplicates. Similarly, 2 independent authors will screen all the titles and abstracts and assess them against the inclusion criteria for the study. Only selected studies will be included for critical appraisal, extraction of data, and synthesis. We will then conduct statistical analyses by utilizing a random-effect model.Ethics and dissemination:This study does not require ethical approval as the findings will be published in a peer-review journal.Registration number:10.17605/OSF.IO/WBGE4

Inhibition of caspase-1-mediated inflammasome activation reduced blood coagulation in cerebrospinal fluid after subarachnoid haemorrhage.

SummaryBackgroundNeuroinflammation and blood coagulation responses in cerebrospinal fluid (CSF) contribute to the poor outcome associated with subarachnoid haemorrhage (SAH). We explored the role of caspase-1-mediated inflammasome activation on extrinsic blood coagulation in CSF after SAH.MethodsPost-SAH proteomic changes and correlation between caspase-1 with extrinsic coagulation factors in human CSF after SAH were analysed. Time course and cell localisation of brain inflammasome and extrinsic coagulation proteins after SAH were explored in a rat SAH model. Pharmacological inhibition of caspase-1 via VX-765 was used to explore the role of caspase-1 in blood clearance and CSF circulation after SAH in rats. Primary astrocytes were used to evaluate the role of caspase-1 in haemoglobin-induced pyroptosis and tissue factor (TF) production/release.FindingsNeuroinflammation and blood coagulation activated after SAH in human CSF. The caspase-1 levels significantly correlated with the extrinsic coagulation factors. The activated caspase-1 and extrinsic coagulation initiator TF was increased on astrocytes after SAH in rats. VX-765 attenuated neurological deficits by accelerating CSF circulation and blood clearance through inhibiting pyroptotic neuroinflammation and TF-induced fibrin deposition in the short-term, and improved learning and memory capacity by preventing hippocampal neuronal loss and hydrocephalus in the long-term after SAH in rats. VX-765 reduced haemoglobin-induced pyroptosis and TF production/release in primary astrocytes.InterpretationInhibition of caspase-1 by VX-765 appears to be a potential treatment against neuroinflammation and blood coagulation in CSF after SAH.FundingThis study was supported by National Institutes of Health of United States of America, and National Natural Science Foundation of China.