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Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results in lasting neurological deficits and an increased risk of autism. The impact of blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects of blood after neurovascular damage in preterm infants. Here, we show that fibrinogen, a blood-clotting protein, plays a central role in impairing neonatal cerebellar development. Longitudinal MRI of preterm infants revealed that cerebellar bleeds were the most critical factor associated with poor cerebellar growth. Using inflammatory and hemorrhagic mouse models of neonatal cerebellar injury, we found that fibrinogen increased innate immune activation and impeded neurogenesis in the developing cerebellum. Fibrinogen inhibited sonic hedgehog (SHH) signaling, the main mitogenic pathway in cerebellar granule neuron progenitors (CGNPs), and was sufficient to disrupt cerebellar growth. Genetic fibrinogen depletion attenuated neuroinflammation, promoted CGNP proliferation, and preserved normal cerebellar development after neurovascular damage. Our findings suggest that fibrinogen alters the balance of SHH signaling in the neurovascular niche and may serve as a therapeutic target to mitigate developmental brain injury after CNS hemorrhage.

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

Introduction: Anticoagulants have been discovered and developed over past 100 years. At the beginning unfractionated heparin found its applications, just later to fade into the background of newer and more effective drugs. Patients have been treated with more and more progressive medications -- Low-Molecule-Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and Novel Oral Anticoagulants (NOAC). All of them have many indications but most importantly they are used in prophylaxis and treatment of venous thromboembolism (VTE). Scientists and physicians have been working for years to come up with the perfect drug that has fewer contraindications, side effects and doesn't need continuous anticoagulant monitoring. As for today, deemed a turning point in anticoagulant therapy are inhibitors of factor XI. It is a ground-breaking innovation as it ensures high prevention of thrombotic episodes and guarantees intact physiological hemostasis. Current State of Knowledge: The coagulation cascade and molecules part taking in that have been discovered and described extensively and in detail. Historically, the demand for anticoagulants was always a burning subject. A huge progress has been made in the last one hundred years. Treatment which clinicians are using currently is a combination of drugs used in the past and the novel forms. Unfractionated heparin is the oldest out of all and despite its simple action mechanism and adverse effects, is still a requested drug. Its lighter form, low-molecule-weight-heparin (LMWH) is an enhancement to the previous treatment due to its higher bioavailability and fewer side effects. Vitamin K antagonists (VKAs) are widely spread in medical environment thanks to their expanded mechanism of action, oral administration and reversibility of their overdose, as well as their well-developed anti-side effect therapy. Novel Oral Anticoagulants (NOACs) have been introduced to the market about 10 years ago. In spite of NOACs short period of clinical use, they were a huge change to the previous treating methods. No need of constant checking the coagulation times was a great convenience to both patients and doctors. Currently, the newest innovation in anticoagulant therapy are inhibitors of factor XI. Even though it still undergoes clinical trials, the outcome is promising for the future. Summary: The present article discusses history of anticoagulant drugs, their mechanism of action and usage but also focuses on the recent perspectives and developments as new anticoagulant drugs are being put to the test in therapeutic trials. The review underlines the importance and a big demand for improvements in old therapeutic methods and exploring the new, more suitable ones. [ABSTRACT FROM AUTHOR]

Background: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. Methods: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. Results: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. Conclusions: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker. [ABSTRACT FROM AUTHOR]

Background Aims Conclusions Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure.Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients.This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management. [ABSTRACT FROM AUTHOR]

Objective Design Setting Animals Methods Results Conclusion To compare the accuracy of a point‐of‐care coagulation analyzer (POCCA) with a reference laboratory coagulation analyzer (LabCA) and to evaluate for confounding factors that could alter the performance of the POCCA.Prospective, observational study.Two university veterinary teaching hospitals.Forty‐three client‐owned dogs undergoing coagulation testing between April 2020 and June 2021.Samples were obtained from dogs undergoing coagulation testing as part of a diagnostic workup. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured on the POCCA and on the LabCA. PCV, platelet count, total plasma protein, hyperbilirubinemia, hemolysis, lipemia, and autoagglutination were recorded.Moderate correlation was seen for PT and strong correlation was seen for aPTT between the POCCA and the LabCA (PT: 0.59, P < 0.0001; aPTT: 0.71, P < 0.0001). The POCCA results were consistent with normal or hypocoagulable samples for 30 of 38 PT and 33 of 37 aPTT results, as identified by the LabCA. Samples with PCV of 30%–55% were moderately correlated (PT: 0.63, P = 0.0004; aPTT: 0.63, P = 0.0003), but those outside that range were more likely to register an error message on the POCCA or provide disparate results. When hemolysis was present, there was a weak correlation between the POCCA and the LabCA for PT (rho: 0.38 [95% confidence interval: 0.19–0.76], P = 0.18) and a strong correlation for aPTT (rho: 0.86 [95% confidence interval: 0.62–0.95], P < 0.0001). Samples with hyperbilirubinemia were strongly correlated for PT (0.97, P = 0.002) but not for aPTT. Lipemia and autoagglutination were not observed.There was an acceptable correlation in patients with PCV within the manufacturer's recommended reference range; however, measurements on samples with PCV outside the reference range were inconsistent with the LabCA. Caution should be used when using the POCCA in patients with coagulopathy and anemia or other potential confounders. [ABSTRACT FROM AUTHOR]

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neoangiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, nonselective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors that lead to hypercoagulation is considered paramount. Hyperglycemia is a well-known prothrombotic factor, a fact that has received little attention in neuro-oncology. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time and activated partial thromboplastin time [aPTT]) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients who were operated on in 2 hospitals: Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia; and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ = –0.379; P = 0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ = –0.211; P = 0.0082). No connection was found between HbA1c and D-dimers or prothrombin time. Our results suggest that patients with hyperglycemia, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help to elucidate the vicious connection between glioblastomas and coagulation and to combat this deadly disease. [ABSTRACT FROM AUTHOR]

Harmonization of the laboratory total testing process (TTP) is critical to improving patient outcome. In 2016, an EFLM survey on the harmonization of TTP underlined the serious shortcomings pertaining to the post-analytical phase. In 2023, the WG-H conducted a new survey aiming to update information in the 2016 harmonization report in order to ascertain whether countries that had declared they were keen to adopt SI units had continued with this program, the aim being to verify the state-of art in harmonization units in areas of laboratory medicine not included in the previous survey. Questionnaires were distributed to the Presidents and National Representatives of EFLM Full Member Societies and EFLM affiliate Members. The survey questions were grouped into three categories: measurement units, reference intervals, and nomenclature/terminology, and results were evaluated using Survey Monkey software and Excel. A total of 123 questionnaires from 31 countries were analyzed. A trend (+19.3 %) was observed toward a wider use of SI units for general clinical biochemistry parameters. The results for tests not included in the 2016 survey (i.e., endocrinology diagnostics and coagulation panels), demonstrated that for reports on hormones, responses were satisfactory, 70–90 % of the responders adopting the recommended units, whereas for coagulation test panels, a serious lack of harmonization was found, "seconds", which are inaccurate and not recommended, being widely used units (91 %). The findings made in the 2023 survey demonstrated a progressive, albeit slow, improvement in harmonization reports. However, further efforts at improvement are mandatory. [ABSTRACT FROM AUTHOR]

This document discusses the stability of coagulation assays in plasma samples. The study found that the stability of coagulation assays varied depending on the specific assay and storage conditions. For example, prothrombin time (PT) and fibrinogen (Fbg) were stable for 24 hours at room temperature (RT) only in plasma aliquots, while activated partial thromboplastin time (aPTT) showed a clinically significant increase after 4 hours at RT. The study also found that storage at 4-8 °C should be avoided for PT and aPTT testing. Overall, the results suggest that coagulation samples have longer stability than current guidelines indicate, with the exception of aPTT. [Extracted from the article]

The marine environment presents challenges for wound healing in cetaceans, despite their remarkable recovery abilities with minimal infections or complications. However, the molecular mechanism underlying this efficient wound healing remains underexplored. To better understand the molecular mechanisms behind wound healing in cetaceans, we investigated the evolutionary patterns of 37 wound healing‐related genes in representative mammals. We found wound healing‐related genes experience adaptive evolution in cetaceans: (1) Three extrinsic coagulation pathway‐related genes—tissue factor (F3), coagulation factor VII (F7), and coagulation factor X (F10)—are subject to positive selection in cetaceans, which might promote efficient hemostasis after injury; positive selection in transforming growth factor‐beta 2 (TGF‐β2), transforming growth factor‐beta 3 (TGF‐β3), and platelet‐derived growth factor D (PDGFD), which play immunological roles in wound healing, may help cetaceans enhance inflammatory response and tissue debridement. (2) Coagulation factor XII (F12) is the initiation factor in the intrinsic coagulation pathway. It had a premature stop codon mutation and was subjected to selective stress relaxation in cetaceans, suggesting that the early termination of F12 may help cetaceans avoid the risk of vascular blockage during diving. (3) Fibrinogen alpha chain (FGA) and FIII, which were detected to contain the specific amino acid substitutions in marine mammals, indicating similar evolutionary mechanisms might exist among marine mammals to maintain strong wound‐healing ability. Thus, our research provides further impetus to study the evolution of the wound healing system in cetaceans and other marine mammals, extending knowledge of preventing coagulation disorder and atherosclerosis in humans. [ABSTRACT FROM AUTHOR]

Objective: A coagulation factor called fibrinogen is produced by the liver and is proteolyzed by thrombin to become fibrin. The latest studies have revealed that fibrin(ogen) palys an essential role in the regulation of cardiovascular disease. Understanding the relationship and mechanism between fibrin(ogen) and cardiovascular disease is of great significance for maintaining overall health. The objective of this review is to discuss the specific involvement and underlying mechanisms of fibrin(ogen) in cardiovascular disease. Methods: A review was conducted using the PubMed database to identify and analyze the emerging role of fibrinogen in cardiovascular disease. Results: The literature review revealed that fibrin(ogen) plays a pivotal role in maintaining cardiovascular disease and are involved in the pathogenesis of cardiovascular disease. Fibrin(ogen) mainly influence various pathophysiological processes, such as participating in thrombosis formation, stimulating the inflammatory response, and other molecular pathways. Conclusion: This review focuses on the involvement of fibrin(ogen) in cardiovascular disease, with a particular emphasis on the main functions and underlying mechanisms by which fibrin(ogen) influence the pathogenesis and progression of these conditions. This review underscores the potential of fibrin(ogen) as therapeutic targets in managing cardiovascular disease. [ABSTRACT FROM AUTHOR]

Canine parvoviral enteritis remains one of the commonest causes of death in young dogs. This study aimed to determine serum total antioxidant capacity (TAC) and total oxidant status (TOS) levels in dogs with canine parvoviral enteritis (CPV) and reveal the risk factors of DIC formation. Thirty dogs were included in the study. The dogs were divided into two groups; the first group consisted of 20 dogs diagnosed with CPV (study group) and the other group consisted of 10 healthy dogs aged 0-12 months (control group). The mean TAC value was 0.354±0.018 mmol Trolox equiv./L in the control group and 0.295±0.007 mmol Trolox equiv./L in the study group. The mean TOS level was determined as 6.539±0.154 µmol H2O2/L in the control group and 7.934±0.364 µmol H2O2/L in the study group. The mean nitric oxide (NO) concentration was 18.613±0.856 µmol/L in the control group and 21.781±0.913 µmol/L in the study group. D-dimer levels were found to be 0.170±0.070 mg/dL in the control group and 2.585±0.584 mg/dL in the study group. As a result, it was demonstrated that it is essential to consider that oxidative stress increases and antioxidant capacity decreases in dogs with CPV and that disseminated intravascular coagulation (DIC) may develop in dogs with CPV. It is thought that considering oxidative stress and DIC during the treatment may contribute positively to prognosis and survival. [ABSTRACT FROM AUTHOR]

This work was designed to evaluate maximum platelet contractile force and thrombus area before and after cardiopulmonary bypass (CPB) in pediatric patients having congenital heart disease (CHD) surgery using a microfluidic device. A prospective cohort study was designed. The work took place at an academic medical center. Twenty pediatric CHD patients ≤8 years of age with expected CPB time >30 minutes were enrolled. None. Blood was collected at baseline and post-CPB. Maximum platelet contractile force and thrombus area were evaluated in vitro using a microfluidic device (ATLAS PST). Post-CPB samples were supplemented with recombinant von Willebrand factor (rVWF) to explore the impact on contractile force and thrombus area. At baseline, the maximum thrombus area was 0.06 (0.05, 0.07), and the maximum force was 123.3 nN (68.4, 299.5). Linear mixed-effects regression models showed that the maximum thrombus area was larger post-CPB and post-CPB + rVWF compared with pre-CPB (estimated coefficient [Est] = 0.04, p = 0.002; Est = 0.09, p < 0.001, respectively). The maximum thrombus area was also larger post-CPB + rVWF compared with post-CPB (Est = 0.04, p = 0.001). Force was higher post-CPB + rVWF compared with pre-CPB (Est = 173.32, p = 0.044). In pediatric CHD patients, microfluidic testing demonstrated that platelet thrombus area increased slightly after CPB, while platelet contractile force did not change. In vitro addition of rVWF further increased thrombus area, suggesting augmentation of primary hemostasis. Microfluidic assessment of platelet contractile force and thrombus area in pediatric CHD patients appears feasible and can demonstrate changes after CPB. Further studies are needed to determine its accuracy, clinical utility, and normal values for pediatric patients. [ABSTRACT FROM AUTHOR]

This study investigates the use of the nettle leaves (Urtica dioica) extract as a novel source of a protease for clotting dromedary milk. The aim of this work is to study the impact of heat treatment (60 and 70 °C during 30 min) applied to dromedary milk before coagulation process and extracting pH of Urtica dioica (pH 4 and pH 6) on the macroscopic and molecular properties of dromedary milk gel. Enzymatic coagulation was monitored by turbiscan, rheology and fluorescence spectroscopy measurements. Turbiscan results indicated a sedimentation phenomenon for milk heated at 70 °C, while for milk heated at 60 °C, particle migration showed flocculation. The results obtained by rheology showed an increase in G′ and G′′ moduli for all milk gel samples as a function of time, reflecting the formation of casein bonds and the hydrolysis of additional bonds. Fluorescence intensity of milk gel fluorophores exhibited changes with a similar shape during enzymatic coagulation, indicating variation in the structure of casein micelle integrity. Principal component analysis applied to fluorescence spectroscopy data showed a clear discrimination between heated and raw milk coagulated by Urtica dioica extract at pH 4 from those coagulated by extract at pH 6 and camel chymosin. Finally, it was found that the heat treatment of dromedary milk at 60 °C during 30 min and coagulation with Urtica dioica extract at pH 4 generated properties of the milk gel closer to that of chymosin. [ABSTRACT FROM AUTHOR]

In this study, ferrate was synthesized and applied as a green and multi-purpose agent for simultaneous coagulation, oxidation, and disinfection to remove turbidity, TSS, COD, UV254, and pathogens from Hau River water. Statistical analyses showed that pH, ferrate dose, and their interaction significantly affected the removals of turbidity, COD, UV254, and coliforms. While ferrate provided the highest removal efficiencies of disinfection, COD, and UV254 at low pH (pH 5), suggesting its role in the oxidation process, it is necessary to raise pH (pH 9) to achieve high turbidity removal via sweep flocculation. The single use of ferrate at pH 5 and 5 mgFe/L resulted in the removal efficiencies of 75% of turbidity, 92% of COD, and 100% of coliforms. The combination of ferrate with alum (2.5 mgFe/L, 8 mgAl/L, and pH 7) followed by sand filtration achieved 95% removal of COD and 100% removal of both turbidity and coliform. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a prevalent complication among patients with cancer, contributing significantly to morbidity and mortality. However, the relationship between VTE-related genes (VRGs) and their potential impact on prognosis, immune response, and therapeutic targets in various cancer types remains unclear. Based on the coagulation and complement pathways, we identified hub VRGs that play a role in regulating the immune response in cancer. Specifically, coagulation factor III (F3), plasminogen activator (PLAT) and complement C1s (C1S) were identified as genes that exhibit high expression levels, positively correlating with tumor stemness and copy number variations, while inversely correlating with methylation levels, in particular cancer types. Pan-cancer survival analysis revealed detrimental effects of these VRGs in several cancer types, notably in glioblastoma and lower grade glioma (GMBLGG). Further analysis using receiver operating characteristic (ROC) curves demonstrated a high accuracy of F3, PLAT and C1S in predicting outcomes in GBMLGG, with area under the curve (AUC) values ranging from 0.78 to 0.9. Validation of the prognostic value of these three genes in GMBLGG was conducted using an independent Gene Expression Omnibus (GEO) dataset. Additionally, gene–drug association analysis identified ciclosporin, ouabain and 6- mercaptopurine, which all exhibit immunosuppressive properties, as potential therapeutic options for tumor patients exhibiting high F3, PLAT or C1S expression, respectively. In summary, our findings provide a bioinformatics perspective on VRGs in pan-cancer, highlighting the pivotal roles of F3, PLAT and C1S, which could potentially be therapeutically exploited and targeted in several cancers, especially in GBMLGG. [ABSTRACT FROM AUTHOR]

Background: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. Methods: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. Results: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. Conclusions: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: Several pathological conditions trigger the formation of microvesicles (MVs), including infectious diseases such as COVID-19. The shedding of MVs increases the levels of inflammatory factors (e.g., interleukin-6; IL-6) and ultimately leads to an inflammatory cascade response, while also increasing the procoagulant response. The current study aimed to evaluate the level of circulating MVs and their procoagulant activity as well as the serum level of IL-6 in patients with COVID-19 and healthy controls. In this case-control study, 65 patients with COVID-19 and 30 healthy individuals were sampled after obtaining written informed consent. MVs counting was measured using conjugated CD61, CD45, CD235a, and Annexin-V antibodies. Additionally, the procoagulant activity of MVs and the IL-6 level were estimated using enzyme-linked immunosorbent assay (ELISA). Results: The majority of MVs were platelet-derived MVs (PMVs). Patients with COVID-19 had significantly higher levels of MVs, procoagulant MVs, and IL-6 compared to healthy controls (p < 0.001). MVs were significantly correlated with procoagulant MVs, D-Dimer levels, fibrinogen, and IL-6, but not with platelet, lymphocyte, and neutrophil counts. Conclusion: Elevated levels of procoagulant MVs and their association with inflammatory and coagulation markers in patients with COVID-19 are suggested as a novel circulatory biomarker to evaluate and predict the procoagulant activity and severity of COVID-19. [ABSTRACT FROM AUTHOR]

AbstractIt is common practice in laboratories to store biological samples in ultra-low temperature (ULT) freezers. There is growing interest in raising the temperature of ULT freezers in order to save energy and reduce expenses, as energy conservation becomes increasingly important and sustainable laboratory practices gain popularity. In our laboratory, plasma samples are stored for three months for diagnostic purposes. We therefore took the opportunity to investigate the effect of two different storage temperatures (−70 °C vs −80 °C), on activated partial thromboplastin time (APTT), factor VIII (FVIII), international normalized ratio (INR) and factor VII (FVII) measurements on paired plasma samples collected from 26 individuals after three months of storage. Automated coagulation analysers CS-5100 and ACL TOP were used to perform the tests. We found no consistent difference between the two storage temperatures for any of the four coagulation parameters (all p-values > 0.05). We conclude that the temperature of ULT freezers used to store plasma samples for APTT, FVIII, INR, and FVII measurements can be safely increased from −80 to −70 °C without affecting the stability of the samples. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized classical treatment approaches of various cancer entities, but are also associated with a number of side effects. One of these may be life-threatening clotting disorders with the risk of thrombotic or hemorrhagic complications, the mechanisms of which are still poorly understood. In the present study, we analyzed the direct effects of pembrolizumab, nivolumab, and ipilimumab on platelet aggregation as well as plasma coagulation followed by fibrinolysis in an ex vivo model. Methods: Microplate spectrometry was used to analyze aggregation, coagulation, and fibrinolysis in platelet-free (PFP) and platelet-rich (PRP) healthy donor plasma samples treated with pembrolizumab, nivolumab, ipilimumab, and appropriate isotype controls. Aggregation was induced by TRAP-6. Clotting of PFP and PRP followed by lysis was initiated with a tissue factor in a mixture of phosphatidylserine:phosphatidylcholine and the addition of t-PA. Among other parameters, the area under the curve (AUC) was used to compare the effect of ICIs on aggregation, coagulation, and fibrinolysis. Results: Upon direct contact with platelets, pembrolizumab stimulated platelet aggregation in PRP, while nivolumab and ipilimumab promoted disaggregation with corresponding changes in the AUC. Pembrolizumab and nivolumab, both PD-1 receptor inhibitors, had no effect on the plasma coagulation cascade. Ipilimumab, a CTLA-4 receptor inhibitor, significantly increased the rate of PRP clotting. When clotting was followed by lysis, all ICIs were found to prolong the growth of the PRP-derived fibrin clot and delay its elimination. This was manifested by an increase in AUC relative to control PRP. Conclusion: This study characterizes the potential impact of pembrolizumab, nivolumab, and ipilimumab on hemostasis. Nivolumab and ipilimumab are able to reduce aggregation and increase the procoagulant properties of platelets, which can cause side effects associated with hemostatic imbalance leading to thrombosis or bleeding. The observed ICI-specific effects may contribute to our understanding of the mechanisms by which ICI affects platelets and suggest how, in a clinical setting, to reduce coagulation disorders during ICI treatment in the future. [ABSTRACT FROM AUTHOR]

As the health impact of ultrafine particles is getting better understood, modelling the size distribution and the number concentration with chemistry transport models becomes an increasingly important matter. The number concentrations is strongly affected by processes linked to aerosol dynamics: coagulation, condensation and gas/particle phase partitioning, nucleation. Coagulation is usually solved using an Eulerian approach, using a fixed diameter size discretization. In opposition, condensation/evaporation is rather solved using a Lagrangian approach, requiring redistribution of particles on the fixed grid size. Here, a new analytic formulation is presented to compute efficiently coagulation partition coefficients, allowing to dynamically adjust the discretization of the coagulation operator to the Lagrangian size mesh evolution, and therefore solve all the processes linked to aerosol dynamics with a Lagrangian approach, avoiding the redistribution on the fixed size grid. This new approach has the advantage of reducing the numerical diffusion introduced by condensation. The significance of these effects on number concentrations is assessed over Greater Paris with the chemistry transport model Polyphemus/Polair3D coupled to the aerosol model SSH-aerosol, using different size resolution of the particle distribution. [ABSTRACT FROM AUTHOR]

It is undeniable that removal efficiency is the main factor in coagulation-flocculation (C-F) process for wastewater treatment. However, as far as environmental safety is concerned, the ecotoxicological aspect of the C-F process needs to be examined further. In this study, a systematic review was performed based on publications related to the toxicity research in C-F technology for wastewater treatment. Through a series of screening steps, available toxicity studies were categorized into four themes, namely acute toxicity, phytotoxicity, cytotoxicity, and genotoxicity, which comprised 48 articles. A compilation of the methodologies executed for each theme was also outlined. The findings show that conventional metallic coagulants (e.g., alum, iron chloride, and iron sulfate) were less toxic when tested on test species such as Daphnia magna (water flea), Lattuca sativa (lettuce), and animal cells compared to synthetic polymers. Natural coagulants such as chitosan or Moringa oleifera were less toxic compared to metallic coagulants; however, inconsistent results were observed. Moreover, an advanced C-F (electrocoagulation) as well as integration between C-F and Fenton, adsorption, and photocatalytic does not significantly change the toxicological profile of the system. It was found that diverse coagulants and flocculants, species sensitivity, complexity in toxicity testing, and dynamic environmental conditions were some key challenges faced in this field. Finally, it was expected that advances in technology, interdisciplinary collaboration, and a growing awareness of environmental sustainability will drive efforts to develop more effective and eco-friendly coagulants and flocculants, improve toxicity testing methodologies, and enhance the overall efficiency and safety of water and wastewater treatment processes. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and inhospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs. [ABSTRACT FROM AUTHOR]

The hemostatic system is characterized by a delicate balance between pro- and anticoagulant forces, and the smallest alteration can cause serious events such as hemorrhages or thrombosis. Although exercise has been shown to play a protective role in athletes, several factors may increase the risk of developing venous thromboembolism (VTE), including hemoconcentration induced by exertion, immobilization following sports injuries, frequent long-distance flights, dehydration, and the use of oral contraceptives in female athletes. Biomarkers such as D-dimer, Factor VIII, thrombin generation, inflammatory cytokines, and leukocyte count are involved in the diagnosis of deep vein thrombosis (DVT), although their interpretation is complex and may indicate the presence of other conditions such as infections, inflammation, and heart disease. Therefore, the identification of biomarkers with high sensitivity and specificity is needed for the screening and early diagnosis of thromboembolism. Recent evidence about the correlation between the intensity of physical activity and VTE is divergent, whereas the repeated gestures in sports such as baseball, hockey, volleyball, swimming, wrestling, or, on the other hand, soccer players, runners, and martial art training represent a risk factor predisposing to the onset of upper and lower DVT. Anticoagulant therapy is the gold standard, reducing the risk of serious complications such as pulmonary embolism. The aim of this review is to provide a general overview about the interplay between physical exercise and the risk of thromboembolism in athletes, focusing on the main causes of thrombosis in professional athletes and underlying the need to identify new markers and therapies that can represent a valid tool for safeguarding the athlete's health. [ABSTRACT FROM AUTHOR]

Tissue factor (TF) is a transmembrane glycoprotein that represents the fundamental physiological initiator of the coagulation cascade through its interaction with factor VII. TF belongs to the cytokine receptor protein superfamily and contributes to the transduction of cellular signaling. Therefore, TF-related pathways are involved in multiple pathophysiological processes, not only in coagulation/thrombosis but in a wider mechanisms' panorama, ranging from infective to neoplastic diseases. Consistently, the measurement of TF activity could have a diagnostic and/or prognostic meaning in different clinical conditions. However, the transmembrane localization, the expression on different cellular types and circulating extracellular vesicles, and the different conformations (encrypted and decrypted) and variants (such as the soluble alternatively spliced TF) hamper TF assessment in clinical practice. The activated factor VII-antithrombin (FVIIa–AT) complex is proposed as an indirect biomarker of the TF–FVIIa interaction and, consequently, of the functionally active TF expression. In this narrative review, we evaluate the clinical studies investigating the role of plasma concentration of FVIIa–AT in health and disease. Although without conclusive data, high FVIIa–AT concentrations predict the worst clinical outcomes in different pathologic conditions, such as cardiovascular disease and cancer, thereby suggesting that overactivation of TF-related pathways may play an unfavorable role in various clinical settings. [ABSTRACT FROM AUTHOR]

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In this paper, the effect of the composition of a nonsolvent bath on the physicochemical properties of the polyvinylidene fluoride (PVDF) ultrafiltration membranes were comprehensively investigated using the nonsolvent‐induced phase separation method. Three additives (ethanol, glycerol, or NaCl) were added to the water coagulation bath respectively to obtain different membranes. It was found that the microstructure of the membranes changed from finger‐like structure to the sponge‐like structure with the increase of additives concentration, which successfully improved the retention and mechanical properties of the membranes. In addition, the membrane surface became smoother and more hydrophilic. The membrane fabricated in 30 wt% glycerol bath exhibited outstanding comprehensive properties of retention and anti‐fouling, with a water flux of 243.5 L/(m2 h), a bovine serum albumin rejection of more than 90%, and a flux recovery rate of 97%. From mechanism analysis, the addition of ethanol, glycerol, or NaCl to the coagulation bath altered the thermodynamic stability of the polymer system, and slowed down the rate of solvent and nonsolvent diffusion from a kinetic perspective. This research provides important clues for optimizing the membrane properties, such as flux, rejection, and strength. [ABSTRACT FROM AUTHOR]

Summary: Chimeric antigen receptor (CAR)‐T‐cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR‐T‐cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR‐T‐cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life‐threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR‐T‐cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR‐T‐cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR‐T‐cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR‐T‐cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates. [ABSTRACT FROM AUTHOR]

Tick Anticoagulant Peptide (TAP), a 60-amino acid protein from the soft tick Ornithodoros moubata, inhibits activated coagulation factor X (fXa) with almost absolute specificity. Despite TAP and Bovine Pancreatic Trypsin Inhibitor (BPTI) (i.e., the prototype of the Kunitz-type protease inhibitors) sharing a similar 3D fold and disulphide bond topology, they have remarkably different amino acid sequence (only ~24% sequence identity), thermal stability, folding pathways, protease specificity, and even mechanism of protease inhibition. Here, fully active and correctly folded TAP was produced in reasonably high yields (~20%) by solid-phase peptide chemical synthesis and thoroughly characterised with respect to its chemical identity, disulphide pairing, folding kinetics, conformational dynamics, and fXa inhibition. The versatility of the chemical synthesis was exploited to perform structure–activity relationship studies on TAP by incorporating non-coded amino acids at positions 1 and 3 of the inhibitor. Using Hydrogen–Deuterium Exchange Mass Spectrometry, we found that TAP has a remarkably higher conformational flexibility compared to BPTI, and propose that these different dynamics could impact the different folding pathway and inhibition mechanisms of TAP and BPTI. Hence, the TAP/BPTI pair represents a nice example of divergent evolution, while the relative facility of TAP synthesis could represent a good starting point to design novel synthetic analogues with improved pharmacological profiles. [ABSTRACT FROM AUTHOR]

Significance: Aging is a complex process associated with an increased risk of many diseases, including thrombosis. This review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. Recent Advances: Aging affects blood coagulation and fibrinolysis via multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen. Age-related prothrombotic alterations are multifactorial involving enhanced platelet activation, endothelial dysfunction, and changes in coagulation factors and inhibitors. Formation of more compact fibrin clot networks displaying impaired susceptibility to fibrinolysis represents a novel mechanism, which might contribute to atherothrombosis and venous thrombosis. Alterations to fibrin clot structure/function are at least in part modulated by post-translational modifications of fibrinogen and other proteins involved in thrombus formation, with a major impact of carbonylation. Fibrin clot properties are also involved in the efficacy and safety of therapy with oral anticoagulants, statins, and/or aspirin. Critical Issues: Since a prothrombotic state is observed in very elderly individuals free of diseases associated with thromboembolism, the actual role of activated blood coagulation in health remains elusive. It is unclear to what extent oxidative modifications of coagulation and fibrinolytic proteins, in particular fibrinogen, contribute to a prothrombotic state in healthy aging. Future Directions: Ongoing studies will show whether novel therapies that may alter oxidative stress and fibrin characteristics are beneficial to prevent atherosclerosis and thromboembolic events associated with aging. [ABSTRACT FROM AUTHOR]

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate. [ABSTRACT FROM AUTHOR]

Background and Purpose: More evidence supports the benefits of batroxobin combined with anticoagulation in correcting acute cerebral venous thrombosis (CVT). The dynamic fluctuations of peripheral blood platelets, fibrinolysis, and coagulation biomarkers during this therapy were analyzed. Methods: We investigated batroxobin's effects on the antithrombotic system under two regimens. The pretreatment group included patients on anticoagulants for at least 1 week before starting batroxobin. The simultaneous treatment group began both treatments upon admission. The control group received only anticoagulation. Batroxobin was given on alternate days at doses of 10BU, 5BU, and 5BU, totaling three doses. Anticoagulation was continuous. Baseline data were T0; the next day after each batroxobin dose was T1, T2, and T3. Data from these four time points was analyzed. Results: The time‐point paired sample T‐test results of the pretreatment group [n = 60; mean age (SD), 43.3(16.5); 38 (63.35%) women] showed that batroxobin significantly inhibited ADP‐induced platelet aggregation rate (T1–T0: p = 0.015; T2–T0: p = 0.025; T3–T0: p = 0.013), decreased fibrinogen level (T1–T0: p < 0.001; T2–T0: p < 0.001; T3–T0: p < 0.001), and increased D‐dimer (T1–T0:p < 0.001; T2–T0: p < 0.001; T3–T0: p < 0.001), TT (T1–T0:p = 0.046; T2–T0: p = 0.003; T3–T0: p < 0.001), and APTT (T1–T0:p = 0.021; T2–T0: p = 0.012; T3–T0: p = 0.026). Compared to the control group, the simultaneous treatment group showed significantly higher TT (T2: p = 0.002; T3: p = 0.004) and D‐dimer (T1: p < 0.001; T2: p < 0.001; T3: p < 0.001) values, while fibrinogen (T2: p < 0.001; T3: p < 0.001) levels were significantly lower. Using batroxobin can alleviate the amplitude of changes in coagulation indicators other than TT caused by anticoagulants. The above conclusions are consistent with the results of repeated measurement data analysis. Conclusions: Batroxobin can significantly inhibit ADP‐induced platelet aggregation rate, increase D‐dimer, decrease fibrinogen, and prolong TT and APTT in the presence of anticoagulant agents. Using batroxobin can reduce the amplitude of changes in coagulation indicators caused by anticoagulants. These results reveal the potential mechanism of batroxobin combined with anticoagulation in the safe and effective treatment of CVT. [ABSTRACT FROM AUTHOR]

Background: Understanding the recovery of post‐COVID‐19 organ dysfunction is essential. We evaluated coagulation 6 months post‐COVID‐19, examining its recovery and association with lung function. Methods: Patients treated for COVID‐19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D‐dimer) during the 6 months post‐hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin‐corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post‐hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates. Results: Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID‐19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D‐dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D‐dimer in 27% (18/67) at 6 months. A weak negative correlation (r = −0.37, p =.036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%. Conclusion: Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID‐19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity. [ABSTRACT FROM AUTHOR]

Reticulated platelets (RePLT) are emergency circulating platelets released to contrast peripheral platelet destruction. We conducted a prospective study to [a] characterize RePLT in cirrhosis; [b] evaluate the association between RePLT and hepatic decompensation/death. Cirrhosis patients without hepatocellular carcinoma were prospectively recruited and underwent assessment of RePLT and thrombopoietin (TPO). RePLT were evaluated by cytofluorimetry and immuno-fluorescence microscopy. Twenty healthy subjects were included as controls. Patients were followed for 6 months for hepatic decompensation and further decompensation/ACLF. Forty-five patients were included (Child-Pugh [CP] A/B/C 18/11/16). Compared to controls, RePLT in cirrhosis were significantly increased (0.82% vs. 0.05%; p < 0.001) and hyperactivated (4.35% vs. 0.17%; p = 0.004). No correlation was observed between RePLT and CP, platelet count, TPO, MELD score, and C-reactive protein. TPO was lower in cirrhosis than controls (28 pg/mL vs. 52 pg/mL; p = 0.005), decreasing significantly with CP stage. In CP B/C patients (n = 27), RePLT were significantly higher in those who progressed towards further decompensation/ACLF (2.11 [0.56–2.95] vs. 0.69 [0.02–1.22]; p < 0.01). A proportion of RePLT >2% accurately identified high-risk patients (AUROC 0.818; 95%CI: 0.639–0.997; sensitivity 94%, specificity 73%). RePLT in cirrhosis are increased and hyper-activated. In decompensated patients, higher RePLT appear to be associated with worse outcomes. [ABSTRACT FROM AUTHOR]

The PNIPAM/PAphe interpenetrating nanogels which were responsive to temperature and pH were synthesized. The chemical structure, morphology, particle size and dispersity, temperature-and pH-response, structural color tunability, photonic crystal self-assembly, and sol-gel transition behavior of the interpenetrating nanogels were studied in detail by infrared spectroscopy, scanning electron microscopy (SEM), dynamic light scattering, and optical fiber spectrometry. According to the infrared spectrum and SEM image, the effective interpenetration and good monodispersity of the two networks were confirmed. The analysis of particle size and polydispersity index (PDI) indicated that, with the increase of PAphe content, the particle size of the interpenetrating nanogels correspondingly increased, but the monodispersity remained good. The temperature-and pH-sensitivity experiments proved the responsiveness of the interpenetrating nanogels, which showed that the particle size was significantly decreased when the temperature was increased or the pH value was decreased. Combined with the optical fiber spectrum, it was further found that the interpenetrating nanogel could achieve controllable structural colors by adjusting the particle size. More importantly, they possessed the ability of transition from sol to gel above Tp (32 °C) by the method of test tube inversion. These characteristics showed their potential applications in highly controllable optical materials and the biomedical field. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony‐stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. Methods: We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. Results: The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. Conclusion: We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM. [ABSTRACT FROM AUTHOR]

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections. [ABSTRACT FROM AUTHOR]

Purpose: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT). Materials and Methods: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention. Results: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950–3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999–3.909, p=0.05). Conclusions: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes. Clinical Impact: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease. [ABSTRACT FROM AUTHOR]

Reverse osmosis (RO) membranes have been widely applied in the advanced treatment of chemical mechanical polishing (CMP) wastewater. However, membrane fouling persists in practical treatment processes. Herein, a hybrid coagulation-ultrafiltration (UF)-RO (CUR) system was used to control the fouling of the RO membrane, and a novel composite coagulant was developed to enhance the coagulation efficacy for CMP wastewater. Compared to traditional processes, the improved Coagulation-UF process exhibited a remarkable capacity, removing 98.62% of total silica and achieving complete turbidity removal in CMP wastewater. Furthermore, the aluminum residual was reduced by 76.47%, and the normalized flux of the RO membrane increased from 0.87 to 0.95. Moreover, the new coagulant achieved remarkable coagulation effectiveness, with silica and turbidity removal rates reaching 97.29% and 99.87%, respectively, while reducing residual aluminum to 15.50%. Notably, dissolved silica in CMP wastewater emerged as the primary contaminant on the surface of the RO membrane. The net sweep was the primary coagulation mechanism of the new coagulant, proving good performance in reducing the burden on both UF and RO membranes. These results exhibit significant implications for designing efficient pretreatment schemes for CMP wastewater and optimizing the longevity of RO membranes in semiconductor plants. [ABSTRACT FROM AUTHOR]

Clarias species used in aquaculture are suffering from inbreeding depression with its attendant poor reproductive attributes and there is the need to explore the natural population to improve reproductive performance. Therefore, this work aimed at evaluating the morpho-genetic variability among wild and cultured Clarias garipinus available in Ogbomoso, South-Western, Nigeria. Fifty C. gariepinus samples were obtained from the wild and cultured populations and only ten were favoured for this work. The DNA was extracted from the caudal peduncles of five representatives of the two sampled populations and DNA amplification was done using cytochrome oxidase region's COX1. Predictive Analytics Software version 20.0 was used for data analyses. Results showed that virtually all morphometric parameters measured were significantly higher in the cultured populations compared to the wild except the dorsal fin length (p=0.346). The A260/280 ratio ranges from 1.85 (C1) to 2.11 (W2), with most samples having a ratio close to 2.0, indicating high-purity DNA, which is around standard recommended DNA concentration for the amplification. The DNA amplified at 700 bp from a portion of mitochondrial DNA (mtDNA) of wild and cultured Clarias gariepinus. The genetic distance between each strain is represented by the length of the branch that connects them. Therefore, these suggest that C. gariepinus breeders and farmers should source C. gariepinus species from the wild in order to genetically enrich the gene pool. Additionally, head region-based morphometric traits might be more informative in distinguishing wild and cultured populations of C. gariepinus. [ABSTRACT FROM AUTHOR]

Catalytic converters have now been largely employed to significantly reduce the levels of carbonbased particles into the atmosphere, however, this approach generates nanoparticles (NPs) that are often released as fine airborne particles into the atmosphere, having abilities to remain suspended in the atmosphere for long durations and find their way into the human lung cells, and eventually into the blood stream. This could result in triggering the body's innate immune system. In this study, we exposed blood samples from healthy individuals to Platinum nanoparticles and compared the results to the effects induced by the thrombogenic TiO2, to investigate the response mechanisms of the blood cells and innate immune system to these particles. Results showed a clear activation of coagulation system in samples treated with both NPs, compared with untreated blood samples. TiO2 NPs had significantly higher coagulation effect (84% platelet consumption) compared to the platinum NPs (38% platelet consumption), while blood samples without NPs showed only a 14% platelet consumption. Also, TiO2 NPs and Pt NPs induced slightly similar complement activation in blood samples as measured from the generated C3a (921±16.70 µg/L and 826±27.50 µg/L respectively) and sC5b-9 (136±3.46 µg/L and 138±6.49 µg/L respectively) components. However, blood samples without NPs exhibited significantly lower C3a and sC5b-9 components (522±22.50 µg/L and 101±4.70 µg/L respectively). The latter demonstrated the potential risks exposed to by urban dwellers, such as cascading inflammatory and thrombotic responses, there is need for more investigation on the patho-serological events that can be triggered by other airborne fine particles. [ABSTRACT FROM AUTHOR]

Background: According to the International Standard (ISO10993-4), a test model using human blood must be used for blood compatibility evaluation of medical devices. However, various safety investigations have reported outcomes from animal models simulating clinical conditions. Additionally, the validation of animal blood in blood compatibility assessment models is limited. In this study, the differences in the reactivity of different species to coagulation and complement, as well as the main mechanisms governing blood clot formation upon contact with medical devices, were examined. Moreover, it aimed to acquire information required to design a hemocompatibility evaluation model and interpret the results. Results: Rabbits, porcine, rhesus monkeys, and cynomolgus monkeys were exposed to one negative and two positive control substances, and variations in the partial thromboplastin time (PTT) were observed. The activity of the complement system was observed in accordance with the test method in ISO 10993-4. Although the PTT absolute values varied across animal species, the normalized PTT values—61% for rabbits, 66% for pigs, 63% for rhesus monkeys, and 65% for cynomolgus monkeys—exhibited no statistically significant differences. After reacting human and porcine sera with the material, the test model using human serum distinguished the positive and negative control candidates, whereas the test model using porcine serum could not discriminate them. Conclusions: These results suggest similar reactivity in blood coagulation across species after substance contact. However, complement system activity indicated a significant difference in reactivity between human and porcine blood. This finding will be useful in the design of a blood compatibility evaluation model for medical devices and interpretation of the results. [ABSTRACT FROM AUTHOR]

The electrical conductivity of traditional medical fibers was enhanced through in-situ polymerization of dopamine, resulting in the fabrication of a PET@PDA flocking fabric using electrostatic flocking technology. The response surface methodology was employed to optimize the parameters of the flocking process, and regression models were established to analyze the relationship between flocking process parameters and flocking density, specific surface area. An evaluation was conducted on the appearance, mechanical properties, cell compatibility, and blood compatibility of PET@PDA flocked fabric. The results demonstrate that PET@PDA10-2 flocking fabric exhibits high vertical orientation, significant porosity, excellent compression recovery performance (98.10% recovery rate under 50% strain), as well as favorable cytocompatibility and blood compatibility with remarkable coagulant promoting ability. Therefore, the electrostatically flocked PET@PDA fabric holds promising potential for applications in anticoagulant materials. [ABSTRACT FROM AUTHOR]

Background: Coagulation abnormalities are common in sepsis patients and are associated with increased mortality. This study aimed to assess the hemostatic profile of sepsis patients using rotational thromboelastometry (ROTEM) and to find the ROTEM parameters best predicting short-term mortality. Methods: We conducted a prospective analysis of consecutive sepsis patients hospitalized in the intensive care unit. The inclusion criteria were diagnosis of sepsis or septic shock and pro-calcitonin concentration >0.5 ng mL−1. Clinical, standard laboratory, and ROTEM analyses were performed. Results: The study group comprised 38 (49%) males and 40 (51%) females. Median Sequential Organ Failure Assessment (SOFA) score was 8 (interquartile range IQR 5–11) points. The most common primary sites of infection were pneumonia (n = 27/35%), intra-abdominal (n = 27/35%), urinary tract infection (n=20/26%), and others (n = 4/6%). The following parameters evaluating fibrinogen function were outside the reference range: clotting time (CT), clot amplitude (A) at 10 and 20 min, and maximal clot firmness (MCF). Out of 78 patients, 28 (36%) died in the intensive care unit. Significant differences between survivors and non-survivors of sepsis were present for the ROTEM parameters assessing fibrinolytic activity. Conclusions: ROTEM in the early phase of sepsis reveals increased coagulation mediated through the function of fibrinogen. Non-survivors showed slightly lower fibrinolytic activity than survivors; however, it was still within test reference values. The highest predicting value was obtained by a model incorporating, among others, extrinsic coagulation pathway fibrinolytic parameters. [ABSTRACT FROM AUTHOR]