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Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

Aim: In this study, we evaluated the effects of two types of hydroxyapatite (HAP) nanoparticles, sharing the same surface chemistry but differing in shape, on the biological characteristics of plasma, platelets and red blood cells. Materials & methods: Initially, two different shapes (rod-shaped and sphere-shaped) of HAPs were characterized. These HAPs were then co-cultured with plasma and red blood cells to examine their impact on coagulation and hemolysis. The impact of HAPs on white blood cells count in mice were evaluated following gavage and tail vein injection. Results: Sphere-shaped HAP is more likely to adsorb onto platelet surfaces, while rod-shaped HAP is more likely to cause hemolysis. Although there are differences in the in vitro experimental results between sphere-shaped HAP and rod-shaped HAP, both types demonstrate good blood compatibility at a 20 mM concentration. Furthermore, in vivo experiments showed that sphere-shaped nano-HAP induced a more pronounced increase in white blood cell count, suggesting that it may exhibit greater toxicity. Conclusion: While differences exist in the blood compatibility test results between the two HAPs, these differences are minimal, with both results falling within a safe range. Overall, HAP demonstrates excellent blood compatibility. Article highlights Despite the increasingly widespread application of nanoparticles in the biomedical field, the impact of nanoparticle shape on the biological characteristics of blood cells and plasma components remains inadequately characterized. To address this knowledge gap, we conducted a systematic evaluation of the biological effects of two hydroxyapatite (HAP) nanoparticle suspensions with different shapes (rod-shaped and sphere-shaped) but identical surface chemical properties on various blood components, including coagulation factors, platelets and red blood cells. Our findings demonstrated that these two HAP nanoparticles did not cause adverse reactions, such as plasma coagulation, platelet activation or red blood cell hemolysis at a concentration of 20 mM, indicating their good blood compatibility at this concentration. In vivo experiments at a dose of 500 μM/kg showed that both gastric lavage and tail vein injection of HAP induced an increase in white blood cell count in the experimental animals, indicating potential early and late inflammatory responses. [ABSTRACT FROM AUTHOR]

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A kind of nitrile rubber (NBR) with high bound acrylonitrile content was prepared by low-temperature emulsion-polymerization and the sequence structure of the polymer was characterized by proton nuclear magnetic resonance spectroscopy, and the effects of different coagulants on the coagulation behavior and physico-mechanical properties of the polymer were studied. The results showed that the BAA sequence structure appeared in NBR with high bound acrylonitrile content, and the content of BAA, BAB, and ABA sequence structures increased gradually and that of BBB and BBA sequence structures decreased gradually with the increase in bound acrylonitrile content; the coagulation efficiency of CaCl2 and Al2(SO4)3 was much higher than those of NaCl and H2SO4, and the coagulation efficiency of the first two both reached about 98%; Al2(SO4)3 could improve the hardness, tensile strength, modulus, and elongation at break of NBR, and the elongation at break of NBR prepared from Al2(SO4)3 was 566%.

Introduction: The Covid-19 disease causes many clinical and paraclinical symptoms, each of these symptoms may be effective in diagnosing the disease or determining the trend of the disease. Coagulation system changes in Covid-19 inpatients were evaluated in this study. Methods and Materials: In a descriptive/cross-sectional study, 90 Covid-19 hospitalized patients in Hamedan were selected. Moreover, their coagulation system changes including platelet count (Plt), PT, PTT, FDP, MPV and D-Dimer were investigated on the first and seventh days of admission. Data analysis was performed with SPSS software version 26. Wilcoxon test was used quantitatively and Mc Nemar test was used qualitatively in order to compare the coagulation system changes on the first and seventh days of hospitalization. Results: The mean age of the patients was 51.61 years. 53.33% of these patients were male and 46.64% of them were female. On the first and seventh days of hospitalization, the mean and standard deviation of coagulation system changes were as follow respectively; PT: 12.71±1.69 and 15.00±2.39 seconds (P<0.001), PTT: 33.5±8.09 and 43.11±32.31 seconds (P<0.001), Plt: 276.58±18.30 and 244.09±7.20 × 103/μl (P<0.001), MPV: 8.00±2.84 and 10.58±3.83 femtoliters (P<0.001), D-Dimre: 300.17±34.40 and 493.17±194.26 nanogram per milliliter (P<0.001). FDP≥5 in the seventh day was also higher than the first day of hospitalization (70% Vs 6.7%) respectively (P<0.001). Discussion and Conclusion: Coagulation system of inpatients with Covid-19 undergoes significant changes from the time of admission to the seventh day. These changes include increased levels of PT, PTT, MPV, FDP and D-Dimer biomarkers and decreased platelet count. [ABSTRACT FROM AUTHOR]

Abruptio placenta can lead to rapid separation of the placenta and result in fetal demise. Secondary to abruption, Disseminated Intravascular Coagulation (DIC) can occur due to inappropriate activation of the coagulation and fibrinolytic system. Once DIC develops, early recognition, specific treatment and repeated tests with aggressive correction of coagulation and electrolyte imbalance along with avoidance of hypothermia and metabolic acidosis help in preventing multi organ failure and mortality.

Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting that these systems could serve as promising therapeutic targets for DKD. This review aims to shed light on the underlying connections between coagulation and complement systems and their involvement in the advancement of DKD.

The coagulation and immune systems, two vital systems in the human body, share intimate connections that fundamentally determine patient health. These systems work together through several common regulatory pathways, including the Tissue Factor (TF) Pathway. Immune cells expressing TF and producing pro-inflammatory cytokines can influence coagulation, while coagulation factors and processes reciprocally impact immune responses by activating immune cells and controlling their functions. These shared pathways contribute to maintaining health and are also involved in various pathological conditions. Dysregulated coagulation, triggered by infection, inflammation, or tissue damage, can result in conditions such as disseminated intravascular coagulation (DIC). Concurrently, immune dysregulation may lead to coagulation disorders and thrombotic complications. This review elucidates these intricate interactions, emphasizing their roles in the pathogenesis of autoimmune diseases and cancer. Understanding the complex interplay between these systems is critical for disease management and the development of effective treatments. By exploring these common regulatory mechanisms, we can uncover innovative therapeutic strategies targeting these intricate disorders. Thus, this paper presents a comprehensive overview of the mutual interaction between the coagulation and immune systems, highlighting its significance in health maintenance and disease pathology. [ABSTRACT FROM AUTHOR]

Introduction: Narcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes. Methods: To gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer. Results and discussion: Our study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system. [ABSTRACT FROM AUTHOR]

Justyna Hajtuch,1 Eliza Iwicka,1 Anna Szczoczarz,1 Damian Flis,1 El&zdot;bieta Megiel,2 Piotr Cieciórski,2 Marek Witold Radomski,3 Maria Jose Santos-Martinez,4 Iwona Inkielewicz-Stepniak1 1Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Gdansk, Poland; 2Faculty of Chemistry, University of Warsaw, Warsaw, Poland; 3Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 4School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Trinity College Dublin, Dublin, Dublin 2, IrelandCorrespondence: Iwona Inkielewicz-Stepniak, Tel +48 58 349 1516, Fax +48 58 349 1517, Email iwona.inkielewicz-stepniak@gumed.edu.plPurpose: In the search for new drug delivery platforms for cardiovascular diseases and coating of medical devices, we synthesized eptifibatide-functionalized silver nanoparticles (AgNPs-EPI) and examined the pharmacological activity of AgNPs-EPI on platelets and endothelial cells in vitro and ex vivo.Methods: Spherical AgNPs linked to eptifibatide were synthesized and characterized. Cytotoxicity was measured in microvascular endothelial cells (HMEC-1), platelets and red blood cells. Platelet mitochondrial respiration was measured using the Oxygraph-2k, a high-resolution modular respirometry system. The effect of AgNPs-EPI on the aggregation of washed platelets was measured by light aggregometry and the ex vivo occlusion time was determined using a reference laboratory method. The surface amount of platelet receptors such as P-selectin and GPIIb/IIIa was measured. The influence of AgNPS-EPI on blood coagulation science was assessed. Finally, the effect of AgNPs-EPI on endothelial cells was measured by the levels of 6-keto-PGF1alpha, tPa, cGMP and vWF.Results: We describe the synthesis of AgNPs using eptifibatide as the stabilizing ligand. The molecules of this drug are directly bonded to the surface of the nanoparticles. The synthesized AgNPs-EPI did not affect the viability of platelets, endothelial cells and erythrocytes. Preincubation of platelets with AgNPs-EPI protected by mitochondrial oxidative phosphorylation capacity. AgNPs-EPI inhibited aggregation-induced P-selectin expression and GPIIb/IIIa conformational changes in platelets. AgNPs-EPI caused prolongation of the occlusion time in the presence of collagen/ADP and collagen/adrenaline. AgNPs-EPI regulated levels of 6-keto-PGF1alpha, tPa, vWf and cGMP produced in thrombin stimulated HMEC-1 cells.Conclusion: AgNPs-EPI show anti-aggregatory activity at concentrations lower than those required by the free drug acting via regulation of platelet aggregation, blood coagulation, and endothelial cell activity. Our results provide proof-of-principle evidence that AgNPs may be used as an effective delivery platform for antiplatelet drugs.Graphical Abstract: Keywords: drug delivery, antiplatelet, RGD, aggregation, coagulation system, biocompatibility

Background and Aim Coronavirus disease 2019 (COVID-19) is a respiratory disorder that can affect many body systems, including the hemostatic system. In this study, we aim to investigate the role of hemostatic system and the blood coagulation in COVID-19. Methods & Materials In this review study, the articles were searched using the keywords COVID-19, Respiratory infection, and Coagulopathy in Google Scholar, PubMed, Google Springer and Science Direct databases. Ethical Considerations Ethical principles in writing this article were observed in accordance with the guidelines of the National Ethics Committee and the Committee on Publication Ethics (COPE). Results Many changes in the coagulation profile of infected patients were reported, including changes in the platelet count, fibrinogen/fibrin degradation product, D-Dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time. With the increase in the number of patients with COVID-19, several studies found out the occurrence of thrombosis and coagulopathy in patients. Conclusion Due to the increase in the occurrence of coagulation disorders in patients with COVID-19, the administration of anticoagulants is needed for their treatment; it can play an effective role in improving the prognosis of patients.

IntroductionNarcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes.MethodsTo gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer.Results and discussionOur study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system.

Abstract Background Increasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC). Methods A retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis. Results We involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047; p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491; p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768; p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894; p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241; p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS and p = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS and p = 0.0180 for OS). Conclusion Our findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.

Background and Aim: COVID-19 disease is considered a respiratory disorder that can affect many body systems, including the hemostasis system, so in this review article, according to the latest findings, we investigate the role of the blood coagulation system in COVID-19 infection. Materials and Methods: In this review study, the articles were searched in Medline database using keywords such as “Respiratory infection”, “COVID-19”, “Coagulopathy” . Ethical Considerations: Ethical principles in writing this article have been observed in accordance with the guidelines of the National Ethics Committee and the Committee on Publication Ethics (COPE). Results: In December 2019, a sudden outbreak of acute respiratory syndrome caused by a new type of coronavirus was reported for the first time in Wuhan, Hubei Province, China. The World Health Organization (WHO) named this virus COVID-19 and the International Committee on Classification of Viruses (ICTV) named it SARS-CoV-2. Many changes in the coagulation profile of COVID-19 patients have been reported, which include changes in the number of platelets as well as changes in coagulation indices such as FDP, D-Dimer, fibrinogen, PT and PTT. With the increase in the number of patients with COVID-19 infection, researchers found out the occurrence of thrombosis and coagulopathy in patients with COVID-19 through numerous investigations. Conclusion: Due to the increase in the occurrence of coagulation disorders in COVID-19 patients, the administration of anticoagulants is necessary as one of the important arms of the treatment of patients with COVID- 19 and can play an effective role in improving the prognosis of patients. [ABSTRACT FROM AUTHOR]

Here, we discuss blood management upon a risk of massive obstetric hemorrhage by describing a clinical case of female patient with obstetric complications of pregnancy such as severe preeclampsia and chronic placental insufficiency with fetal malnutrition examined by using thromboelastometry to assess a risk of developing massive obstetric hemorrhage. A rotational thromboelas-tography/thromboelastometry technology as well as available publications related to using it in obstetrics are outlined.

The coagulation cascade and fibrinolysis have links with neuroinflammation and increased activation of the coagulation system has been reported in MS patients. We quantified levels of D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and the bioactivity of bacterial lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) and plasma from newly diagnosed untreated MS patients and controls. These molecules showed multiple correlations with each other as well as with age, HLA-DRB1*15:01, body-mass-index and CSF IgG. Our results confirm previous findings of increased plasma PAI-1 and LPS in MS patients compared to controls indicating changes in platelet function and gut permeability in MS., Competing Interests: Declaration of competing interest JL: Congress expenses, Merck. PJT: Lecture and consulting fees Roche, Merck, Biogen, Novartis, Janssen, Sanofi, Alexion; congress expenses Biogen, Merck. KKE: Lecture fees: Novartis, Celltrion, Sobi., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

ObjectiveSome patients with pancreatic ductal adenocarcinoma (PDAC) are prone to rapid recurrence or metastasis after radical resection. However, evaluation methods for effectively identifying these patients are lacking. In this study, we established perioperative serum scoring systems to screen patients with early recurrence and poor prognosis.MethodsWe systematically analysed 44 perioperative serum parameters, including systemic inflammatory parameters, coagulation system parameters, tumor markers, and 18 clinicopathological characteristics of 218 patients with radical resection in our centre. Univariate Cox regression and LASSO regression models were used to screen variables. Kaplan-Meier survival analysis was used to compare relapse-free survival and overall survival. Multivariate Cox regression was used to evaluate the independent risk variables. AUC and C-index were used to reveal the effectiveness of the models. In addition, the effectiveness was also verified in an independent cohort of 109 patients.ResultsPreoperative systemic immune coagulation cascade (SICC) (including increased neutrophil to lymphocyte ratio, decreased lymphocyte to monocyte ratio, increased platelet and fibrinogen) and increased postoperative tumor markers (TMs) (CA199, CEA and CA242) were independent risk factors for early recurrence of resectable pancreatic cancer. On this basis, we established the preoperative SICC score and postoperative TMs score models. The patients with higher preoperative SICC or postoperative TMs score were more likely to have early relapse and worse prognosis. The nomogram based on preoperative SICC, postoperative TMs, CACI, smoking index, vascular cancer embolus and adjuvant chemotherapy can effectively evaluate the recurrence rate (AUC1 year: 0.763, AUC2 year: 0.679, AUC3 year: 0.657) and overall survival rate (AUC1 year: 0.770, AUC3 year: 0.804, AUC5 year: 0.763).ConclusionPreoperative SICC and postoperative TMs can help identify resectable PDAC patients with early recurrence and poor prognosis.

Objective: Some patients with pancreatic ductal adenocarcinoma (PDAC) are prone to rapid recurrence or metastasis after radical resection. However, evaluation methods for effectively identifying these patients are lacking. In this study, we established perioperative serum scoring systems to screen patients with early recurrence and poor prognosis. Methods: We systematically analysed 44 perioperative serum parameters, including systemic inflammatory parameters, coagulation system parameters, tumor markers, and 18 clinicopathological characteristics of 218 patients with radical resection in our centre. Univariate Cox regression and LASSO regression models were used to screen variables. Kaplan-Meier survival analysis was used to compare relapse-free survival and overall survival. Multivariate Cox regression was used to evaluate the independent risk variables. AUC and C-index were used to reveal the effectiveness of the models. In addition, the effectiveness was also verified in an independent cohort of 109 patients. Results: Preoperative systemic immune coagulation cascade (SICC) (including increased neutrophil to lymphocyte ratio, decreased lymphocyte to monocyte ratio, increased platelet and fibrinogen) and increased postoperative tumor markers (TMs) (CA199, CEA and CA242) were independent risk factors for early recurrence of resectable pancreatic cancer. On this basis, we established the preoperative SICC score and postoperative TMs score models. The patients with higher preoperative SICC or postoperative TMs score were more likely to have early relapse and worse prognosis. The nomogram based on preoperative SICC, postoperative TMs, CACI, smoking index, vascular cancer embolus and adjuvant chemotherapy can effectively evaluate the recurrence rate (AUC1 year: 0.763, AUC2 year: 0.679, AUC3 year: 0.657) and overall survival rate (AUC1 year: 0.770, AUC3 year: 0.804, AUC5 year: 0.763). Conclusion: Preoperative SICC and postoperative TMs can help identify resectable PDAC patients with early recurrence and poor prognosis. [ABSTRACT FROM AUTHOR]

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model.

In liver diseases, most commonly in the terminal stage of liver failure, a variety of hemostatic defects affecting almost all parts of the blood coagulation system are developing. This leads to diminishing the capabilities of patients with liver diseases to correctly maintain the hemostatic balance.The severity of hemostatic disorders depends on the nosological form and degree of a liver damage. Depending on the imbalance of the hemostasis system and accumulated clinical/laboratory data, patients with liver diseases can be subdivided into three groups as exhibiting: 1. non-cholestatic liver damage; 2. cholestatic liver damage and 3. liver damage of vascular origin.The first part of the review discusses multiple alterations in the hemostasis system in patients with noncholestatic liver diseases, which are commonly accompanied by hypocoagulation.

Background: Increasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC). Methods: A retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis. Results: We involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047; p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491; p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768; p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894; p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241; p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS and p = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS and p = 0.0180 for OS). Conclusion: Our findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages. [ABSTRACT FROM AUTHOR]

Coagulopathy and derangements in the coagulation parameters are significant features of COVID-19 infection, which increases the risk of disseminated intravascular coagulation, thrombosis, and hemorrhage in these patients, resulting in increased morbidity and mortality. In times of COVID-19, special consideration should be given to patients with concurrent chronic kidney disease (CKD) and COVID-19 (CKD/COVID-19 patients) as renal dysfunction increases their risk of thrombosis and hemorrhage, and falsely affects some of the coagulation factors, which are currently utilized to assess thrombosis risk in patients with COVID-19. Hence, we believe extra attention should be given to determining the risk of thrombosis and bleeding and optimizing the timing and dosage of anticoagulant therapy in this unique population of patients. CKD/COVID-19 patients are considered a high-risk population for thrombotic events and hemorrhage. Furthermore, effects of renal function on paraclinical and clinical data should be considered during the evaluation and interpretation of thrombosis risk stratification. Individualized evaluation of clinical status and kidney function is necessary to determine the best approach and management for anticoagulant therapy, whereas there is a lack of studies about the population of CKD/COVID-19 patients who need anticoagulant therapy now. [ABSTRACT FROM AUTHOR]

Introduction: Spinal subdural hematoma is a rare condition among patients with neurosurgical traumas and so it is a real challenge to establish the correct preoperative diagnosis. Elevated levels of coagulation parameters are their most significant risk factors and occasionally constitute a contraindication for emergent surgery. Our study addresses the subject of the aftermath of postponing the cauda equina decompression. In this report, we describe a case of a 72-year-old obese man who presented with sharp iliolumbar pain and progressive paraparesis. Clinical examination revealed bilaterally decreased deep tendon reflexes, positive straight leg raise sign on both sides, dysaesthesia, and urinary incontinence. Imaging studies showed a mass filling almost the entire spinal canal at the L3/4 level. The surgery had to be postponed due to the excessively high international normalized ratio. The coagulation system was stabilized on the 5th day of hospitalization, hence the L2-L3-L4 laminectomy was performed. A subdural hematoma was visualized after exposing the meningeal sac. After thorough removal of the lesion and subsequent neurorehabilitation, the patient's neurological functions improved; however, urinary incontinence symptoms remained. Conclusions: Our unique case report shows potential problems with decision-making regarding the timing of the surgery. Although early decompression is characterized by the best outcome, surgeons are obliged to take into account several factors such as dysregulated coagulation system and if necessary, delay the surgery for the benefit of the patient. [ABSTRACT FROM AUTHOR]

An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the pathogenesis of COVID-19 ARDS. Biomarkers for IIIS activation were studied in the first 66 patients with COVID-19 admitted to the ICU in Uppsala University Hospital, both cross-sectionally on day 1 and in 19 patients longitudinally for up to a month, in a prospective study. IIIS analyses were compared with biochemical parameters and clinical outcome and survival. Blood cascade systems activation leading to an overreactive conjunct thromboinflammation was demonstrated, reflected in consumption of individual cascade system components, e.g., FXII, prekallikrein, and high molecular weight kininogen and in increased levels of activation products, e.g., C4d, C3a, C3d,g, sC5b-9, TAT, and D-dimer. Strong associations were found between the blood cascade systems and organ damage, illness severity scores, and survival. We show that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death. We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation. Already licensed kallikrein/kinin inhibitors are potential drugs for treatment of critically ill patients with COVID-19.

An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the pathogenesis of COVID-19 ARDS. Biomarkers for IIIS activation were studied in the first 66 patients with COVID-19 admitted to the ICU in Uppsala University Hospital, both cross-sectionally on day 1 and in 19 patients longitudinally for up to a month, in a prospective study. IIIS analyses were compared with biochemical parameters and clinical outcome and survival. Blood cascade systems activation leading to an overreactive conjunct thromboinflammation was demonstrated, reflected in consumption of individual cascade system components, e.g., FXII, prekallikrein, and high molecular weight kininogen and in increased levels of activation products, e.g., C4d, C3a, C3d,g, sC5b-9, TAT, and D-dimer. Strong associations were found between the blood cascade systems and organ damage, illness severity scores, and survival. We show that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death. We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation. Already licensed kallikrein/kinin inhibitors are potential drugs for treatment of critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy (LSG) is nowadays the most popular bariatric procedure for obesity. However, whether LSG increases the risk of thrombosis remains unclear. The aim of this study was to investigate potential effects of LSG on coagulation system. Methods: Fifty-five obese patients underwent LSG between 2016 and 2018. The LSG was performed with pneumoperitoneum pressure maintained at 13 mmHg. Venous blood specimens were collected from each patient before surgery, at the end of pneumoperitoneum (i.e., 0 h after surgery), and at 24 h after surgery to determine prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), platelet count (PLT), D-dimer (D-D), red blood cell count (RBC), hematocrit (HCT), plateletcrit (PCT), cholesterol (CHOL), triglyceride (TRIG), and serum calcium (Ca). All patients were examined on the veins of the lower limbs by color Duplex sonography (CDS) before surgery and at 24 h after surgery, respectively. Results: All patients successfully underwent LSG. No severe surgery-related complications were observed during 1-month follow-up after operation. Preoperative BMI was 43.6 ± 8.3 kg/m2. The levels of coagulation factors were within the normal range before surgery, except a relatively higher PLT. The PT and D-D were increased at 0 h and 24 h after surgery (P < 0.05), whereas APTT was decreased (P < 0.05). The postoperative FIB remained similar to the preoperative one (P > 0.05). The CDS identified no thrombus in the veins of the lower limbs, either before surgery or at 24 h after surgery. Conclusions: LSG may cause postoperative hypercoagulability of patients with obesity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of epidural anesthesia on the coagulation function of patients with pregnancy thrombocytopenia. Methods: 86 patients with pregnancy-induced thrombocytopenia admitted to our hospital from June 2018 to June 2019 were enrolled in the study. According to the random number table method, divided into study group and control group, with 43 cases in each group. The study group was given epidural anesthesia, and the control group was given general anesthesia, the changes of various indicators of maternal coagulation system before and after anesthesia were observed and compared. Results: The APTT of the study group before the anesthesia, at 0.5 h after anesthesia, at 0.5 h, 24 h, and 48 h after surgery were longer than those of the control group (PO.OS). The average blood loss and the average blood loss after 24 hours were significantly lower in the study group that in the control group (P<0.05). There was no significant difference in the Apgar scores between the two groups at 1 min and 5 min (P>0.0 5) . Conclusions: Epidural anesthesia has little effect on the coagulation function of pregnant women with thrombocytopenia, but the anesthesia has a fast onset and effective effect, and can reduce the amount of surgery and postoperative bleeding to some extent. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancies. PTC has good prognosis, but it can dedifferentiate into aggressive forms. In this study, we aimed to identify differentially expressed genes (DEGs) between PTC samples and normal controls. We used gene expression microarrays to identify DEGs between 20 PTC samples and 10 normal controls. We performed enrichment analysis to discover biological processes and signalling pathways associated with PTC and construct protein-protein interaction (PPI) networks to find out key genes for the disease. We identified 1554 up-regulated and 912 down-regulated DEGs in PTC samples compared to normal controls. The coagulation system was the most significant pathway and SERPINA1 was the most up-regulated gene of this pathway. CCND1, PGR, CEBPA, CDKN1A, SPDEF, PLAU and MDM2 were key nodes in PPI networks. Causal network analysis revealed that SFN, which was one of the up-regulated DEGs found in our study, was the most causative upstream regulator for PTC. In conclusion, deregulation of SERPINA1, CCND1, PGR, CEBPA, CDKN1A, SPDEF, PLAU and MDM2 genes and coagulation system pathway may contribute to PTC development. SFN may be an important gene in diagnosis, prognosis and novel anticancer drug approaches for PTC. Further experiments are required to confirm the functions of identified DEGs in our study. [ABSTRACT FROM AUTHOR]

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model. [ABSTRACT FROM AUTHOR]

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population. Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates. [ABSTRACT FROM AUTHOR]

Atherosclerosis concept defines the key role of inflammation in the occurrence and progression of atherosclerosis. Hemostatic system is an integral part of the inflammatory response. At all stages of atherogenesis, starting from the early stages, there is part of hemostasis factors. In recent years researchers attract most interest to the questions of intercellular interaction between platelets and leukocytes. Combined evaluation of leukocyte-platelet responses reflect the clinical and laboratory picture of atherothrombotic events in unstable angina and myocardial infarction. Monocyte-platelet interaction plays a significant role in the development of heart failure, blood platelets are capable of inducing apoptosis. The individual testing the risk of hemorrhagic complications increase the efficiency of drug prevention and therapy of antithrombotic drugs. Changing the pattern of atherosclerosis observed in recent years, also requires the introduction of new approaches in the prevention of atherosclerosis, enhancing the protection of the endothelium. This review focuses on the research, covering the role of hemostasis in the pathogenesis of atherosclerosis.

Hemostasis disorders in preterm infants occur more often than in full-term ones due to the immaturity of the coagulation system, and lead to the appearance of hemorrhagic syndrome [1, 2]. Various forms of blood coagulation disorders in newborns can be both primary, with independent nosological significance, and secondary, if they are an intermediate link in the pathogenesis of many serious diseases and processes, significantly affecting the course and outcomes, making the main pathogenetic therapy ineffective [3]. Monitoring of hemostasis indices is necessary both timely assessment and preclinical diagnosis of hemorrhagic and thrombotic manifestations, and for evaluating the effectiveness of treatment. To assess such deviations, it is necessary to know the normative indicators of hemostasis, which are determined for full-term, but to a lesser extent - for premature infants. Of particular importance for the correct assessment of hemostatic disorders is the knowledge of the characteristics of changes in hemostasiological parameters in the dynamics of the early neonatal period. Currently, they defined for full-term [4, 5] and to a lesser extent for premature newborns [6]. Currently, there are no comprehensive data on hemostasis in preterm infants performed on modern analytical systems, and therefore the goal of this work was to refine the characteristics of plasma hemostasis in preterm infants taking into account their gestational age (GA). [ABSTRACT FROM AUTHOR]

Systemic therapeutic hypothermia has gained a negative reputation in treating multiple trauma patients and is regarded as one of the factors in the lethal triad of shock, acidosis, and hypothermia. This fact owes to no relationship between acidosis and hypothermia; the effects of the latter on coagulation are evident and complexly reversible in the presence of acidosis.Objective: to determine the impact of noninvasive local brain cooling on the metabolic and blood coagulation indicators of a patient with acute cerebral ischemia.Subjects and methods. The subjects of the study were 113 patients with severe brain injury, including that complicated by the involvement of stem structures, who underwent brain cooling in different modifications. In so doing, the val ues of acidbase balance and coagulation system in arterial and venous blood were investigated.Results. Local brain hypother mia was not found to affect coagulation while the baseline negative values of excess buffer bases showed positive values (a right shift) by the end of cooling. Recommendations were given to prevent metabolic shifts.Conclusion. Patients at very high risk for bleeding may be safely cooled to a brain temperature of 32—34°C even in the presence of moderatetosevere acidosis. This is a great advantage of local hypothermia over systemic one.

Haemostasis is a set of processes with the aim to maintain blood in the liquid state in the vascular bed, and in the case of damage to the vessel – to prevent extravasation by clot formation (initially a platelet clot and then a fibrin clot). The main components of haemostasis include: platelets, vessel wall, plasma coagulation system, endogenous inhibitors of coagulation and fibrinolytic system. The stream of blood is also an important factor. Haemostasis is divided into two main phases: coagulation and fibrinolysis. These two phases take place simultaneously and remain in equilibrium. The prevalence of any of these processes is the result of the advantage of enzyme complex activity over the complex of the other process. In everyday practice, every physician encounters drugs that affect haemostasis. At the end of the article, the most commonly used anticoagulants and antiplatelet agents available in Poland are described with the mechanisms of their action. The effect of oral anticoagulants results from the inhibition of the transformation of vitamin K1 which is essential for the production of coagulation factors II, VII, IX and X. Acenocoumarol and warfarin are currently available in Poland. The group of new oral anticoagulants includes direct inhibitors of activated factor X: rivaroxaban, apixaban and dabigatran – a potent, competitive and reversible direct thrombin inhibitor. Anticoagulants which are used parenterally include unfractionated heparin, low molecular weight heparins and fondaparinux. Antiplatelet drugs can be divided into two groups based on the mechanism of action – drugs acting through the metabolism of arachidonic acid (aspirin) and acting on the platelet membrane receptors (ticlopidine, clopidogrel and prasugrel).

Background: Blood flow restriction (BFR) exercise has shown to induce a positive influence on bone metabolism and attenuate muscle strength loss and atrophy in subjects suffering from musculoskeletal weakness. Despite the known benefits of BFR exercise, it remains unclear whether or not the pressurization of blood vessels damages the endothelial cells or increases risk for formation of thrombi. Thus, the effects of BFR exercise on coagulation, fibrinolysis, or hemostasis, remains speculative. Objective: The aim of the present study was to perform a systematic review of the short and long- term effects of BFR exercise on blood hemostasis in healthy individuals and patients with known disease (ie, hypertension, diabetes, obesity, and ischemic heart disease). Data Sources: A systematic review of English and non-English articles was conducted across PubMed, Science Direct, and Google Scholar databases, including reference lists of relevant papers. Study quality assessment was evaluated using the modified version of Downs and Black checklist. Search results were limited to exercise training studies investigating the effects of BFR exercise on blood hemostasis in healthy individuals and patients with disease. Level of evidence was determined according to the criteria described by Oxford Center for Evidence-Based Medicine.  Study selection: Only randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) that examined the effects of exercise with BFR exercise vs exercises without BFR on blood hemostasis in healthy individuals and patients were included. Data extraction: Nine studies were eligible (RCT =4; NRCT =5). Results: The average score on the Downs and Black checklist was 11.22. All studies were classified as having poor methodological quality wherein the level of evidence provided in all reviewed studies was level IIb only (ie, poor quality RCTs). Conclusion: Considering the limitations in the available evidence, firm recommendations cannot be provided. [ABSTRACT FROM AUTHOR]