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Coagulation pathways

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https://www.readbyqxmd.com/read/28640782/perioperative-venous-thromboembolism-a-review
#1
Ronald J Gordon, Frederick W Lombard
Venous thromboembolism (VTE) is a significant problem in the perioperative period, increasing patient morbidity, mortality, and health care costs. It is also considered the most preventable of the major postoperative complications. Despite widespread adoption of prophylaxis guidelines, it appears that morbidity from the disease has not substantially changed within the past 2 decades. It is becoming clear that current prophylaxis efforts are not sufficient. Using more potent anticoagulants may decrease the incidence of VTE, but increase the risk for bleeding and infection...
June 20, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28637314/dna-methylation-signatures-and-coagulation-factors-in-the-peripheral-blood-leucocytes-of-epithelial-ovarian-cancer
#2
Lian Li, Hong Zheng, Yubei Huang, Caiyun Huang, Shuang Zhang, Jing Tian, Pei Li, Anil K Sood, Wei Zhang, Kexin Chen
Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins, and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485,000 CpG sites in peripheral blood in 24 epithelial ovarian cancer cases and 24 age-matched healthy controls...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28634578/neonatal-venous-thromboembolism
#3
REVIEW
Kristina M Haley
Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE), and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#4
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632510/itraq-based-quantitative-proteomic-analysis-of-lungs-in-murine-polymicrobial-sepsis-with-hydrogen-gas-treatment
#5
Yingxue Bian, Chao Qin, Yuchang Xin, Yang Yu, Hongguang Chen, Guolin Wang, Keliang Xie, Yonghao Yu
Sepsis-associated acute lung injury (ALI), which carries a high morbidity and mortality in patients, has no effective therapeutic strategies to date. Our group have already reported that hydrogen gas (H2) exerts a protective effect against sepsis in mice. However, the molecular mechanisms underlying H2 treatment are not fully understood. This study investigated the effects of H2 on lung injuries in septic mice through the iTRAQ-based quantitative proteomic analysis. Male ICR mice used in this study were subjected to cecal ligation and puncture (CLP) or sham operation...
June 19, 2017: Shock
https://www.readbyqxmd.com/read/28614247/meld-score-as-a-predictor-of-mortality-length-of-hospital-stay-and-disease-burden-a-single-center-retrospective-study-in-39-323-inpatients
#6
Jan A Roth, Carl Chrobak, Sabine Schädelin, Balthasar L Hug
The laboratory-based model for end-stage liver disease (MELD) score reflects the function of the kidney, liver, and extrinsic coagulation pathway and might be used as a general prognostic tool for the assessment of patients. We therefore aimed to investigate a potential association of the MELD score with mortality, length of hospital stay (LOS), and disease burden in a general patient population.We performed a retrospective observational study at a tertiary referral center. From January 2012 through December 2013, all consecutive inpatients aged 18 years were eligible for the study; patients with missing MELD parameters on hospital admission and/or treatments influencing the international normalized ratio, that is, novel oral anticoagulants and vitamin K antagonists, were excluded...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28614056/spermine-and-spermidine-reversed-age-related-cardiac-deterioration-in-rats
#7
Hao Zhang, Junying Wang, Lingxu Li, Nannan Chai, Yuhan Chen, Feixiang Wu, Weihua Zhang, Lina Wang, Sa Shi, Li Zhang, Shuling Bian, Changqing Xu, Ye Tian, Yajun Zhao
Aging is the most important risk factor for cardiovascular disease (CVD). Slowing or reversing the physiological impact of heart aging may reduce morbidity and mortality associated with age-related CVD. The polyamines, spermine (SP) and spermidine (SPD) are essential for cell growth, differentiation and apoptosis, and levels of both decline with age. To explore the effects of these polyamines on heart aging, we administered SP or SPD intraperitoneally to 22- to 24-month-old rats for 6 weeks. Both treatments reversed and inhibited age-related myocardial morphology alterations, myocardial fibrosis, and cell apoptosis...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612396/diagnosis-of-inherited-bleeding-disorders-in-the-genomic-era
#8
REVIEW
Suthesh Sivapalaratnam, Janine Collins, Keith Gomez
Inherited bleeding disorders affect between 1 in 1000 individuals for the most common disorder, von Willebrand Disease, to only 8 reported cases worldwide of alpha-2-antiplasmin deficiency. Those with an identifiable abnormality can be divided into disorders of coagulation factors (87%), platelet count and function (8%) and the fibrinolytic system (3%). Of the patients registered in the UK with a bleeding disorder, the remaining 2% are unclassifiable. In addition to bleeding symptoms, patients with an inherited bleeding disorder can manifest other abnormalities, making an accurate and complete diagnosis that reflects the underlying molecular pathology important...
June 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28606852/new-prodrugs-of-metformin-do-not-influence-the-overall-haemostasis-potential-and-integrity-of-the-erythrocyte-membrane
#9
Magdalena Markowicz-Piasecka, Joanna Sikora, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Although metformin, an oral anti-diabetic drug, has been found to have multidirectional effects over the past decade, it is characterised by unfavourable pharmacokinetic properties. This study discusses the effects of metformin, phenformin and three prodrugs of metformin on the haemostasis and integrity of Red Blood Cells (RBCs). The influence of examined biguanide derivatives on haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test) at 405 nm. The extrinsic and intrinsic coagulation pathway were examined by measuring the PT (Prothrombin Time) and aPTT (Activated Partial Tromboplastin Time)...
June 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28604360/chitosan-based-hydrogels-for-developing-a-small-diameter-vascular-graft-in-vitro-and-in-vivo-evaluation
#10
Audrey Aussel, Noélie Thébaud, Xavier Berard, Vincenzo Brizzi, Samantha Delmond, Reine Bareille, Robin Siadous, Chloe James, Jean Ripoche, Marlène Durand, Alexandra Montembault, Béatrice Burdin, Didier Letourneur, Nicolas L'Heureux, Laurent David, Laurence Bordenave
Vascular grafts made of synthetic polymers perform poorly in small-diameter applications (cardiac and peripheral bypass). Chitosan is a biocompatible natural polymer that can provide a novel biological scaffold for tissue engineering development. The goal of this study was to demonstrate the biocompatibility of a novel chitosan preparation in vitro and in vivo, and to assess its potential as a scaffold for vascular applications. Methods and Results. A series of experiments of increasing complexity, ranging from in vitro biocompatibility and hemocompatibility tests to in vivo studies in small and large animals (rat and sheep), was performed to provide a comprehensive analysis of chitosan hydrogels' biological properties...
June 12, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28601907/high-glucose-increases-the-formation-and-pro-oxidative-activity-of-endothelial-microparticles
#11
Dylan Burger, Maddison Turner, Fengxia Xiao, Mercedes N Munkonda, Shareef Akbari, Kevin D Burns
AIMS/HYPOTHESIS: Individuals with diabetes exhibit increases in circulating endothelial microparticles (eMPs, also referred to as endothelial microvesicles), which are associated with endothelial dysfunction and a heightened risk of cardiovascular complications. We have shown that eMPs are markers and mediators of vascular injury although their role in diabetes is unclear. We hypothesised that the composition and biological activity of eMPs are altered in response to high glucose exposure...
June 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28595568/differences-in-responses-of-grass-carp-to-different-types-of-grass-carp-reovirus-gcrv-and-the-mechanism-of-hemorrhage-revealed-by-transcriptome-sequencing
#12
Libo He, Aidi Zhang, Yongyan Pei, Pengfei Chu, Yongming Li, Rong Huang, Lanjie Liao, Zuoyan Zhu, Yaping Wang
BACKGROUND: Grass carp is an important farmed fish in China that is affected by serious disease, especially hemorrhagic disease caused by grass carp reovirus (GCRV). The mechanism underlying the hemorrhagic symptoms in infected fish remains to be elucidated. Although GCRV can be divided into three distinct subtypes, differences in the pathogenesis and host immune responses to the different subtypes are still unclear. The aim of this study was to provide a comprehensive insight into the grass carp response to different GCRV subtypes and to elucidate the mechanism underlying the hemorrhagic symptoms...
June 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28594458/concizumab-an-anti-tissue-factor-pathway-inhibitor-antibody-induces-increased-thrombin-generation-in-plasma-from-haemophilia-patients-and-healthy-subjects-measured-by-the-thrombin-generation-assay
#13
E K Waters, J Sigh, U Friedrich, I Hilden, B B Sørensen
AIMS: Concizumab, a humanized monoclonal antibody against tissue factor pathway inhibitor (TFPI), is being developed as a subcutaneously (s.c.) administered treatment for haemophilia. It demonstrated a concentration-dependent procoagulant effect in functional TFPI assays; however, global haemostatic assays, such as the thrombin generation assay (TGA), offer a more complete picture of coagulation. We investigated how concizumab affects thrombin generation following ex vivo spiking in plasma from haemophilia patients using the TGA, and if the assay can detect the effect of multiple s...
June 8, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28594052/coagulation-factor-and-protease-pathways-in-thrombosis-and-cardiovascular-disease
#14
Hugo Ten Cate, Tilman M Hackeng, Pablo García de Frutos
The biochemical characterization of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during the second half of the 20th century. Understanding these pathways was of crucial importance for improving global health through application in haemostasis and thrombosis pathologies. Immediately after the cloning of the genes corresponding to these proteins, mutations were discovered in them that were associated with imbalances in haemostasis...
June 8, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28593875/intrauterine-growth-restriction-and-placental-gene-expression-in-severe-preeclampsia-comparing-early-onset-and-late-onset-forms
#15
Jaana Nevalainen, Sini Skarp, Eeva-Riitta Savolainen, Markku Ryynänen, Jouko Järvenpää
OBJECTIVE: To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. STUDY DESIGN: Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. RESULTS: Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia...
April 13, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28589128/low-density-lipoprotein-receptor-related-protein-1-signaling-in-angiogenesis
#16
REVIEW
Hua Mao, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer's disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28587383/mechanism-of-the-protective-effects-of-the-combined-treatment-with-rhynchophylla-total-alkaloids-and-sinapine-thiocyanate-against-a-prothrombotic-state-caused-by-vascular-endothelial-cell-inflammatory-damage
#17
Yunlun Li, Xinya Zhang, Wenqing Yang, Chao Li, Yanjun Chu, Haiqiang Jiang, Zhenzhen Shen
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28583531/does-activated-clotting-time-help-to-predict-innate-coagulopathy-in-end-stage-liver-disease-patients
#18
H-W Jeong, H-M Kwon, K-W Jung, Y-J Moon, I-G Jun, J-G Song, G-S Hwang
BACKGROUND: Measuring activated clotting time (ACT) is widely performed to monitor heparin therapy. Regardless of anticoagulant use, ACT is affected by coagulopathies such as coagulation factor deficiency and thrombocytopenia. However, its use in end-stage liver disease (ESLD) with complex coagulopathy is not well characterized. We evaluated whether ACT could be used to detect innate coagulopathy in ESLD patients. METHODS: We retrospectively assessed Hemochron (International Technidyne, Edison, NJ, USA) ACT (FTCA 510, normal range 105-167 seconds) and INTEM clotting time (CT) of rotational thromboelastometry (ROTEM; ROTEM delta, Pentapharm GmbH, Munich, Germany) (100-240 seconds) in 366 liver transplantation (LT) recipients, simultaneously measured before anesthetic induction for LT...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28580443/reduced-prothrombinase-inhibition-by-tissue-factor-pathway-inhibitor-contributes-to-the-factor-v-leiden-hypercoagulable-state
#19
Jeremy P Wood, Lisa M Baumann Kreuziger, Paul E R Ellery, Susan A Maroney, Alan E Mast
Activated factor V (FVa) and factor X (FXa) form prothrombinase, which converts prothrombin to thrombin. The α isoform of tissue factor (TF) pathway inhibitor (TFPI) dampens early procoagulant events, partly by interacting with FV. FV Leiden (FVL) is the most common genetic thrombophilia in Caucasians. Thrombosis risk is particularly elevated in women with FVL taking oral contraceptives, which produce acquired TFPIα deficiency. In mice, FVL combined with 50% reduction in TFPI causes severe thrombosis and perinatal lethality...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28580033/dynamics-of-blood-flow-and-thrombus-formation-in-a-multi-bypass-microfluidic-ladder-network
#20
Jevgenia Zilberman-Rudenko, Joanna L Sylman, Hari H S Lakshmanan, Owen J T McCarty, Jeevan Maddala
The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL...
February 2017: Cellular and Molecular Bioengineering
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