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Coagulation pathways

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https://www.readbyqxmd.com/read/28726538/marked-bleeding-diathesis-in-patients-with-platelet-dysfunction-due-to-a-novel-mutation-in-rasgrp2-encoding-caldag-gefi-p-gly305asp
#1
Emilse Bermejo, Maria F Alberto, David S Paul, Aaron A Cook, Paquita Nurden, Analia Sanchez Luceros, Alan T Nurden, Wolfgang Bergmeier
Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28716211/to-serve-and-protect-the-modulatory-role-of-von-willebrand-factor-on-factor-viii-immunogenicity
#2
REVIEW
Robin B Hartholt, Alice S van Velzen, Ivan Peyron, Anja Ten Brinke, Karin Fijnvandraat, Jan Voorberg
Hemophilia A is a bleeding disorder characterized by the absence or dysfunction of blood coagulation factor VIII (FVIII). Patients are treated with regular infusions of FVIII concentrate. In response to treatment, approximately 30% of patients with severe hemophilia A develop inhibitory antibodies targeting FVIII. Both patient and treatment related risk factors for inhibitor development have been described. Multiple studies comparing the immunogenicity of recombinant and plasma-derived FVIII have yielded conflicting results...
July 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28716011/association-study-to-evaluate-tfpi-gene-in-cad-in-han-chinese
#3
Ying Zhao, Yanbo Yu, Maowei Shi, Xi Yang, Xueqi Li, Feng Jiang, Yundai Chen, Xiaoli Tian
BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. This study was designed to determine whether the variation of TFPI was related with coronary artery disease (CAD) in the Han Chinese populations. METHODS: A total of 1271 patients with coronary atherosclerosis and 1287 normal individuals from northern China were enrolled in the present study...
July 17, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28713160/pathogenic-roles-of-microvesicles-in-diabetic-retinopathy
#4
REVIEW
Wei Zhang, Song Chen, Ming-Lin Liu
Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNAs, transcription factors, membrane lipids, membrane receptors, and other proteins. They may be involved in intercellular communication that can promote inflammation, angiogenesis, and coagulation...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28711159/-hemolytic-and-uremic-syndrome-and-related-thrombotic-microangiopathies-epidemiology-pathophysiology-and-clinics
#5
C Rafat, P Coppo, F Fakhouri, V Frémeaux-Bacchi, C Loirat, J Zuber, E Rondeau
Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature...
July 12, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28705781/effects-of-interleukin-17-on-the-cardiovascular-system
#6
REVIEW
Marie Robert, Pierre Miossec
Cardiovascular diseases remain the leading cause of death worldwide and account for most of the premature mortality observed in chronic inflammatory diseases. Common mechanisms underlie these two types of disorders, where the contribution of Interleukin (IL)-17A, the founding member of the IL-17 family, is highly suspected. While the local effects of IL-17A in inflammatory disorders have been well described, those on the cardiovascular system remain less studied. This review focuses on the effects of IL-17 on the cardiovascular system both on isolated cells and in vivo...
July 10, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28698122/transcriptome-analysis-and-discovery-of-genes-involved-in-immune-pathways-in-large-yellow-croaker-larimichthys-crocea-under-high-stocking-density-stress
#7
Peng Sun, Peibo Bao, Baojun Tang
The large yellow croaker, Larimichthys crocea, is an economically important maricultured species in southeast China. Owing to the importance of stocking densities in commercial fish production, it is crucial to establish the physiological responses and molecular mechanisms that govern adaptation to crowding in order to optimize welfare and health. In the present study, an extensive immunity-related analysis was performed at the transcriptome level in L. crocea in response to crowding stress. Over 145 million high-quality reads were generated and de novo assembled into a final set of 40,123 unigenes...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28694452/phosphatidylserine-mediated-platelet-clearance-by-endothelium-decreases-platelet-aggregates-and-procoagulant-activity-in-sepsis
#8
Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692431/differing-mechanisms-of-thrombin-generation-in-live-haematological-and-solid-cancer-cells-determined-by-calibrated-automated-thrombography
#9
Mufuliat Adeola Adesanya, Anthony Maraveyas, Leigh Madden
: Calibrated automated thrombography (CAT) is emerging as a reliable tool for real-time estimation of thrombin generation potential. There is a clinical need for knowledge about the pathways underlying the thrombotic phenotype of different malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for thrombin generation, using CAT, with the addition of control plasma (NormTrol; Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors VII and XII...
July 7, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28688220/assessment-of-the-protein-interaction-between-coagulation-factor-xii-and-corn-trypsin-inhibitor-by-molecular-docking-and-biochemical-validation
#10
Badraldin K Hamad, Monika Pathak, Rosa Manna, Peter M Fischer, Jonas Emsley, Lodewijk V Dekker
BACKGROUND: Corn trypsin inhibitor (CTI) has selectivity for serine proteases coagulation factor XII (FXII) and trypsin. CTI is in widespread use as a reagent that specifically inhibits the intrinsic pathway of blood coagulation but not the extrinsic pathway. OBJECTIVES: To investigate the molecular basis of FXII inhibition by CTI. METHODS: We performed molecular docking of CTI, using its known crystal structure, with a model of the activated FXII (FXIIa) protease domain...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28687614/signal-integration-at-the-pi3k-p85-xbp1-hub-endows-coagulation-protease-activated-protein-c-with-insulin-like-function
#11
Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J Müller, Charles T Esmon, Peter P Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling both impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER)-homeostasis. Analogous to insulin, physiological levels of aPC maintain endoplasmic reticulum (ER) proteostasis in DKD...
July 7, 2017: Blood
https://www.readbyqxmd.com/read/28687347/hestat-study-protocol-for-a-phase-ii-iii-randomized-placebo-controlled-single-blind-study-to-evaluate-the-new-hemostatic-agent-tt-173-in-total-knee-arthroplasty
#12
Aránzazu Gonzalez-Osuna, Sebastián Videla, Esther Cánovas, Gerard Urrútia, Santiago Rojas, Ramón López, Jesús Murat, Xavier Aguilera
BACKGROUND: Total knee arthroplasty is associated with postsurgical bleeding that often requires blood transfusion. Several hemostatic treatments have been evaluated with different degree of success. TT-173 is a topical hemostatic agent consisting in yeast derived vesicles containing recombinant tissue factor (rhFT) that activates the extrinsic pathway of coagulation. This trial sought to evaluate the efficacy and safety of TT-173 in total knee arthroplasty. METHODS/DESIGN: This is a phase II/III, sequential, simple blind, randomized, multicenter, placebo controlled and parallel clinical trial that will recruit 189 evaluable patients...
July 4, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28687020/chemotherapy-administration-to-breast-cancer-patients-affects-extracellular-vesicles-thrombogenicity-and-function
#13
Anat Aharon, Anni Sabbah, Shahar Ben-Shaul, Hila Berkovich, David Loven, Benjamin Brenner, Gil Bar-Sela
Breast cancer (BC) is the most prevalent type of malignancy in women. Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles. STUDY AIMS: To elucidate the effects of chemotherapy administration on BC patients' EVs characteristics and their effects on endothelial cells (EC) functions. METHODS: EVs were isolated from the blood samples of 54 BC patients treated by chemotherapy (25 neo-adjuvant, 29 adjuvant) and from 20 healthy women (control group)...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28681388/mmp9-is-decreased-in-natalizumab-treated-ms-patients-at-risk-for-pml
#14
Nicolas Fissolo, Béatrice Pignolet, Clara Matute-Blanch, Juan Carlos Triviño, Berta Miró, Miriam Mota, Santiago Perez-Hoyos, Alex Sanchez, Patrick Vermersch, Aurélie Ruet, Jérome de Sèze, Pierre Labauge, Sandra Vukusic, Caroline Papeix, Laurent Almoyna, Ayman Tourbah, Pierre Clavelou, Thibault Moreau, Jean Pelletier, Christine Lebrun-Frenay, Xavier Montalban, David Brassat, Manuel Comabella
OBJECTIVE: To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ). METHODS: Relapsing-remitting MS (RRMS) patients who developed PML under NTZ therapy (pre-PML) and non-PML natalizumab-treated patients (NTZ-ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells (PBMC) and serum samples collected at baseline, at one- and two-year treated time points, and during PML were analyzed for gene expression by RNA-sequencing and for serum protein levels by LUMINEX and ELISA assays respectively...
July 6, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28677246/factor-xi-deficient-mice-exhibit-increased-bleeding-after-injury-to-the-saphenous-vein
#15
C Ay, Y Hisada, B Cooley, N Mackman
BACKGROUND: Factor XI (FXI) is a key component of the intrinsic pathway of coagulation. It can be activated by either FXIIa or thrombin and amplifies thrombin generation during clot formation. Congenital FXI deficiency in humans (known as hemophilia C) is associated with bleeding after hemostatic challenge. However, to date there are no reports of excess bleeding in FXI deficient mice. OBJECTIVES: To determine if the absence of FXI in mice prolongs bleeding in different models...
July 4, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28672899/pathway-related-modules-involved-in-the-application-of-sevoflurane-or-propofol-in-off-pump-coronary-artery-bypass-graft-surgery
#16
Xiangmei Bu, Bo Wang, Yaoqi Wang, Zhigang Wang, Chunzhi Gong, Feng Qi, Caixia Zhang
Off-pump coronary artery bypass graft (CABG) surgery has recently emerged as a means to avoid the sequelae of extracorporeal circulation, including the whole-body inflammatory response, coagulation disorders and multiple organ dysfunction. At present, gas anesthesia, sevoflurane and intravenous anesthesia and propofol have been widely used during the CABG. To further understand the underlying mechanisms of these anesthetics on the gene level, the present study conducted pathway-related module analysis based on a co-expression network...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28671348/novel-insights-into-the-regulation-of-coagulation-by-factor-v-isoforms-tissue-factor-pathway-inhibitor%C3%AE-and-protein-s
#17
B Dahlbäck
Factor V (FV) is a regulator of both pro- and anticoagulant pathways. It circulates as a single-chain procofactor, which is activated by thrombin or FXa to FVa that serves as cofactor for FXa in prothrombin activation. The cofactor function of FVa is regulated by activated protein C (APC) and protein S. FV can also function as an anticoagulant APC cofactor in the inhibition of FVIIIa in the membrane-bound tenase complex (FIXa/FVIIIa). In recent years, it has become clear that FV also functions in multiple ways in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway...
July 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28669628/role-of-oxidative-stress-in-cardiovascular-disease-outcomes-following-exposure-to-ambient-air-pollution
#18
REVIEW
Frank J Kelly, Julia C Fussell
Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28663071/outside-in-inside-out-proteomic-analysis-of-endothelial-stress-mediated-by-7-ketocholesterol
#19
Lívia Rosa-Fernandes, Luciana M F Maselli, Nair Y Maeda, Giuseppe Palmisano G, Sergio P Bydlowski
Oxysterols are cholesterol oxidation products formed through enzymatic or autoxidation mechanisms. 7-ketocholeterol (7KC) is one of most abundant oxysterols found in atherosclerotic lesions. Its role in atherosclerosis pathogenesis has been broadly studied in a variety of models. The arterial microenvironment is a multicellular dynamic compartment that, among other systemic factors, is continuously stimulated by 7KC. Endothelial cells have a key role on that environment, being in intimate contact with both the blood stream and the vessel wall, the site of disease origin...
June 26, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#20
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
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