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Clotting cascade

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https://www.readbyqxmd.com/read/28225379/the-presentation-of-a-fussy-infant-with-bruising-late-onset-vitamin-k-deficiency-bleeding
#1
Katherine Wolpert, Matthew Szadkowski, Michael Miescier, Hilary A Hewes
Vitamin K plays an integral role in the clotting cascade. Deficiency, specifically in vulnerable neonates with insufficient stores, can lead to spontaneous bleeding and devastating effects. In this case, we report a young infant with late-onset vitamin K deficiency bleeding who did not receive vitamin K prophylaxis after birth. Initially presenting with bruising and fussiness, the patient was later found to have intracerebral hemorrhage with midline shift and uncal herniation. The infant was not a surgical candidate and died shortly thereafter...
February 21, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28223350/mapping-atheroprotective-functions-and-related-proteins-lipoproteins-in-size-fractionated-human-plasma
#2
Debi K Swertfeger, Hailong Li, Sandra Rebholz, Xiaoting Zhu, Amy S Shah, W Sean Davidson, L Jason Lu
HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS)...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223279/distinct-contributions-of-complement-factors-to-platelet-activation-and-fibrin-formation-in-venous-thrombus-development
#3
Saravanan Subramaniam, Kerstin Jurk, Lukas Hobohm, Sven Jäckel, Mona Saffarzadeh, Kathrin Schwierczek, Philip Wenzel, Florian Langer, Christoph Reinhardt, Wolfram Ruf
Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity and the coagulation and complement cascades. Here we show in a tissue factor (TF)-dependent model of flow restriction-induced venous thrombosis that complement factors (C) make distinct contributions to platelet activation and fibrin deposition. C3-deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28213103/expression-and-characterization-of-haemathrins-madanin-like-thrombin-inhibitors-isolated-from-the-salivary-gland-of-tick-haemaphysalis-bispinosa-acari-ixodidae
#4
Rajeev Kungur Brahma, Guillaume Blanchet, Simran Kaur, R Manjunatha Kini, Robin Doley
Saliva of hematophagous animals, such as ticks, is an excellent source of anticoagulant proteins and polypeptides. Here we describe the identification and characterization of two thrombin inhibitors named as haemathrin 1 and 2 from the salivary gland of tick Haemaphysalis bispinosa using genomic approach. Haemathrins are cysteine-less peptide anticoagulants, which share about 65-70% identity with madanins, and belong to inhibitor I53 superfamily of inhibitors of the MEROPS database. Haemathrins were overexpressed in E...
January 31, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28176468/correlation-of-pre-operative-plasma-protein-concentrations-in-cardiac-surgery-patients-with-bleeding-outcomes-using-a-targeted-quantitative-proteomics-approach
#5
Nathan Clendenen, Ashley Tollefson, Monika Dzieciatkowska, Alice Cambiaghi, Manuela Ferrario, Miranda Kroehl, Anirban Banerjee, Angelo D'Alessandro, Kirk C Hansen, Nathaen Weitzel
PURPOSE: Despite recent advancements in the use of thrombelastography (TEG) in the surgical setting, adequate technology to accurately predict bleeding phenotypes for patients undergoing cardiopulmonary bypass on the basis of non-mechanical parameters is lacking. While basic science and translational studies have provided key mechanistic insights about the protein components of coagulation cascades and regulatory mediators of hemostasis and fibrinolysis, targeted protein assays are still missing and the association of protein profiles to bleeding phenotypes and TEG readouts have yet to be discovered...
February 8, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28120727/antiplatelet-agents-and-anticoagulants-from-pharmacology-to-clinical-practice
#6
Maria E Tsoumani, Alexandros D Tselepis
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28089408/the-various-assays-for-measuring-activity-states-of-factor-viia-in-plasma-and-therapeutic-products-diagnostic-value-and-analytical-usefulness-in-various-pathophysiological-states
#7
REVIEW
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms...
December 29, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28079789/the-impact-of-irrigating-fluid-absorption-on-blood-coagulation-in-patients-undergoing-transurethral-resection-of-the-prostate-a-prospective-observational-study-using-rotational-thromboelastometry
#8
Hyun-Jung Shin, Hyo-Seok Na, Young-Tae Jeon, Hee-Pyoung Park, Sun-Woo Nam, Jung-Won Hwang
Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28035951/a-systematic-review-of-the-role-of-dysfunctional-wound-healing-in-the-pathogenesis-and-treatment-of-idiopathic-pulmonary-fibrosis
#9
REVIEW
Alan Betensley, Rabab Sharif, Dimitrios Karamichos
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments...
December 26, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#10
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28005926/the-central-role-of-kng1-gene-as-a-genetic-determinant-of-coagulation-pathway-related-traits-exploring-metaphenotypes
#11
Helena Brunel, Raimon Massanet, Angel Martinez-Perez, Andrey Ziyatdinov, Laura Martin-Fernandez, Juan Carlos Souto, Alexandre Perera, José Manuel Soria
Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i...
2016: PloS One
https://www.readbyqxmd.com/read/27994741/discovery-of-phenylglycine-lactams-as-potent-neutral-factor-viia-inhibitors
#12
Nicholas R Wurtz, Brandon L Parkhurst, Wen Jiang, Indawati DeLucca, Xiaojun Zhang, Vladimir Ladziata, Daniel L Cheney, Jeffrey R Bozarth, Alan R Rendina, Anzhi Wei, Joseph M Luettgen, Yiming Wu, Pancras C Wong, Dietmar A Seiffert, Ruth R Wexler, E Scott Priestley
Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27942785/-factor%C3%A2-xiii-pharmacodynamic-and-pharmacokinetic-characteristics
#13
E H Adam, S Kreuer, K Zacharowski, C F Weber, R Wildenauer
Factor XIII (FXIII) plays an important role in the field of blood coagulation. In the last decade, both congenital and acquired deficiencies have been investigated in clinical studies. FXIII is a versatile enzyme that leads to a covalent cross-linking of fibrin fibrils at the end of the clotting cascade and supports platelet adhesion to the damaged sub-endothelium with the result of a mechanically stable clot.Symptoms of FXIII deficiencies vary within a broad spectrum from superficial skin bleeding episodes to severe, sometimes life threatening hemorrhage, requiring prophylactic or therapeutic replacement therapy...
January 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/27928886/f376a-m388a-solulin-a-new-promising-antifibrinolytic-for-severe-haemophilia-a
#14
J Parcq, K U Petersen, A Borel-Derlon, P Gautier, M Ebel, D Vivien, Y Repessé
INTRODUCTION: Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics...
December 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27906868/individual-clotting-factor-contributions-to-mortality-following-trauma
#15
Ryan C Kunitake, Benjamin M Howard, Lucy Z Kornblith, Sabrinah A Christie, Amanda S Conroy, Mitchell J Cohen, Rachael A Callcut
BACKGROUND: Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. METHODS: This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015...
February 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27885044/blood-clotting-behavior-is-innately-modulated-in-ursus-americanus-during-early-and-late-denning-relative-to-summer-months
#16
Tinen L Iles, Timothy G Laske, David L Garshelis, Paul A Iaizzo
Remarkably, American black bears (Ursus Americanus) are capable of varying their heart rates to coincide with their breathing, creating pauses of 30 seconds or more, yet they do not appear to suffer from embolic events. We evaluated some features of the clotting cascade of black bears, providing novel insights on the underlying mechanisms they evoke for embolic protection during hibernation.We measured activated clotting times, prothrombin times, and activated partial thromboplastin times during early-denning (December), late-denning (March), and summer (August)...
November 24, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27824218/coagulopathy-in-sepsis-a-new-look-at-an-old-problem
#17
Małgorzata Lipinska-Gediga
Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis...
2016: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/27822142/non-enzymatic-upregulation-of-tissue-factor-expression-by-gamma-glutamyl-transferase-in-human-peripheral-blood-mononuclear-cells
#18
Valentina Scalise, Cristina Balia, Silvana Cianchetti, Tommaso Neri, Vittoria Carnicelli, Riccardo Zucchi, Maria Franzini, Alessandro Corti, Aldo Paolicchi, Alessandro Celi, Roberto Pedrinelli
BACKGROUND: Besides maintaining intracellular glutathione stores, gamma-glutamyltransferase(GGT) generates reactive oxygen species and activates NFkB, a redox-sensitive transcription factor key in the induction of Tissue Factor (TF) gene expression, the principal initiator of the clotting cascade. Thus, GGT might be involved in TF-mediated coagulation processes, an assumption untested insofar. METHODS: Experiments were run with either equine, enzymatically active GGT or human recombinant (hr) GGT, a wheat germ-derived protein enzymatically inert because of missing post-translational glycosylation...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27818307/hemocompatibility-studies-on-a-degradable-polar-hydrophobic-ionic-polyurethane-d-phi
#19
Kathryne S Brockman, Jayachandran N Kizhakkedathu, J Paul Santerre
: Biomaterial blood compatibility is a complex process that involves four key pathways, including the coagulation cascade, the complement system, platelets, and leukocytes. While many studies have addressed the initial contact of blood with homopolymeric (e.g. Teflon) or simple copolymeric (e.g. Dacron) biomaterials, relatively less attention has been given to investigating blood coagulation with respect to complex copolymeric systems containing well defined and diverse function. The current study sought to assess the hemocompatibility of a complex polyurethane (PU) containing a unique combination of polar, hydrophobic, and ionic domains (D-PHI)...
November 3, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27804204/assessing-the-contact-activation-of-coagulation-during-hemodialysis-with-three-different-polysulfone-filters-a-prospective-randomized-cross-over-trial
#20
Igor Salvadè, Rosaria Del Giorno, Donato Gaetano, Luca Gabutti
Introduction During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D-dimers in the filter-rinsing fluids (Frf) and to test whether Frf D-dimers are suitable candidate markers to assess contact coagulation activation during HD...
November 1, 2016: Hemodialysis International
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