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thrombin generation

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https://www.readbyqxmd.com/read/28821129/characterization-and-anticoagulant-activity-of-a-fucosylated-chondroitin-sulfate-with-unusually-procoagulant-effect-from-sea-cucumber
#1
Mohamed Ben Mansour, Rafik Balti, Véronique Ollivier, Hichem Ben Jannet, Frédéric Chaubet, Raoui Mounir Maaroufi
The fucosylated chondroitin sulfate (FuCS) was isolated from the sea cucumber Holothuria polii body wall and then purified by anion exchange chromatography and the structure was characterized by FT-IR and NMR spectroscopy. Anticoagulant activity was measured in plasma by classical anticoagulation tests and the thrombin generation was assessed by calibrated automated thrombography. The results showed that the FuCS obtained at a yield of 4.66% possesses high sulfate content 43% and an average molecular mass of 45...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820747/involvement-of-hyperglycemia-in-the-development-of-platelet-procoagulant-response-the-role-of-aldose-reductase-and-platelet-swelling
#2
Tomasz Rusak, Tomasz Misztal, Malgorzata Rusak, Justyna Branska-Januszewska, Marian Tomasiak
: Rise in mean platelet volume (MPV) has been demonstrated to be associated with increased platelet reactivity. In diabetes patients, augmented MPV was proposed to contribute to increased risk of thrombotic complications. Therefore, the aim of this study was to investigate whether under hyperglycemic conditions, aldose reductase (AR)-mediated sorbitol formation and associated rise in cell volume, which subsequently results in platelet hyperactivation. Platelets were obtained from 30 healthy volunteers and 13 patients with diabetes...
September 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28818855/paradigm-of-biased-par1-protease-activated-receptor-1-activation-and-inhibition-in-endothelial-cells-dissected-by-phosphoproteomics
#3
Bart L van den Eshof, Arie J Hoogendijk, Pelle J Simpson, Floris P J van Alphen, Sara Zanivan, Koen Mertens, Alexander B Meijer, Maartje van den Biggelaar
OBJECTIVE: Thrombin is the key serine protease of the coagulation cascade and mediates cellular responses by activation of PARs (protease-activated receptors). The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events. However, it has remained unclear whether thrombin signaling is exclusively mediated through PAR1. Furthermore, mechanistic insight into activation and inhibition of PAR1-mediated EC signaling is lacking...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28817667/glycoprotein-ib-activation-by-thrombin-stimulates-the-energy-metabolism-in-human-platelets
#4
Norma Corona de la Peña, Manuel Gutiérrez-Aguilar, Ileana Hernández-Reséndiz, Álvaro Marín-Hernández, Sara Rodríguez-Enríquez
Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway i.e., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3-38 times vs...
2017: PloS One
https://www.readbyqxmd.com/read/28805478/production-of-platelet-rich-plasma-gel-from-elderly-patients-under-antithrombotic-drugs-perspectives-in-chronic-wounds-care
#5
M Velier, J Magalon, A Daumas, M Cassar, P Francois, A Ghazouane, C Philandrianos, B Bertrand, C Frere, D Bernot, P Villani, F Dignat George, F Sabatier
Platelet-Rich Plasma (PRP) is an autologous biological therapy obtained by centrifuging the patient's own blood to concentrate platelets. The addition of autologous thrombin and calcium chloride to PRP allows the production of a semi-solid form called PRP gel. PRP gel is increasingly used in a variety of tissue defects and predominantly in the management of non-healing chronic wounds. The topical application of PRP gel seems promising due to the capability of platelets to store and secrete growth factors (GF), fibrin and cytokines, which are essentials for wound healing...
August 14, 2017: Platelets
https://www.readbyqxmd.com/read/28805299/dissociation-between-the-pharmacokinetics-and-pharmacodynamics-of-once-daily-rivaroxaban-and-twice-daily-apixaban-a-randomized-crossover-study
#6
Reinhold Kreutz, Pontus B Persson, Dagmar Kubitza, Kirstin Thelen, Stefan Heitmeier, Stephan Schwers, Michael Becka, Melanie Hemmrich
BACKGROUND: The anticoagulant actions of the oral direct factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. OBJECTIVES: To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in nonvalvular atrial fibrillation. METHODS: Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32)...
August 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28804852/the-overall-hemostatic-potential-ohp-assay
#7
Jennifer Curnow
The principle of the overall hemostatic potential (OHP) assay is the generation of a fibrin time curve by optical density readings, which represent the balance between fibrin generation, triggered by thrombin or tissue factor, and fibrinolysis, triggered by tissue plasminogen activator (tPA). OHP measures the integrated effect of procoagulant, anticoagulant, and fibrinolytic factors, and OHP assay parameters provide a means of quantifying both the coagulation and fibrinolytic potential of platelet poor plasma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804851/thrombin-generation-assays-tgas
#8
Gian Luca Salvagno, Erik Berntorp
In recent years, there has been a revival of interest in a time-honored tool of the clotting trade: the thrombin generation curve or thrombin generation (TG) assay (TGA) as we now call it. Thrombin generation is a key coagulation process that determines the extent of a hemostatic plug or a thrombotic process. The recent development of newer tests based on the continuous registration of TG under in vitro conditions that mimic more closely what occurs in vivo prompted us to reinvestigate the balance between procoagulants and anticoagulants in patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804827/assessment-of-hereditary-thrombophilia-performance-of-antithrombin-at-testing
#9
Jana N Gausman, Richard A Marlar
Antithrombin (AT) is a naturally occurring plasma inhibitor of coagulation, which is a synthesized in the liver. AT inhibits coagulation serine proteases (the enzymatically activated forms of the clotting factors), mainly thrombin (factor IIa) and factor Xa, but also to a lesser extent factors IXa, XIa, and XIIa. Acting alone, AT inhibits coagulation factors, but does this very slowly; however, when coupled with heparin as a cofactor, the speed of inhibition is increased many fold. The AT/Heparin complex is the most powerful naturally occurring anticoagulant in blood...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804824/laboratory-testing-for-activated-protein-c-resistance-apcr
#10
Soma Mohammed, Emmanuel J Favaloro
Activated protein C resistance (APCR) describes a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. Protein C is a natural anticoagulant that is synthesized in the liver and is activated to APC via proteolysis. APC then degrades Factors Va and VIIIa. APCR describes the reduced inability of APC to cleave Factors Va and VIIIa, which therefore promotes increased thrombin generation and potentially leads to a prothrombotic state...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28802974/characteristics-of-thrombin-generation-in-a-fulminant-porcine-sepsis-model
#11
Judit Tóth, Ildikó Beke Debreceni, Ádám Deák, Katalin Pető, Mariann Berhés, Endre Hajdú, Judit Szabó, Norbert Németh, Béla Fülesdi, János Kappelmayer
INTRODUCTION: The activation of blood coagulation has been demonstrated in most cases of sepsis, however previous studies in humans could not detect hypercoagulability with global hemostasis assays. In a fulminant porcine sepsis model we analysed coagulation screening tests and thrombin generation to evaluate hemostatic alterations. MATERIALS AND METHODS: Live Escherichia coli bacteria were inoculated to female pigs and prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen were measured by coagulometry...
August 1, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28802535/the-effects-of-autologous-platelet-rich-fibrin-on-flexor-tendon-healing-in-a-rabbit-model
#12
Janice C Y Liao, Min He, Aaron W T Gan, Alphonsus K S Chong
PURPOSE: Platelet-rich plasma containing large amounts of growth factors is purported to increase repaired flexor tendon strength. However, the use of bovine thrombin has the risk of antibody formation. We evaluated the effects of the newer generation autologous platelet-rich fibrin (PRF) on flexor tendon healing. METHODS: We performed surgical repair of 32 flexor tendons from the index and ring digits of the hind paws of 8 New Zealand white rabbits. In the PRF group, the PRF membrane was either wrapped around or interposed between the repair sites...
August 9, 2017: Journal of Hand Surgery
https://www.readbyqxmd.com/read/28799234/arhgef10-knockout-inhibits-platelet-aggregation-and-protects-mice-from-thrombus-formation
#13
Dai-Hua Lu, Chun-Chieh Hsu, Shiu-Wen Huang, Huang-Ju Tu, Tur-Fu Huang, Houng-Chi Liou, Hsiao-Mei Liao, Chia-Hsiang Chen, Wen-Mei Fu, Susan Shur-Fen Gau
BACKGROUND: ARHGEF10, a member of Rho guanine nucleotide exchange factors (GEF) family, stimulates the Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors such as cell polarity, cytoskeletal organization and gene transcription. ARHGEF10 SNPs are linked with the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown. OBJECTIVE: To examine the role of ARHGEF10 in platelet function. METHODS: ARHGEF10 knockout mice were generated...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28775073/clots-are-potent-triggers-of-inflammatory-cell-gene-expression-indications-for-timely-fibrinolysis
#14
Robert A Campbell, Adriana Vieira-de-Abreu, Jesse W Rowley, Zechariah G Franks, Bhanu Kanth Manne, Matthew T Rondina, Larry W Kraiss, Jennifer J Majersik, Guy A Zimmerman, Andrew S Weyrich
OBJECTIVE: Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. Determine whether clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases. APPROACH AND RESULTS: We performed next-generation RNA sequencing on monocytes extracted from whole blood clots and using a purified plasma clot system...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28771917/5b9-a-monoclonal-anti-platelet-factor-4-heparin-igg-with-a-human-fc-fragment-that-mimics-heparin-induced-thrombocytopenia-antibodies
#15
C Kizlik-Masson, C Vayne, S E McKenzie, A Poupon, Y Zhou, G Champier, Pouplard C, Y Gruel, J Rollin
BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is based on clinical and biological criteria, but a standard is lacking for laboratory assays. Moreover, no humanized HIT antibody is available for pathophysiological studies. OBJECTIVE: To characterise 5B9, a chimeric monoclonal antibody, which fully mimics the effects of human HIT antibodies. METHODS/RESULTS: 5B9, a chimeric anti-PF4/H IgG1 antibody was obtained after immunizing specific transgenic mice...
August 3, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28771279/superoxide-dismutase-2-is-dispensable-for-platelet-function
#16
Trevor P Fidler, Jesse W Rowley, Claudia Araujo, Luc H Boudreau, Alex Marti, Rhonda Souvenir, Kali Dale, Eric Boilard, Andrew S Weyrich, E Dale Abel
Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation...
August 3, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28750471/modulation-of-the-activated-protein-c-pathway-in-severe-haemophilia-a-patients-the-effects-of-thrombomodulin-and-a%C3%A2-factor-v-stabilizing-fab
#17
D F Brophy, E J Martin, B M Mohammed, J C Barrett, J G Kuhn, M E Nolte, B Wiinberg, H L Holmberg, J Lund, R Salbo, E K Waters
INTRODUCTION: The thrombomodulin (TM)/activated protein C (APC) system is a key regulator of haemostasis, limiting amplification and propagation of the formed blood clot to the injury site. Dampening APC's inhibition of factor V (FV) and factor VIII (FVIII) may be a future strategy in developing next-generation therapeutic targets for haemophilia treatment. AIMS: To determine ex vivo the respective concentration-dependent effects of TM and a FV-stabilizing Fab on the APC regulatory pathway in severe FVIII-deficient blood and plasma...
July 27, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28748351/pig-tissue-factor-pathway-inhibitor-%C3%AE-fusion-immunoglobulin-inhibits-pig-tissue-factor-activity-in-human-plasma-moderately-more-efficiently-than-the-human-counterpart
#18
Chang-Yong Choi, Yeon-Hui Kim, Joonbeom Bae, Suk Jun Lee, Hyun Kyung Kim, Chung-Gyu Park, Taehoon Chun
OBJECTIVE: To determine the efficacy of soluble pig tissue factor pathway inhibitor fusion immunoglobulin (TFPI-Ig) in blocking pig to human xenogeneic blood coagulation. RESULTS: To generate pig TFPI-Ig or human TFPI-Ig, expression vector containing cDNA encoding pig TFPIα or human TFPIα combined with human constant Ig heavy chain region was cloned and introduced into CHO cells. After purification of pig TFPI-Ig and human TFPI-Ig, the inhibition of each recombinant protein on pig tissue factor (TF)-mediated blood coagulation was examined in human plasma...
July 26, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28747771/different-potential-of-extracellular-vesicles-to-support-thrombin-generation-contributions-of-phosphatidylserine-tissue-factor-and-cellular-origin
#19
Carla Tripisciano, René Weiss, Tanja Eichhorn, Andreas Spittler, Thomas Heuser, Michael Bernhard Fischer, Viktoria Weber
Cells release diverse types of vesicles constitutively or in response to proliferation, injury, inflammation, or stress. Extracellular vesicles (EVs) are crucial in intercellular communication, and there is emerging evidence for their roles in inflammation, cancer, and thrombosis. We investigated the thrombogenicity of platelet-derived EVs, which constitute the majority of circulating EVs in human blood, and assessed the contributions of phosphatidylserine and tissue factor exposure on thrombin generation. Addition of platelet EVs to vesicle-free human plasma induced thrombin generation in a dose-dependent manner, which was efficiently inhibited by annexin V, but not by anti-tissue factor antibodies, indicating that it was primarily due to the exposure of phosphatidylserine on platelet EVs...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745733/neutrophil-extracellular-trap-formation-upon-exposure-of-hydrophobic-materials-to-human-whole-blood-causes-thrombogenic-reactions
#20
Claudia Sperling, Marion Fischer, Manfred F Maitz, Carsten Werner
Neutrophil extracellular trap (NET) formation, a reaction of the innate immune system to fight pathogens, was shown to be involved in thrombus formation. In the present study blood-contacting biomaterials with graded surface characteristics were investigated as a potential cause of NET formation on medical devices. Surface properties are known to govern protein adsorption, cell adhesion and ultimately the activation of several other host defense pathways - potentially also the formation of NETs. Model materials of defined hydrophilic or hydrophobic properties (glass, and thin films of poly(ethylene-alt-maleic anhydride), self-assembled monolayers of methyl terminated alkanethiols, and Teflon AF™) were incubated either with isolated human granulocytes after pre-adsorption with plasma proteins or with human whole blood...
July 26, 2017: Biomaterials Science
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