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https://www.readbyqxmd.com/read/29452445/suppressive-role-of-tissue-factor-pathway-inhibitor-%C3%AE-in-platelet-dependent-fibrin-formation-under-flow-is-restricted-to-low-procoagulant-strength
#1
Stella Thomassen, Tom G Mastenbroek, Frauke Swieringa, Kristien Winckers, Marion A H Feijge, Roy Schrijver, Judith M E M Cosemans, Susan A Maroney, Alan E Mast, Tilman M Hackeng, Johan W M Heemskerk
Tissue factor pathway inhibitor-alpha (TFPI-α) is a Kunitz-type serine protease inhibitor, which suppresses coagulation by inhibiting the tissue factor (TF)/factor VIIa complex as well as factor Xa. In static plasma-phospholipid systems, TFPI-α thus suppresses both factor Xa and thrombin generation. In this article, we used a microfluidics approach to investigate how TFPI-α regulates fibrin clot formation in platelet thrombi at low wall shear rate. We therefore hypothesized that the anticoagulant effect of TFPI-α in plasma is a function of the local procoagulant strength-defined as the magnitude of thrombin generation under flow, due to local activities of TF/factor VIIa and factor Xa...
February 16, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29439639/thrombin-generation-biomarkers-decline-with-parenteral-anticoagulation-an-overlooked-means-of-anticoagulation-monitoring
#2
Craig P McFarland, Stuart E Lind
Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been available for more than 2 decades, they are not routinely used in clinical trials or practice to monitor anticoagulation therapy. We observed a fall in one such marker, the D-dimer antigen, in patients receiving anticoagulation therapy. We therefore conducted a systematic review of the medical literature to document the change in serum biomarkers of thrombin generation following the initiation of anticoagulation therapy...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29437578/tissue-factor-an-essential-mediator-of-hemostasis-and-trigger-of-thrombosis
#3
REVIEW
Steven P Grover, Nigel Mackman
Tissue factor (TF) is the high-affinity receptor and cofactor for FVII/VIIa. The TF-FVIIa complex is the primary initiator of blood coagulation and plays an essential role in hemostasis. TF is expressed on perivascular and epithelial cells at organ and body surfaces where it forms a hemostatic barrier. TF also provides additional hemostatic protection to vital organs, such as the brain, lung, and heart. Under pathological conditions, TF can trigger both arterial and venous thrombosis. For instance, atherosclerosis plaques contain high levels of TF on macrophage foam cells and microvesicles that drives thrombus formation after plaque rupture...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29427885/a-nonenzymatic-dna-nanomachine-for-biomolecular-detection-by-target-recycling-of-hairpin-dna-cascade-amplification
#4
Jiao Zheng, Ningxing Li, Chunrong Li, Xinxin Wang, Yucheng Liu, Guobin Mao, Xinghu Ji, Zhike He
Synthetic enzyme-free DNA nanomachine performs quasi-mechanical movements in response to external intervention, suggesting the promise of constructing sensitive and specific biosensors. Herein, a smart DNA nanomachine biosensor for biomolecule (such as nucleic acid, thrombin and adenosine) detection is developed by target-assisted enzyme-free hairpin DNA cascade amplifier. The whole DNA nanomachine system is constructed on gold nanoparticle which decorated with hundreds of locked hairpin substrate strands serving as DNA tracks, and the DNA nanomachine could be activated by target molecule toehold-mediated exchange on gold nanoparticle surface, resulted in the fluorescence recovery of fluorophore...
January 31, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29427073/dissecting-the-biochemical-architecture-and-morphological-release-pathways-of-the-human-platelet-extracellular-vesiculome
#5
Silvia H De Paoli, Tseday Z Tegegn, Oumsalama K Elhelu, Michael B Strader, Mehulkumar Patel, Lukas L Diduch, Ivan D Tarandovskiy, Yong Wu, Jiwen Zheng, Mikhail V Ovanesov, Abdu Alayash, Jan Simak
Platelet extracellular vesicles (PEVs) have emerged as potential mediators in intercellular communication. PEVs exhibit several activities with pathophysiological importance and may serve as diagnostic biomarkers. Here, imaging and analytical techniques were employed to unveil morphological pathways of the release, structure, composition, and surface properties of PEVs derived from human platelets (PLTs) activated with the thrombin receptor activating peptide (TRAP). Based on extensive electron microscopy analysis, we propose four morphological pathways for PEVs release from TRAP-activated PLTs: (1) plasma membrane budding, (2) extrusion of multivesicular α-granules and cytoplasmic vacuoles, (3) plasma membrane blistering and (4) "pearling" of PLT pseudopodia...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29412936/label-free-electrochemical-biosensors-based-on-3-3-5-5-tetramethylbenzidine-responsive-isoporous-silica-micelle-membrane
#6
Qinqin Sun, Fei Yan, Bin Su
3,3',5,5'-Tetramethylbenzidine (TMB) has been frequently used as an indicator in G-quadruplex/hemin DNAzyme (G4zyme)-based chemical and biochemical analysis, and its oxidation products are usually monitored by electrochemical or optical methods to quantify G4zyme formation-related analytes. Herein we report a simple electrochemical approach based on isoporous silica-micelle membrane (iSMM) to measure TMB, instead of its oxidation products, in G4zyme-based detection of specific analytes. The iSMM was grown on the indium tin oxide (ITO) electrode, which was composed of highly ordered, vertically oriented silica nanochannels and cylindrical micelles of cetyltrimethylammonium...
May 15, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29407633/the-lectin-pathway-and-coagulation-in-lung-cancer-patients-undergoing-lobectomy-a-randomised-controlled-trial
#7
Julie Brogaard Larsen, Anne Troldborg, Thomas Decker Christensen, Christine Lodberg Hvas, Steffen Thiel, Anne-Mette Hvas
BACKGROUND: Lectin pathway proteases activate coagulation and may theoretically play a role in the increased thrombosis risk in cancer, which is especially high during surgery. AIMS: To investigate lectin pathway proteins during lung cancer surgery, the influence of low molecular weight heparin (LMWH) on lectin pathway proteins, and correlations between lectin pathway proteins and coagulation. METHODS: Fifty lung cancer patients undergoing video-assisted thoracoscopic surgery lobectomy were randomised to LMWH, n = 26, or no anticoagulant (control), n = 24...
January 30, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29407626/laboratory-biomarkers-for-venous-thromboembolism-risk-in-patients-with-hematologic-malignancies-a-review
#8
REVIEW
B T Samuelson Bannow, B A Konkle
INTRODUCTION: Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk. MATERIALS AND METHODS: We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database...
January 31, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29406387/in-silico-thrombin-and-factor-xa-generation-profiles-in-adult-patients-after-fontan-operation
#9
Matthew Gissel, Lidia Tomkiewicz-Pajak, Piotr Podolec, Piotr Hoffman, Olga Trojnarska, Magdalena Lipczyńska, Anetta Undas, Kathleen E Brummel-Ziedins
: Single-ventricle defects are associated with increased risk of thromboembolic events. To analyze the prothrombotic potential in a long-term follow-up on Fontan patients via plasma contribution to thrombin and factor (F)Xa generation profiles. Thrombin and FXa generation was simulated from plasma concentrations of FII, FV, FVII, FVIII, FIX, FX, antithrombin and tissue factor (TF) pathway inhibitor from Fontan patients (n = 48) and healthy controls (n = 34). TF and thrombin-antithrombin complex (TAT) were measured by ELISA...
February 5, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29402840/elevations-of-thrombotic-biomarkers-in-hemoglobin-h-disease
#10
Siriyakorn Chansai, Supan Fucharoen, Goonnapa Fucharoen, Arunee Jetsrisuparb, Worawan Chumpia
BACKGROUND: Thalassemia is a group of hereditary hemoglobinopathies caused by decreased or absent synthesis of α and/or β globin chains. Studies have shown that hypercoagulability and thrombosis are common clinical symptoms in β-thalassemia, especially β-thalassemia intermedia, but little is known about in α-thalassemia. This study aims to examine phosphatidylserine (PS) levels, platelet activation, and coagulation markers in splenectomized (S) and nonsplenectomy (NS) patients with hemoglobin (Hb) H disease...
January 18, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29402705/treatment-tailoring-for-factor-v-deficient-patients-and-perioperative-management-using-global-hemostatic-coagulation-assays
#11
Sarina Levy-Mendelovich, Assaf Arie Barg, Nurit Rosenberg, Einat Avishai, Jacob Luboshitz, Mudi Misgav, Gili Kenet, Tami Livnat
INTRODUCTION: Congenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. AIM: To optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM)...
February 2, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29399204/thrombi-produced-in-stagnation-point-flows-have-a-core-shell-structure
#12
Bradley A Herbig, Scott L Diamond
Introduction: In regions of flow separation/reattachment within diseased arteries, the local hemodynamics can result in stagnation point flow that provides an atypical environment in atherosclerosis. Impinging flows occur with recirculation eddies distal of coronary stenosis or diseased carotid bifurcations. Methods: By perfusing whole blood directly perpendicular to a fibrillar collagen thrombotic surface, a microfluidic device produced a stagnation point flow...
December 2017: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/29389738/the-effects-of-angiotensin-converting-enzyme-inhibition-and-alpha-1-adrenergic-receptor-blockade-on-inflammation-and-hemostasis-in-human-hypertension
#13
M Ekholm, A Jekell, N H Wallén, B Gigante, T Kahan
Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks...
January 30, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29378359/dimeric-glycoprotein-vi-binds-to-collagen-but-not-to-fibrin
#14
Mariam Ebrahim, Janina Jamasbi, Kristin Adler, Remco T A Megens, Yacine M'Bengue, Xavier Blanchet, Kerstin Uhland, Martin Ungerer, Richard Brandl, Christian Weber, Natalie Elia, Reinhard Lorenz, Götz Münch, Wolfgang Siess
Platelet glycoprotein VI (GPVI) acts as a decisive collagen receptor in atherothrombosis. Besides collagen, injured atherosclerotic plaques expose tissue factor (TF) that triggers fibrin formation. Two recent studies reported that platelet GPVI also functions as fibrin receptor, which would importantly widen the mode of action of GPVI-targeted antithrombotic drugs. We studied the binding of two GPVI fusion proteins to fibrin under static and arterial flow conditions. Fibrin was prepared from purified fibrinogen or generated more physiologically from endogenous fibrinogen by coagulating plasma with thrombin...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29378358/chemical-footprinting-reveals-conformational-changes-following-activation-of-factor-xi
#15
Ingrid Stroo, J Arnoud Marquart, Kamran Bakhtiari, Tom Plug, Alexander B Meijer, Joost C M Meijers
Coagulation factor XI is activated by thrombin or factor XIIa resulting in a conformational change that converts the catalytic domain into its active form and exposing exosites for factor IX on the apple domains. Although crystal structures of the zymogen factor XI and the catalytic domain of the protease are available, the structure of the apple domains and hence the interactions with the catalytic domain in factor XIa are unknown. We now used chemical footprinting to identify lysine residue containing regions that undergo a conformational change following activation of factor XI...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29378352/atherothrombosis-and-thromboembolism-position-paper-from-the-second-maastricht-consensus-conference-on-thrombosis
#16
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29365322/rivaroxaban-dose-adjustment-using-thrombin-generation-in-severe-congenital-protein-c-deficiency-and-warfarin-induced-skin-necrosis
#17
Neethu Menon, Ravi Sarode, Ayesha Zia
No abstract text is available yet for this article.
January 23, 2018: Blood Advances
https://www.readbyqxmd.com/read/29365311/biocompatible-coupling-of-therapeutic-fusion-proteins-to-human-erythrocytes
#18
Carlos H Villa, Daniel C Pan, Ian H Johnston, Colin F Greineder, Landis R Walsh, Elizabeth D Hood, Douglas B Cines, Mortimer Poncz, Don L Siegel, Vladimir R Muzykantov
Carriage of drugs by red blood cells (RBCs) modulates pharmacokinetics, pharmacodynamics, and immunogenicity. However, optimal targets for attaching therapeutics to human RBCs and adverse effects have not been studied. We engineered nonhuman-primate single-chain antibody fragments (scFvs) directed to human RBCs and fused scFvs with human thrombomodulin (hTM) as a representative biotherapeutic cargo (hTM-scFv). Binding fusions to RBCs on band 3/glycophorin A (GPA; Wright b [Wrb] epitope) and RhCE (Rh17/Hr0 epitope) similarly endowed RBCs with hTM activity, but differed in their effects on RBC physiology...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29364133/hierarchy-and-assortativity-as-new-tools-for-binding-affinity-investigation-the-case-of-the-tba-aptamer-ligand-complex
#19
Rosella Cataldo, Eleonora Alfinito, Lino Reggiani
Aptamers are single stranded DNA, RNA, or peptide sequences having the ability to bind several specific targets (proteins, molecules as well as ions). Therefore, aptamer production and selection for therapeutic and diagnostic applications is very challenging. Usually, they are generated in vitro, although computational approaches have been recently developed for the in silico production. Despite these efforts, the mechanism of aptamer-ligand formation is not completely clear, and producing high-affinity aptamers is still quite difficult...
December 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/29362190/which-antiplatelet-therapy-in-patients-with-left-ventricular-assist-device-and-aspirin-allergy
#20
Filippo Consolo, Loris Pozzi, Giulia Sferrazza, Patrizia Della Valle, Armando D'Angelo, Marvin J Slepian, Federico Pappalardo
In patients with left ventricular assist device support and aspirin allergy, the choice of effective antiplatelet strategy remains a challenge. We compared the antithrombotic effect of clopidogrel vs ticagrelor in an LVAD patient with aspirin allergy by using a modified protocol of the thrombin generation test, accounting selectively for the platelet contribution on thrombin generation. Our results demonstrate enhanced antithrombotic efficacy offered by ticagrelor. Consistent with experimental results, the patient has passed more than 300 days without thromboembolic complications...
February 2018: Annals of Thoracic Surgery
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