DOCSLIB.ORG

63Rd Annual SSC Meeting, in Conjunction with the 2017 ISTH Congress in Berlin, Germany Meeting Minutes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
63Rd Annual SSC Meeting, in Conjunction with the 2017 ISTH Congress in Berlin, Germany Meeting Minutes 63rd Annual SSC meeting, in conjunction with the 2017 ISTH Congress in Berlin, Germany Meeting Minutes Standing Committees Coagulation Standards Committee ............................................................... 3 Subcommittees Animal, Cellular and Molecular Models ........................................................ 5 Biorheology .................................................................................................. 7 Control of Anticoagulation ............................................................................ 10 Disseminated Intravascular Coagulation ...................................................... 12 Factor VIII, Factor IX and Rare Coagulation Disorders ................................ 14 Factor XI and the Contact System ................................................................ 19 Factor XIII and Fibrinogen ............................................................................ 21 Fibrinolysis ................................................................................................... 27 Genomics in Thrombosis and Hemostasis ................................................... 33 Hemostasis and Malignancy......................................................................... 46 Lupus Anticoagulant/Phospholipid Dependent Antibodies ........................... 49 Pediatric and Neonatal Hemostasis and Thrombosis ................................... 54 Perioperative Thrombosis and Hemostasis .................................................. 59 Plasma Coagulation Inhibitors ...................................................................... 61 Platelet Immunology ..................................................................................... 66 Platelet Physiology ....................................................................................... 73 Predictive and Diagnostic Variables in Thrombotic Disease......................... 77 Vascular Biology ........................................................................................... 79 Von Willebrand Factor .................................................................................. 83 Women’s Health Issues in Thrombosis and Hemostasis .............................. 91 Coagulation Standards Standing Committee Minutes 9 July 2017 12:30 - 13:30 Chairman: Anthony R. Hubbard Review of ISTH/SSC Secondary Coagulation Standard Lot #4 (A Hubbard) Dispatch of Lot #4: Between the beginning of June 2016 and the end of May 2017 there were a total of 58 orders from 23 different manufacturers and 2 external quality assurance schemes (College of American Pathologists & UK NEQAS); a total of 13,872 vials were issued. Lot #4 was also included in multi-centre studies for the value assignment of Lot #5. Remaining stock at the end of May 2017 was 31,700 vials. Based on the dispatch of Lot #4 since 2012 it is predicted that stocks will be exhausted around 2019 – 2020. Stability of Lot #4: Stability monitoring by accelerated degradation is now complete for Lot #4 and the predicted degradation rates for the four test analytes (factor V, factor VII, factor VIII, Antithrombin) are all less than 0.1% loss per year at -20°C. This is consistent with previous lots of the standard and confirms that Lot #4 is extremely stable. Real-time stability testing will be carried out in 2018 to compare vials stored at the bulk storage temperature (-20°C) with vials stored at -70°C for the 4 analytes in order to have an objective measure of stability of -20°C. Troubleshooting: It was reported that the use of the standard for troubleshooting purposes, by EQA schemes, has been renewed for a further 4 years from November 2016. Calibration for VWF:GPIbR & VWF:GPIbM methods: Following the VWF sub- committee proposal to adopt the VWF:RCo value on the WHO 6th IS FVIII/VWF Plasma for these new methods it was announced that the calibration of Lots #4 and #5 for VWF:GPIbR & VWF:GPIbM will be carried out by assay against the WHO 6th IS in Q4 2017. Experience of EQA schemes with Lot #4 UK NEQAS (S Kitchen) The use of Lot #4 for troubleshooting was reviewed. Between 2008 and 2016 there were 49 vials issued for this purpose (covering factors II, V, VIII, IX, XI, VWF, fibrinogen, Antithrombin, Protein C, Protein S). In the last 12 months vials were issued for troubleshooting problems in factor VIII, Protein C, fibrinogen and VWF. There was an update on a survey result for factor II, previously reported in 2016, where results were 15% higher with one commercial reference plasma. Tests indicated this was not related to the use of different thromboplastin reagents but to the reference plasma used. A survey in April 2017 showed this issue was still unresolved. Correspondence with the manufacturer indicated they were addressing the calibration of their product and that the last batches affected by this issue were dispatched in January 2016. A survey of VWF testing in May 2017 returned median results for VWF:Ag, VWF:CB and VWF:RCo in excellent agreement with the labelled values for Lot #4; results for VWF:Ab and VWF:GPIbR were higher than VWF:RCo whereas the median for VWF:GPIbM was close to the VWF:RCo value. These results were very similar to a survey carried out in 2012. College of American Pathologists (R A Higgins) Lot #4 was issued in two surveys in 2016; one for thrombophilia testing and a special survey for VWF. Analytes are tested at the discretion of participating laboratories. Results are presented as mean and median for 10 or more participants and only as median for less than 10 participants. Results for Antithrombin activity were close to the assigned value for Lot #4 whereas the median from one antigen method was around 10% higher. Mean estimates for Protein C activity by chromogenic methods were close to the assigned value whereas one clotting end-point method gave much higher results (116 vs 92 IU/dl). Results for Protein S activity and free Protein S antigen were generally close to the assigned value whereas one estimate for total Protein S antigen differed by around 10%. Results for factor VIII activity agreed closely to the assigned for one method (21 labs) but differed by around 10% with another high use method (15 labs). A study of trends for factor VIII indicated an approx. 10% increase in survey results by 3 different methods during 2015; the reason for this increase in unclear and is not linked to any change in Lot #4 or the WHO IS. VWF activity (VWF:RCo) results were close to the assigned for the most popular method; results for the VWF:GPIbR method were slightly higher than the VWF:RCo value. Review of the trends for VWF:RCo estimates indicated that the very large variability between methods seen in 2014 has been reduced in more recent surveys. VWF:Ag results from 3 different methods were in good agreement with the assigned value. Towards Lot #5 (C Thelwell) The project to develop Lot #5 was initiated following approval by the ISTH Council in November 2015. Procurement of Lot #5 was completed in 2016 after the review of bids from two manufacturers. Lot #5 consists of a batch of 100,000 vials and was delivered to NIBSC on 31 January 2017 where it is now stored at -20°C. Some vials were placed at elevated temperatures on 09 March 2017 for the accelerated degradation studies. The value assignment will be carried out in 3 separate exercises during 2017. The first exercise will cover Protein C, Protein S, Antithrombin and Fibrinogen; the second will cover factors, II, VII, IX, X, XI and XIII; the third exercise will cover factor VIII and VWF. Value assignment for factor V will be carried out as part of the project to replace the WHO IS. The whole calibration exercise will include 77 laboratories recruited from 30 countries. Four independent estimates will be requested for each analyte from each testing laboratory and the assigned values will be calculated as the geometric means of results returned by the participants. The objective is to complete this value assignment in time for endorsement at the SSC meeting in Dublin 2018. It is intended to also value assign Lot #5 for FXII following establishment of the new WHO IS Factor XIII plasma in October 2017; this will be undertaken in a separate study. There were 22 attendees. Animal, Cellular and Molecular Models 9 July 2017 8:00 – 12:15 Chairman: Jose A. Diaz Co-Chairs: Brian Cooley, Alexandra Kopic, Nobuo Nagal, Lesile Parise, Denise E Sabatino 8-10am: AAA MODEL–Elastase Model AAA Peri-Adventitial Model AAA Angiotensin II Model Cremaster Arteriole Laser-Injury Model of Thrombosis Summary: Drs. English, Grover and Daugherty covered advantages, disadvantages, limitations and applications of each model. All speakers engaged the audience and this was translated into many questions following the talks (all talks had at least 3 questions) Break 15 minutes 10:15 – 11:15 Educational session: Murine IVC thrombosis model: Tips and Tricks IVC Stenosis Model: Latest modifications Summary: Drs. Diaz and Saha delivered two educational talks. Diaz highlighted tips and tricks for VT models, how to approach the abdominal cavity, anatomical signature and landmarks, as well as postoperative care of the animals. Saha presented an overview of the stenosis model (one of the most widely used animal models) and delivered, as he was asked, all the modifications introduced during the last 7 years that had caused some confusion in the field. 11:15 – 12:15 Lectures: Directing Your Research: Unmet Needs from the Clinical Perspective Dr. Saha (last minute replacement for Dr. Lurie) presented gaps in the field
Load more

Recommended publications
  • Hemoglobin Interaction with Gp1ba Induces Platelet Activation And
    ARTICLE Platelet Biology & its Disorders Hemoglobin interaction with GP1bα induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis Rashi Singhal,1,2,* Gowtham K. Annarapu,1,2,* Ankita Pandey,1 Sheetal Chawla,1 Amrita Ojha,1 Avinash Gupta,1 Miguel A. Cruz,3 Tulika Seth4 and Prasenjit Guchhait1 1Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region, Biotech Science Cluster, Faridabad, India; 2Biotechnology Department, Manipal University, Manipal, Karnataka, India; 3Thrombosis Research Division, Baylor College of Medicine, Houston, TX, USA, and 4Hematology, All India Institute of Medical Sciences, New Delhi, India *RS and GKA contributed equally to this work. ABSTRACT Intravascular hemolysis increases the risk of hypercoagulation and thrombosis in hemolytic disorders. Our study shows a novel mechanism by which extracellular hemoglobin directly affects platelet activation. The binding of Hb to glycoprotein1bα activates platelets. Lower concentrations of Hb (0.37-3 mM) significantly increase the phos- phorylation of signaling adapter proteins, such as Lyn, PI3K, AKT, and ERK, and promote platelet aggregation in vitro. Higher concentrations of Hb (3-6 mM) activate the pro-apoptotic proteins Bak, Bax, cytochrome c, caspase-9 and caspase-3, and increase platelet clot formation. Increased plasma Hb activates platelets and promotes their apoptosis, and plays a crucial role in the pathogenesis of aggregation and development of the procoagulant state in hemolytic disorders. Furthermore, we show that in patients with paroxysmal nocturnal hemoglobinuria, a chronic hemolytic disease characterized by recurrent events of intravascular thrombosis and thromboembolism, it is the elevated plasma Hb or platelet surface bound Hb that positively correlates with platelet activation.
    [Show full text]
  • Common Gene Polymorphisms Associated with Thrombophilia
    Chapter 5 Common Gene Polymorphisms Associated with Thrombophilia Christos Yapijakis, Zoe Serefoglou and Constantinos Voumvourakis Additional information is available at the end of the chapter http://dx.doi.org/10.5772/61859 Abstract Genetic association studies have revealed a correlation between DNA variations in genes encoding factors of the hemostatic system and thrombosis-related disease. Certain var‐ iant alleles of these genes that affect either gene expression or function of encoded protein are known to be genetic risk factors for thrombophilia. The chapter presents the current genetics and molecular biology knowledge of the most important DNA polymorphisms in thrombosis-related genes encoding coagulation factor V (FV), coagulation factor II (FII), coagulation factor XII (FXII), coagulation factor XIII A1 subunit (FXIIIA1), 5,10- methylene tetrahydrofolate reductase (MTHFR), serpine1 (SERPINE1), angiotensin I-con‐ verting enzyme (ACE), angiotensinogen (AGT), integrin A2 (ITGA2), plasma carboxypeptidase B2 (CPB2), platelet glycoprotein Ib α polypeptide (GP1BA), thrombo‐ modulin (THBD) and protein Z (PROZ). The molecular detection methods of each DNA polymorphism is presented, in addition to the current knowledge regarding its influence on thrombophilia and related thrombotic events, including stroke, myocardial infarction, deep vein thrombosis, spontaneous abortion, etc. In addition, best thrombosis prevention strategies with a combination of genetic counseling and molecular testing are discussed. Keywords: Thrombophilia, coagulation
    [Show full text]
  • Therapeutic Antibody-Like Immunoconjugates Against Tissue Factor with the Potential to Treat Angiogenesis-Dependent As Well As Macrophage-Associated Human Diseases
    antibodies Review Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases Zhiwei Hu ID Department of Surgery Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, OH 43210, USA; [email protected]; Tel.: +1-614-685-4606 Received: 10 October 2017; Accepted: 18 January 2018; Published: 23 January 2018 Abstract: Accumulating evidence suggests that tissue factor (TF) is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD), endometriosis and rheumatoid arthritis (RA). Macrophage is involved in the progression of a variety of human diseases, such as atherosclerosis and viral infections (human immunodeficiency virus, HIV and Ebola). It is well documented that TF is selectively expressed on angiogenic vascular endothelial cells (VECs) in these pathological angiogenesis-dependent human diseases and on disease-associated macrophages. Under physiology condition, TF is not expressed by quiescent VECs and monocytes but is solely restricted on some cells (such as pericytes) that are located outside of blood circulation and the inner layer of blood vessel walls. Here, we summarize TF expression on angiogenic VECs, macrophages and other diseased cell types in these human diseases. In cancer, for example, the cancer cells also overexpress TF in solid cancers and leukemia. Moreover, our group recently reported that TF is also expressed by cancer-initiating stem cells (CSCs) and can serve as a novel oncotarget for eradication of CSCs without drug resistance.
    [Show full text]
  • Alternatively Spliced Tissue Factor Induces Angiogenesis Through Integrin Ligation
    Alternatively spliced tissue factor induces angiogenesis through integrin ligation Y. W. van den Berga, L. G. van den Hengela, H. R. Myersa, O. Ayachia, E. Jordanovab, W. Rufc, C. A. Spekd, P. H. Reitsmaa, V. Y. Bogdanove, and H. H. Versteega,1 aThe Einthoven Laboratory for Experimental Vascular Medicine and bDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands; cDepartment of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; dCenter for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; and eDivision of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267 Edited by Charles T. Esmon, Oklahoma Medical Research Foundation, Oklahoma City, OK, and approved September 25, 2009 (received for review May 15, 2009) The initiator of coagulation, full-length tissue factor (flTF), in complex pancreatic cancer cells transfected to express asTF produce more with factor VIIa, influences angiogenesis through PAR-2. Recently, an blood vessels (20), but it remained mechanistically unclear if and alternatively spliced variant of TF (asTF) was discovered, in which part how angiogenesis is regulated by asTF. One possibility is that asTF of the TF extracellular domain, the transmembrane, and cytoplasmic stimulates cancer cells to produce angiogenic factors, but it is also domains are replaced by a unique C terminus. Subcutaneous tumors plausible that asTF enhances angiogenesis via paracrine stimulation produced by asTF-secreting cells revealed increased angiogenesis, but of endothelial cells. Moreover, the role of VIIa, PAR-2 activation it remained unclear if and how angiogenesis is regulated by asTF.
    [Show full text]
  • Endotoxin Enhances Tissue Factor and Suppresses Thrombomodulin Expression of Human Vascular Endothelium in Vitro Kevin L
    Endotoxin Enhances Tissue Factor and Suppresses Thrombomodulin Expression of Human Vascular Endothelium In Vitro Kevin L. Moore,* Sharon P. Andreoli,* Naomi L. Esmon,1 Charles T. Esmon,l and Nils U. Bang1l Department ofMedicine, Section ofHematology/Oncology,* and Department ofPediatrics, Section ofNephrology,t Indiana University School ofMedicine, Indianapolis, Indiana 46223; Oklahoma Medical Research Foundation,§ Oklahoma City, Oklahoma 73104; and Lilly Laboratory for Clinical Research,1' Indianapolis, Indiana 46202 Abstract to support the assembly of clotting factor complexes on their surfaces (13, 14). Endotoxemia is frequently associated clinically with disseminated Under physiologic conditions the thromboresistant properties intravascular coagulation (DIC); however, the mechanism of en- ofthe endothelium are predominant. In some pathological states, dotoxin action in vivo is unclear. Modulation of tissue factor however, this may not be the case. Gram-negative sepsis is fre- (TF) and thrombomodulin (TM) expression on the endothelial quently associated with varying degrees of disseminated intra- surface may be relevant pathophysiologic mechanisms. Stimu- vascular coagulation (DIC),' which is thought to be triggered by lation of human umbilical vein endothelial cells with endotoxin endotoxemia. The pathophysiology of DIC in gram-negative (1 ,ug/ml) increased surface TF activity from 1.52±0.84 to sepsis is complex and the mechanism(s) by which endotoxemia 11.89±8.12 mU/ml-106 cells at 6 h (n = 11) which returned to promotes intravascular coagulation in vivo is unclear. Recently, baseline by 24 h. Repeated stimulation at 24 h resulted in renewed reports by several investigators provide evidence that the throm- TF expression. Endotoxin (1 ,tg/ml) also caused a decrease in boresistance of the endothelial cell is diminished after exposure TM expression to 55.0±6.4% of control levels at 24 h (n = 10) to endotoxin in the absence of other cell types.
    [Show full text]
  • Tissue Factor Regulation, Signaling and Functions Beyond Coagulation with a Focus on Diabetes
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1626 Tissue Factor regulation, signaling and functions beyond coagulation with a focus on diabetes DESIRÉE EDÉN ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-513-0842-5 UPPSALA urn:nbn:se:uu:diva-399599 2020 Dissertation presented at Uppsala University to be publicly examined in Enghoffsalen, Akademiska sjukhuset, ing. 50, Uppsala, Friday, 21 February 2020 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in Swedish. Faculty examiner: Docent, Universitetslektor Sofia Ramström (Örebro Universitet, Institutionen för medicinska vetenskaper). Abstract Edén, D. 2020. Tissue Factor regulation, signaling and functions beyond coagulation with a focus on diabetes. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1626. 65 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0842-5. Background: Tissue factor (TF) is a 47 kDa transmembrane glycoprotein best known for initiating the coagulation cascade upon binding of its ligand FVIIa. Apart from its physiological role in coagulation, TF and TF/FVIIa signaling has proved to be involved in diseases such as diabetes, cancer and cardiovascular diseases. Biological functions coupled to TF/FVIIa signaling include diet-induced obesity, apoptosis, angiogenesis and migration. Aim: The aim of this thesis was to investigate the role of TF/FVIIa in cells of importance in diabetes, to further investigate the mechanism behind TF/FVIIa anti-apoptotic signaling in cancer cells and lastly to examine the regulation of TF expression in monocytes by micro RNAs (miRNA). Results: In paper I we found that TF/FVIIa signaling augments cytokine-induced beta cell death and impairs glucose stimulated insulin secretion from human pancreatic islets.
    [Show full text]
  • General Considerations of Coagulation Proteins
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 8, No. 2 Copyright © 1978, Institute for Clinical Science General Considerations of Coagulation Proteins DAVID GREEN, M.D., Ph.D.* Atherosclerosis Program, Rehabilitation Institute of Chicago, Section of Hematology, Department of Medicine, and Northwestern University Medical School, Chicago, IL 60611. ABSTRACT The coagulation system is part of the continuum of host response to injury and is thus intimately involved with the kinin, complement and fibrinolytic systems. In fact, as these multiple interrelationships have un­ folded, it has become difficult to define components as belonging to just one system. With this limitation in mind, an attempt has been made to present the biochemistry and physiology of those factors which appear to have a dominant role in the coagulation system. Coagulation proteins in general are single chain glycoprotein molecules. The reactions which lead to their activation are usually dependent on the presence of an appropriate surface, which often is a phospholipid micelle. Large molecular weight cofactors are bound to the surface, frequently by calcium, and act to induce a favorable conformational change in the reacting molecules. These mole­ cules are typically serine proteases which remove small peptides from the clotting factors, converting the single chain species to two chain molecules with active site exposed. The sequence of activation is defined by the enzymes and substrates involved and eventuates in fibrin formation. Mul­ tiple alternative pathways and control mechanisms exist throughout the normal sequence to limit coagulation to the area of injury and to prevent interference with the systemic circulation. Introduction RatnofP4 eloquently indicates in an arti­ cle aptly entitled: “A Tangled Web.
    [Show full text]
  • Thromboplastin, Tissue Factor
    TNF_repressed genes, fat tissue, 1 day infusion Description Accession Fold Blood Coagulation Coagulation factor III (thromboplastin, tissue factor) U07619 1.4 factor XIIIa Y12502 1.5 Cell Adhesion integrin alpha chain, H36-alpha7 X65036 1.6 integrin alpha-1 X52140 1.4 Cell Cycle Control-Cell Stress growth arrest and DNA-damage-inducible (GADD45) L32591 1.5 Cell Signaling adipocyte hormone-sensitive cyclic AMP phosphodiesterase Z22867 1.5 Fibroblast growth factor receptor 1 beta-isoform S54008 1.4 Insulin-like growth factor binding protein 6 M69055 1.9 LIM domain kinase 1 isoform 1 (LIMK-1) D31873 1.4 protein kinase PASK D88190 2.2 protein phosphatase 1 beta S78218 1.4 protein phosphatase inhibitor-1 protein J05592 1.9 S-100 beta subunit S53527 1.6 Cell Stress Glutathione S-transferase 1 (theta) D10026 1.6 heat shock related protein AI171166 1.5 selenoprotein P AI230247 1.4 Cell Structure and Cytoskeleton myosin regulatory light chain isoform C S77900 1.7 Cytokine cardiotrophin-1 D78591 1.5 Transforming growth factor, beta 3 U03491 1.8 DNA Synthesis nuclear factor I/A (NFI-A1) X84210 1.4 nuclear factor I/B (NF1-B2) AB012231 1.6 nuclear factor I/B (NF1-B3) AI176488 1.6 Immune Response mast cell protease 1 precursor (RMCP-1) U67915 1.5 MHC class II A-beta RT1.B-b-beta gene M36151 2.2 MHC class II antigen RT1.B-1 beta-chain X56596 1.8 MHC class II RT1.B-alpha chain gene X07551 2.2 MHC class II RT1.u-D-alpha chain mRNA M15562 2 MHC class II-associated invariant chain X14254 2.2 MHC RT1-B region class II (Ia antigen) K02815 1.8 MHC-associated
    [Show full text]
  • Absence of Tissue Factor Expression by Neoplastic Plasma Cells in Multiple Myeloma
    Leukemia (2012) 26, 1671 --1674 & 2012 Macmillan Publishers Limited All rights reserved 0887-6924/12 www.nature.com/leu ORIGINAL ARTICLE Absence of tissue factor expression by neoplastic plasma cells in multiple myeloma G Cesarman-Maus1, E Braggio2, H Maldonado1 and R Fonseca2 Thrombosis portends a poor prognosis in individuals with solid tumors. Constitutive expression of tissue factor (TF) by cancer cells is a key in triggering activation of coagulation and promoting aggressive tumor behavior. Though multiple myeloma (MM) is associated with a high frequency of thrombosis in the context of thalidomide and lenalidomide therapy, prognosis is not affected by its occurrence. We sought to determine the expression of TF in MM. F3 (TF gene) expression profiling was analyzed in 55 human MM cell lines (HMCL) and in 223 solid tumor cell lines obtained from GlaxoSmithKline (GSK) Cancer Cell Line Genomic Profiling Dataset. TF was not expressed in any of the 55 HMCLs studied, in sharp contrast to solid tumors, 90% of which showed TF expression. F3 expression was also absent in tumor samples from 239 MM patients. Immunohistochemistry for TF was negative, with either no or focal (1 þ ) staining in 70/73 MM patients. Only three marrow biopsies were moderately (2 þ ) positive either focally or diffusely, suggesting that in rare cases bone marrow microenvironment may support TF expression. General lack of TF expression by neoplastic plasma cells may explain why thrombosis is not predictive of poor outcome, and why aspirin prophylaxis is often effective
    [Show full text]
  • Platelet Tissue Factor Synthesis in Type 2 Diabetic Patients Is Resistant to Inhibition by Insulin Anja J
    ORIGINAL ARTICLE Platelet Tissue Factor Synthesis in Type 2 Diabetic Patients Is Resistant to Inhibition by Insulin Anja J. Gerrits,1 Cornelis A. Koekman,1 Timon W. van Haeften,2 and Jan Willem N. Akkerman1 OBJECTIVE—Patients with type 2 diabetes have an increased 2 and thrombin-antithrombin complexes, are increased. risk of cardiovascular disease and show abnormalities in the Also, the elevated levels of fibrinogen; factors (F) VII, VIII, coagulation cascade. We investigated whether increased synthe- and XI; and von Willebrand factor (VWF) might contribute sis of tissue factor (TF) by platelets could contribute to the to the prothrombotic tendency (4). In particular, circulat- hypercoagulant state. ing tissue factor (TF) is increased (5), which, as the main RESEARCH DESIGN AND METHODS—Platelets from type 2 initiator of the coagulation cascade, might contribute to diabetic patients and matched control subjects were adhered to hypercoagulability. Interestingly, improvement of glyce- different surface-coated proteins, and TF premRNA splicing, TF mic control lowers plasma TF (6). protein, and TF procoagulant activity were measured. The hyperaggregability of type 2 diabetes platelets might RESULTS—Different adhesive proteins induced different levels be caused by loss of sensitivity to insulin. Under experi- of TF synthesis. A mimetic of active clopidogrel metabolite mental conditions, platelets of type 2 diabetic patients (AR-C69931 MX) reduced TF synthesis by 56 Ϯ 10%, an aspirin- show better adhesion to a prothrombotic surface, make like inhibitor (indomethacin) by 82 Ϯ 9%, and the combination by larger aggregates, have an increased procoagulant surface, Ϯ 2ϩ 96 2%, indicating that ADP release and thromboxane A2 and have an elevated cytosolic Ca concentration com- production followed by activation of P2Y12 and thromboxane pared with platelets from healthy control subjects (7).
    [Show full text]
  • Determination of Plasma Tissue Factor Antigen and Tissue Factor-Bearing Microparticles Activity in Healthy Subjects
    Research Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2019.19.003292 Determination of Plasma Tissue Factor Antigen and Tissue Factor-Bearing Microparticles Activity in Healthy Subjects Stoencheva S1*, DenevaT1, Beleva E2, Grudeva Popova Zh2 and Popov V2 1Department of Clinical Laboratory, Bulgaria 2Department of Clinical Oncology, Bulgaria *Corresponding author: Stoencheva S, Department of Clinical Laboratory, Bulgaria ARTICLE INFO Abstract Received: June 26, 2019 Background: Tissue factor (TF) is an integral membrane protein, normally separated from the blood by the vascular endothelium, which plays a key role in the initiation of Published: July 03, 2019 blood coagulation. TF is present in plasma in various forms, including microparticles by activated or apoptotic cells. Levels of TF antigen (TF-Ag) and tissue factor-bearing Citation: Stoencheva S, Deneva T, microparticles(MPs) and alternatively (MP-TF) splicedactivity TF.from MPs different are small origins (< 1 μm) are thoughtmembrane to bevesicles associated generated with Beleva E, Grudeva Popova Zh, Popov V. hypercoagulable states. The aim of the present study was to determine the reference Determination of Plasma Tissue Factor range for plasma levels of TF-Ag and MP-TF activity in healthy subjects. Antigen and Tissue Factor-Bearing Microparticles Activity in Healthy Methods: To establish the reference range for plasma levels of TF-Ag and MP-TF Subjects. Biomed J Sci & Tech Res 19(3)- activity and study the impact of sex and age we recruited 120 healthy subjects of Bulgarian 2019. BJSTR. MS.ID.003292. nationality aged between 18 and 65. The selection criteria for the reference group were made to comply with the generally approved recommendations of the International Federation of Clinical Chemistry (IFCC).
    [Show full text]
  • Targeting Tissue Factor As a Novel Therapeutic Oncotarget For
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 1), pp: 1481-1494 Research Paper Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer Zhiwei Hu1,2, Jie Xu2,*, Jijun Cheng2,**, Elizabeth McMichael3, Lianbo Yu4, William E. Carson III1 1Department of Surgery, Division of Surgical Oncology, The Ohio State University Medical Center and The James Comprehensive Cancer Center, Columbus, OH, USA 2Yale University School of Medicine Department of Obstetrics, Gynecology and Reproductive Sciences, New Haven, CT, USA 3Biomedical Sciences Graduate Program, The Ohio State University Medical Center and The James Comprehensive Cancer Center, Columbus, OH, USA 4Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Medical Center and The James Comprehensive Cancer Center, Columbus, OH, USA *Present addresses: Institute of Cancer Stem Cell, Dalian Medical University, China **Present address: Yale University Department of Genetics, New Haven, CT, USA Correspondence to: Zhiwei Hu, email: [email protected] Keywords: cancer stem cells, solid cancer, tissue factor, targeted immunotherapy, targeted photodynamic therapy Received: October 04, 2016 Accepted: November 09, 2016 Published: November 26, 2016 ABSTRACT Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients.
    [Show full text]