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https://www.readbyqxmd.com/read/28102740/update-on-functional-and-genetic-laboratory-assays-for-the-detection-of-platelet-microvesicles
#1
Maxime Laroche, Claire Dunois, Anne Marie Vissac, Jean Amiral
Functional and genetic assays for measuring platelet microvesicles (PMVs) are presented and discussed. Functional assays concern two groups of methods: a) homogeneous assays using the cofactor activity of phospholipids (PPLs) contained in PMVs and present in assayed plasmas, and a coagulation or a thrombin generation assay (TGA) as "end points"; b) capture-based assays, in which PMVs bind to an immobilized ligand, such as Annexin V in the presence of calcium, or monoclonal antibodies (MoAbs) specific for membrane proteins...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28098698/clinical-and-practical-aspects-of-restoring-thrombin-generation-in-acute-coagulopathic-bleeding
#2
Kenichi A Tanaka, Daniel Bolliger, Nina A Guzzetta
No abstract text is available yet for this article.
February 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#3
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28095402/a-general-shear-dependent-model-for-thrombus-formation
#4
Alireza Yazdani, He Li, Jay D Humphrey, George Em Karniadakis
Modeling the transport, activation, and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions. We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro experimental data and can be used over a wide range of flow shear rates ([Formula: see text]). We introduce an Eulerian-Lagrangian model where hemodynamics is solved on a fixed Eulerian grid, while platelets are tracked using a Lagrangian framework...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28090594/effects-of-tranexamic-acid-on-platelet-function-and-thrombin-generation-etaplat-woman-trial-sub-study
#5
Kastriot Dallaku, Haleema Shakur, Ian Roberts, Phil Edwards, Danielle Beaumont, Maria Delius, Braun Siegmund, Orion Gliozheni, Ilir Tasha, Saimir Cenameri, Ulrich Mansmann
Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets.  Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH.  Methods. We will conduct a sub-study within the WOMAN trial...
December 15, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28088496/endogenous-thrombin-potential-changes-during-the-first-cycle-of-oral-contraceptive-use
#6
Carolyn L Westhoff, Malcolm C Pike, Serge Cremers, Andrew Eisenberger, Stella Thomassen, Jan Rosing
OBJECTIVES: Venous thromboembolism (VTE) risk increases within months of combination oral contraceptive (COC) initiation. Because elevated endogenous thrombin potential (ETP) has been found in several studies to be a VTE risk factor, we evaluated the extent of ETP changes during the initial cycle of an ethinyl estradiol (EE) and levonorgestrel (LNG) COC. We also assessed the relationship between ETP changes and systemic EE and LNG concentrations. STUDY DESIGN: Participants provided multiple blood samples during a first 21-day cycle of a 30 μg EE/150 μg LNG COC and after a further 7 days without an active COC...
January 11, 2017: Contraception
https://www.readbyqxmd.com/read/28074413/procoagulant-activity-of-extracellular-vesicles-as-a-potential-biomarker-for-risk-of-thrombosis-and-dic-in-patients-with-acute-leukaemia
#7
Gheldof Damien, Haguet Hélène, Dogné Jean-Michel, Bouvy Céline, Graux Carlos, George Fabienne, Sonet Anne, Chatelain Christian, Chatelain Bernard, Mullier François
Haemostatic complication is common for patients with hematologic malignancies. Recent studies suggest that the procoagulant activity (PCA) of extracellular vesicles (EV) may play a major role in venous thromboembolism and disseminated intravascular coagulation (DIC) in acute leukaemia. To study the impact of EVs from leukaemic patients on thrombin generation and to assess EV-PCA as a potential biomarker for thrombotic complications in patients with acute leukaemia. Blood samples from a cohort of patients with newly diagnosed acute leukaemia were obtained before treatment (D-0), 3 and 7 days after treatment (D-3 and D-7)...
January 10, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28069606/proteolytic-properties-of-single-chain-factor-xii-a-mechanism-for-triggering-contact-activation
#8
Ivan Ivanov, Anton Matafonov, Mao-Fu Sun, Qiufang Cheng, S Kent Dickeson, Ingrid M Verhamme, Jonas Emsley, David Gailani
When blood is exposed to variety of artificial surfaces and biologic substances, the plasma proteins factor XII (FXII) and prekallikrein undergo reciprocal proteolytic conversion to the proteases αFXIIa and α-kallikrein by a process called contact activation. These enzymes contribute to host-defense responses including coagulation, inflammation, and fibrinolysis. The initiating event in contact activation is debated. To test the hypothesis that single-chain FXII expresses activity that could initiate contact activation, we prepared human FXII variants lacking the Arg353 cleavage site required for conversion to αFXIIa (FXII-R353A), or lacking the three known cleavage sites at Arg334, Arg343, and Arg353 (FXII-T, for "triple" mutant), and compared their properties to wild type αFXIIa...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28064371/thrombin-generation-measurements-in-patients-scheduled-for-laparoscopic-bariatric-surgery
#9
Jérémie Thereaux, Fanny Mingant, Charles Roche, Hubert Galinat, Francis Couturaud, Karine Lacut
PURPOSE: Obese patients are known to be in an in vitro hypercoagulable state relative to normal-weight patients. Our study aimed to identify markers of enhanced coagulability (endogenous thrombin potential (ETP)) in morbidly obese patients using the thrombin generation (TG) test. MATERIALS AND METHODS: All patients scheduled for laparoscopic bariatric surgery (LBS) between September 1, 2014 and January 31, 2016 were eligible for our prospective study. We used logistic regression to compute the odds ratio (OR) across ETP quartile distributions to evaluate the risk of enhanced TG...
January 7, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28060970/-evaluation-of-oral-anticoagulation-with-rivaroxaban-in-patients-with-new-onset-non-valvular-atrial-fibrillation
#10
Víctor Neira, Ramón Corbalán, Jaime Pereira, Olga Panes, Bernardita Garayar, Andrés Aizman, Silvana Llevaneras, Luis Villarroel
BACKGROUND: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. AIM: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. PATIENTS AND METHODS: Prospective study in patients with indication of anticoagulation...
September 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28058802/increased-thrombin-generation-in-a-mouse-model-of-cancer-cachexia-is-partially-interleukin-6-dependent
#11
Caroline J Reddel, John D Allen, Anahid Ehteda, Ryland Taylor, Vivien M Y Chen, Jennifer L Curnow, Leonard Kritharides, Graham Robertson
BACKGROUND: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. OBJECTIVES: To assess if cancer cachexia altered coagulation state and if this was attributable to tumor IL-6 production...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#12
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28042854/in-vitro-anti-thrombotic-activity-of-extracts-from-blacklip-abalone-haliotis-rubra-processing-waste
#13
Hafiz Ansar Rasul Suleria, Barney M Hines, Rama Addepalli, Wei Chen, Paul Masci, Glenda Gobe, Simone A Osborne
Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity...
December 31, 2016: Marine Drugs
https://www.readbyqxmd.com/read/28038846/primary-prophylaxis-for-children-with-severe-congenital-factor-vii-deficiency-clinical-and-laboratory-assessment
#14
A A Kuperman, A A Barg, Y Fruchtman, E Shaoul, N Rosenberg, G Kenet, T Livnat
Severe congenital factor VII (FVII) deficiency is a rare bleeding disorder. Prophylaxis with replacement therapy has been suggested to patients, yet the most beneficial dosing regimens and therapy intervals are still to be defined. Due to the lack of evidence-based data, we hereby present our experience with long-term administration and monitoring primary prophylaxis in children with severe FVII deficiency and an extremely high bleeding risk. Four children with familial FVII deficiency, treated by prophylactic recombinant activated factor VII (rFVIIa), 15-30μg/kg/dose, given 2-3 times weekly since infancy, are discussed...
December 19, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28032527/bioreactivity-of-stent-material-activation-of-platelets-coagulation-leukocytes-and-endothelial-cell-dysfunction-in-vitro
#15
Veronique Ollivier, Caroline Roques, Nicolas Receveur, Matthias Gratz, Laurent Feldman, Didier Letourneur, Christian Gachet, Pierre H Mangin, Martine Jandrot-Perrus
Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28029716/inactivation-of-human-coagulation-factor-x-by-a-protease-of-the-pathogen-capnocytophaga-canimorsus
#16
K Hack, F Renzi, E Hess, F Lauber, J Douxfils, J M Dogné, G R Cornelis
BACKGROUND: Capnocytophaga canimorsus is a Gram-negative bacterium, which belongs to the oral flora of dogs and causes fulminant sepsis in humans who have been bitten, licked or scratched. In patients, bleeding abnormalities, such as petechiae, purpura fulminans or disseminated intravascular coagulation (DIC) occur frequently. OBJECTIVE: We investigated whether C. canimorsus could actively contribute to these bleeding abnormalities. METHODS: Calibrated automated thrombogram and clotting time assays were performed to assess the anticoagulant activity of C...
December 28, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28029283/evaluation-of-procoagulant-tissue-factor-expression-in-canine-hemangiosarcoma-cell-lines
#17
Lauren E Witter, Erika J Gruber, Fabian Z X Lean, Tracy Stokol
OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor-replete or specific coagulation factor-deficient human plasma by calibrated automated thrombography...
January 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28024915/how-do-megakaryocytic-microparticles-target-and-deliver-cargo-to-alter-the-fate-of-hematopoietic-stem-cells
#18
Jinlin Jiang, Chen-Yuan Kao, Eleftherios T Papoutsakis
Megakaryocytic microparticles (MkMPs), the most abundant MPs in circulation, can induce the differentiation of hematopoietic stem and progenitor cells (HSPCs) into functional megakaryocytes. This MkMP capability could be explored for applications in transfusion medicine but also for delivery of nucleic acids and other molecules to HSPCs for targeted molecular therapy. Understanding how MkMPs target, deliver cargo and alter the fate of HSPCs is important for exploring such applications. We show that MkMPs, which are distinct from Mk exosomes (MkExos), target HSPCs with high specificity since they have no effect on other ontologically or physiologically related cells, namely mesenchymal stem cells, endothelial cells or granulocytes...
December 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28024455/the-neisseria-meningitidis-lpxl1-mutant-induces-less-tissue-factor-expression-and-activity-in-primary-human-monocytes-and-monocyte-derived-microvesicles-than-the-wild-type-meningococcus
#19
Marit Hellum, Anne-Marie S Trøseid, Jens P Berg, Petter Brandtzaeg, Reidun Øvstebø, Carola E Henriksson
Neisseria meningitidis (N. meningitidis) may cause sepsis and meningitis. N. meningitidis with a mutated lpxL1 gene has five, instead of six, acyl chains in the lipid A moiety. Compared with patients infected with the wild type (wt) meningococcus, patients infected with the lpxL1 mutant have a mild meningococcal disease with less systemic inflammation and less coagulopathy. Circulating tissue factor (TF), the main initiator of coagulation, has a central role in the development of coagulation disturbances during sepsis...
January 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/28009236/increased-blood-cell-phosphatidylserine-exposure-and-circulating-microparticles-contribute-to-procoagulant-activity-after-carotid-artery-stenting
#20
Lu Zhao, Xiaoming Wu, Yu Si, Zhipeng Yao, Zengxiang Dong, Valerie A Novakovic, Li Guo, Dongxia Tong, He Chen, Yayan Bi, Junjie Kou, Huaizhang Shi, Ye Tian, Shaoshan Hu, Jin Zhou, Jialan Shi
OBJECTIVE Phosphatidylserine (PS) is a major component of the inner leaflet of membrane bilayers. During cell activation or apoptosis, PS is externalized to the outer membrane, providing an important physiological signal necessary for the release of the microparticles (MPs) that are generated through the budding of cellular membranes. MPs express PS and membrane antigens that reflect their cellular origin. PS exposure on the cell surface and the release of MPs provide binding sites for factor Xa and prothrombinase complexes that promote thrombin formation...
December 23, 2016: Journal of Neurosurgery
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