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Thrombosis and Haemostasis

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https://www.readbyqxmd.com/read/28424821/noacs-for-treatment-of-venous-thromboembolism-in-clinical-practice
#1
Sam Schulman, Daniel Singer, Walter Ageno, Ivan B Casella, Marc Desch, Samuel Z Goldhaber
Randomised controlled trials have provided important information on the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of venous thromboembolism (VTE), leading to registration and increasing use in clinical practice. Many questions remain to be answered, and observational studies are often more suitable for answering "real-world" questions than randomised controlled trials. Patient satisfaction, quality of life, and adherence and persistence in clinical practice with the drug regimen can only be assessed with an open-label design...
April 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28424820/microparticles-during-long-term-follow-up-after-acute-myocardial-infarction-association-to-atherosclerotic-burden-and-risk-of-cardiovascular-events
#2
Christina Christersson, Åsa Thulin, Agneta Siegbahn
Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs) and monocytes (MMPs), and in acute myocardial infarction (MI), there is an increase of MPs in the culprit artery. In this study MPs were evaluated in whole blood in 105 patients with MI at five time-points during a two-year follow-up (FU). Patients with non-ST-elevated MI had higher concentrations of CD41+MPs compared to ST-elevated MI patients (p=0.024). The concentrations of PMPs in whole blood increased during the time period (p<0...
April 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28424819/plasma-micrornas-characterising-patients-with-immune-thrombocytopenic-purpura
#3
Bin Zuo, Juping Zhai, Lifang You, Yunxiao Zhao, Jianfeng Yang, Zhen Weng, Lan Dai, Qingyu Wu, Changgeng Ruan, Yang He
Altered microRNA (miRNA) expression has been reported in patients with immune thrombocytopenic purpura (ITP). However, the detailed expression profiling of cell-free circulating miRNAs in ITP patients has not been fully investigated. In this study, we aimed to examine plasma miRNAs in ITP patients and evaluate their diagnostic values. Plasma samples from 74 ITP patients and 58 healthy controls were obtained and allocated into discovery, validation, and therapy-response sets. Initial screen with a miRNA microarray assay identified 23 miRNAs with different levels between ITP patients and healthy controls (>1...
April 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28424818/dose-requirements-for-idarucizumab-reversal-of-dabigatran-in-a-lethal-porcine-trauma-model-with-continuous-bleeding
#4
Markus Honickel, Henri M Spronk, Rolf Rossaint, Christian Stoppe, Joanne van Ryn, Hugo Ten Cate, Oliver Grottke
Idarucizumab is licensed for emergency reversal of dabigatran. A single 5 g dose is usually sufficient, but higher doses may sometimes be required and optimum dosing has not been defined. It was the aim of this study to investigate the effect of idarucizumab, given once or as a split dose, after double trauma in pigs anticoagulated with dabigatran. Dabigatran etexilate (30 mg/kg bid) was given to 18 male pigs orally for 3 days. On day 4, animals were randomised 1:1:1 to receive idarucizumab 60+0, 60+60 or 120+0 mg/kg...
April 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405675/the-management-of-acute-venous-thromboembolism-in-clinical-practice-results-from-the-european-prefer-in-vte-registry
#5
Alexander T Cohen, Anselm K Gitt, Rupert Bauersachs, Eva-Maria Fronk, Petra Laeis, Patrick Mismetti, Manuel Monreal, Stefan N Willich, Peter Bramlage, Giancarlo Agnelli
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405673/gly74ser-mutation-in-protein-c-causes-thrombosis-due-to-a-defect-in-protein-s-dependent-anticoagulant-function
#6
Changming Chen, Likui Yang, Bruno O Villoutreix, Xuefeng Wang, Qiulan Ding, Alireza R Rezaie
Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation by thrombin in complex with thrombomodulin (TM) down-regulates the clotting cascade by a feedback loop inhibition mechanism. Activated protein C (APC) exerts its anticoagulant function through protein S-dependent degradation of factors Va and VIIIa. We recently identified a venous thrombosis patient whose plasma level of protein C antigen is normal, but its anticoagulant activity is only 34 % of the normal level. Genetic analysis revealed that the proband and her younger brother carry a novel heterozygous mutation c...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#7
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405671/predictors-of-oral-cavity-bleeding-and-clinical-outcome-after-dental-procedures-in-patients-on-vitamin-k-antagonists-a-cohort-study
#8
Joseph S Biedermann, Willem M H Rademacher, Hendrika C A M Hazendonk, Denise E van Diermen, Frank W G Leebeek, Frederik Rozema, Marieke J H A Kruip
Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1-3 elements) and extensive high-risk (e. g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after low-risk and high-risk dental procedures in patients on VKA...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405670/a-long-acting-pai-1-inhibitor-reduce-thrombus-formation
#9
Shuangzhou Peng, Guangpu Xue, Lihu Gong, Chao Fang, Jingfei Chen, Cai Yuan, Zhuo Chen, Lishan Yao, Bruce Furie, Mingdong Huang
Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activators (t/uPA) and plays an important role in the fibrinolytic system. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis, indicating that PAI-1 inhibitors may be used as effective antithrombotic agents. We previously designed a PAI-1 inhibitor (PAItrap) which is a variant of inactivated urokinase protease domain. In the present study, we tried to fuse PAItrap with human serum albumin (HSA) to develop a long-acting PAI-1 inhibitor...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382373/antagonists-of-the-system-l-neutral-amino-acid-transporter-lat-promote-endothelial-adhesivity-of-human-red-blood-cells
#10
Laura Beth Mann Dosier, Vikram J Premkumar, Hongmei Zhu, Izzet Akosman, Michael F Wempe, Timothy J McMahon
The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobin within red blood cells (RBC) has been studied, but the conduit whereby a SNO leaves the RBC remains unidentified. Here we hypothesised that SNO export by RBCs may also depend on LAT activity, and investigated the role of RBC LAT in modulating SNO-sensitive RBC-endothelial cell (EC) adhesion...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382372/mechanism-of-plasmin-generation-by-s100a10
#11
Victoria A Miller, Patricia A Madureira, Ain Adilliah Kamaludin, Jeffrey Komar, Vandna Sharma, Girish Sahni, Craig Thelwell, Colin Longstaff, David M Waisman
Plasminogen (Pg) is cleaved to form plasmin by the action of specific plasminogen activators such as the tissue plasminogen activator (tPA). Although the interaction of tPA and Pg with the surface of the fibrin clot has been well characterised, their interaction with cell surface Pg receptors is poorly understood. S100A10 is a cell surface Pg receptor that plays a key role in cellular plasmin generation. In the present report, we have utilised domain-switched/deleted variants of tPA, truncated plasminogen variants and S100A10 site-directed mutant proteins to define the regions responsible for S100A10-dependent plasmin generation...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382371/characteristics-of-dyspnoea-and-associated-clinical-outcomes-in-the-champion-phoenix-study
#12
William A Parker, Deepak L Bhatt, Jayne Prats, Jonathan R S Day, Philippe Gabriel Steg, Gregg W Stone, Christian W Hamm, Kenneth W Mahaffey, Matthew J Price, C Michael Gibson, Harvey D White, Robert F Storey
Dyspnoea may be induced by some reversibly-binding P2Y12 inhibitors, including cangrelor and ticagrelor. Dyspnoea was not associated with any compromise to the efficacy of ticagrelor in the PLATO study. The CHAMPION PHOENIX study (NCT01156571) compared initial treatment with cangrelor versus initial treatment with clopidogrel in patients undergoing PCI. We investigated the incidence, characteristics, and associated clinical outcomes in patients with dyspnoea in CHAMPION PHOENIX. Adverse events (AEs) of dyspnoea to 48 hours were recorded in patients randomised to cangrelor or clopidogrel in CHAMPION PHOENIX...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382370/impact-of-fibrinogen-carbamylation-on-fibrin-clot-formation-and-stability
#13
Veronika Binder, Brith Bergum, Stéphane Jaisson, Philippe Gillery, Carsten Scavenius, Endy Spriet, Anne Karin Nyhaug, Helen M Roberts, Iain L C Chapple, Annelie Hellvard, Nicolas Delaleu, Piotr Mydel
Carbamylation is a non-enzymatic post-translational modification induced upon exposure of free amino groups to urea-derived cyanate leading to irreversible changes of protein charge, structure and function. Levels of carbamylated proteins increase significantly in chronic kidney disease and carbamylated albumin is considered as an important biomarker indicating mortality risk. High plasma concentrations and long half-life make fibrinogen a prime target for carbamylation. As aggregation and cross-linking of fibrin monomers rely on lysine residues, it is likely that carbamylation impacts fibrinogen processing...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382369/fibrin-clot-characteristics-in-acute-ischaemic-stroke-patients-treated-with-thrombolysis-the-impact-on-clinical-outcome
#14
Jan P Bembenek, Maciej Niewada, Jakub Siudut, Krzysztof Plens, Anna Członkowska, Anetta Undas
Fibrin clot properties in acute ischaemic stroke (AIS) are unfavourably altered, including faster formation of denser and poorly lysable fibre networks. We investigated clot properties in AIS patients treated with recombinant tissue plasminogen activator (rtPA) and their impact on clinical outcome. In 74 consecutive AIS patients eligible for rtPA treatment, we assessed ex vivo plasma fibrin clot formation, permeability (Ks), and rtPA-induced lysis, along with peak thrombin generation, fibrinolysis proteins and inhibitors at three time points - on admission, after 24 hours and 3 months since stroke...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382368/on-clopidogrel-platelet-reactivity-as-predictor-for-long-term-clinical-outcome-in-patients-after-planned-discontinuation-of-clopidogrel
#15
Timo Bömicke, Christian M Valina, Christian Stratz, Michael Amann, Franz-Josef Neumann, Willibald Hochholzer
It is unknown whether the known association of high on-treatment platelet reactivity (HTPR) with worse clinical outcome in patients on clopidogrel following coronary stent implantation persists after planned discontinuation of clopidogrel. This study investigated the association of HTPR with major ischaemic events after planned discontinuation of clopidogrel. Consecutive patients undergoing elective coronary stent implantation after loading with clopidogrel 600 mg were followed for up to seven years (n=765)...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382367/von-willebrand-factor-deficiency-leads-to-impaired-blood-flow-recovery-after-ischaemia-in-mice
#16
Margreet R de Vries, Erna A B Peters, Paul H A Quax, A Yaël Nossent
Neovascularisation, i. e. arteriogenesis and angiogenesis, is an inflammatory process. Therefore attraction and extravasation of leukocytes is essential for effective blood flow recovery after ischaemia. Previous studies have shown that von Willebrand factor (VWF) is a negative regulator of angiogenesis. However, it has also been shown that VWF facilitates leukocyte attraction and extravasation. We aimed to investigate the role of VWF in arteriogenesis and angiogenesis during post-ischaemic neovascularisation...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28382366/delayed-onset-of-procoagulant-signalling-revealed-by-kinetic-analysis-of-coat-platelet-formation
#17
Lorenzo Alberio, Catherine Ravanat, Béatrice Hechler, Pierre H Mangin, François Lanza, Christian Gachet
The combined action of collagen and thrombin induces the formation of COAT platelets, which are characterised by a coat of procoagulant and adhesive molecules on their surface. Although recent work has started to highlight their clinical relevance, the exact mechanisms regulating the formation of procoagulant COAT platelets remain unclear. Therefore, we employed flow cytometry in order to visualise in real time surface and intracellular events following simultaneous platelet activation with convulxin and thrombin...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28357444/tailoring-treatment-of-haemophilia-b-accounting-for-the-distribution-and-clearance-of-standard-and-extended-half-life-fix-concentrates
#18
Alfonso Iorio, Kathelijn Fischer, Victor Blanchette, Savita Rangarajan, Guy Young, Massimo Morfini
The prophylactic administration of factor IX (FIX) is considered the most effective treatment for haemophilia B. The inter-individual variability and complexity of the pharmacokinetics (PK) of FIX, and the rarity of the disease have hampered identification of an optimal treatment regimens. The recent introduction of extended half-life recombinant FIX molecules (EHL-rFIX), has prompted a thorough reassessment of the clinical efficacy, PK and pharmacodynamics of plasma-derived and recombinant FIX. First, using longer sampling times and multi-compartmental PK models has led to more precise (and favourable) PK for FIX than was appreciated in the past...
March 30, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28357443/high-on-treatment-platelet-reactivity-as-a-risk-factor-for-adverse-left-ventricular-remodelling-after-stemi
#19
Gian Marco Podda, Marco Cattaneo
No abstract text is available yet for this article.
March 30, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28357442/mean-platelet-volume-is-associated-with-lower-risk-of-overall-and-non-vascular-mortality-in-a-general-population-results-from-the-moli-sani-study
#20
Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia de Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Larger mean platelet volume (MPV) has been associated with adverse health outcomes in high-risk populations or patients with cardiovascular disease (CVD). We tested the association of MPV with mortality in a prospective cohort study including 17,402 subjects randomly recruited from an adult general population within the Moli-sani study (2005-2010). Two distinct subgroups (with or without CVD at baseline) were subsequently analysed. Hazard ratios (HR) were calculated using multivariable Cox-proportional hazard models...
March 30, 2017: Thrombosis and Haemostasis
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