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Thrombosis and Haemostasis

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https://www.readbyqxmd.com/read/28203685/sgk1-up-regulates-orai1-expression-and-vsmc-migration-during-neointima-formation-after-arterial-injury
#1
Britta Walker-Allgaier, Malte Schaub, Ioana Alesutan, Jakob Voelkl, Sascha Geue, Patrick Münzer, José M Rodríguez, Dietmar Kuhl, Florian Lang, Meinrad Gawaz, Oliver Borst
No abstract text is available yet for this article.
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28203684/crushed-sublingual-versus-oral-ticagrelor-administration-strategies-in-patients-with-unstable-angina-a-pharmacokinetic-pharmacodynamic-study
#2
Piotr Niezgoda, Joanna Sikora, Malwina Barańska, Adam Sikora, Katarzyna Buszko, Emilia Siemińska, Michał Piotr Marszałł, Jolanta M Siller-Matula, Bernd Jilma, Dimitrios Alexopoulos, Tomasz Fabiszak, Jacek Kubica
Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28203683/identification-of-unique-venous-thromboembolism-susceptibility-variants-in-african-americans
#3
John A Heit, Sebastian M Armasu, Bryan M McCauley, Iftikhar J Kullo, Hugues Sicotte, Jyotishman Pathak, Christopher G Chute, Omri Gottesman, Erwin P Bottinger, Joshua C Denny, Dan M Roden, Rongling Li, Marylyn D Ritchie, Mariza de Andrade
To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28203682/jam-c-maintains-vegr2-expression-to-promote-retinal-pigment-epithelium-cell-survival-under-oxidative-stress
#4
Xin Jia, Chen Zhao, Qishan Chen, Yuxiang Du, Lijuan Huang, Zhimin Ye, Xiangrong Ren, Shasha Wang, Chunsik Lee, Zhongshu Tang, Xuri Li, Rong Ju
Junctional adhesion molecule-C (JAM-C) has been shown to play critical roles during development and in immune responses. However, its role in adult eyes under oxidative stress remains poorly understood. Here, we report that JAM-C is abundantly expressed in adult mouse retinae and choroids in vivo and in cultured retinal pigment epithelium (RPE) and photoreceptor cells in vitro. Importantly, both JAM-C expression and its membrane localisation are downregulated by H2O2-induced oxidative stress. Under H2O2-induced oxidative stress, JAM-C is critically required for the survival of human RPE cells...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28203681/small-but-mighty-platelets-as-central-effectors-of-host-defense
#5
Thomas J Stocker, Hellen Ishikawa-Ankerhold, Steffen Massberg, Christian Schulz
Platelets actively participate in inflammatory processes and drive diseases such as atherosclerosis, rheumatoid arthritis and cancer metastasis. However, platelets also have anti-inflammatory and anti-infective properties, which have received less consideration in the past. In this review, we highlight recent findings on the role of platelets in host defense and describe regulatory pathways modulating immune responses. Furthermore, we discuss the role of platelets for the resolution of inflammation and tissue repair...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28180235/incidence-rates-and-case-fatality-rates-of-portal-vein-thrombosis-and-budd-chiari-syndrome
#6
Walter Ageno, Francesco Dentali, Fulvio Pomero, Luigi Fenoglio, Alessandro Squizzato, Giovanni Pagani, Roberta Re, Matteo Bonzini
Little information is available on the incidence of splanchnic vein thrombosis and on mortality rates during the acute phase of the disease. We performed a large epidemiologic study on hospital admissions for portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BCS) between 2002 and 2012 in Northwestern Italy. Primary and secondary discharge diagnoses of PVT and BCS were identified using the 9th edition International Classification of Diseases codes 453.0, 572.1 and 452. Hospitalisations for recurrent events were not included...
February 9, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28180234/pharmacokinetics-and-pharmacodynamics-of-tecarfarin-a-novel-vitamin-k-antagonist-oral-anticoagulant
#7
Detlef Albrecht, David Ellis, Daniel M Canafax, Daniel Combs, Pascal Druzgala, Peter G Milner, Mark G Midei
Tecarfarin is a vitamin K antagonist (VKA) with reduced propensity for drug interactions. To evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety of tecarfarin, we performed single ascending dose (SAD) (n=66), multiple ascending dose (MAD) (n=43), and tecarfarin versus warfarin (n=28) studies in human volunteers. In the SAD, tecarfarin was administered to 5 of 6 subjects (1 received placebo) in each of 11 cohorts. AUC0-∞ exhibited linearity and dose proportionality. Elimination T1/2 ranged from 87-136 hours (h) across all doses...
February 9, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28180233/abnormal-vaginal-bleeding-in-women-with-venous-thromboembolism-treated-with-apixaban-or-warfarin
#8
Marjolein P A Brekelmans, Luuk J J Scheres, Suzanne M Bleker, Barbara A Hutten, Anne Timmermans, Harry R Büller, Saskia Middeldorp
Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin...
February 9, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28151543/prediction-of-major-and-clinically-relevant-bleeding-in-patients-with-vte-treated-with-edoxaban-or-vitamin-k-antagonists
#9
Marcello Di Nisio, Gary Raskob, Harry R Büller, Michael A Grosso, George Zhang, Shannon M Winters, Alexander Cohen
Better understanding of risk factors for major bleeding events during anticoagulant treatment for venous thromboembolism (VTE) may help physicians when deciding on intensity and duration of treatment. The primary aim of this study was to identify risk factors for major and clinically relevant bleeding in patients receiving the oral factor Xa inhibitor edoxaban or warfarin for the treatment of acute VTE. We analysed data from 8240 patients who received ≥1 dose of study drug in the Hokusai-VTE study. Bleeding risk factors were evaluated in 4118 patients who received edoxaban and significant variables were combined in a prediction model...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150855/fibrin-clot-structure-pro-fibrinolytic-effect-of-oral-contraceptives-in-apparently-healthy-women
#10
Johannes J Sidelmann, Cornelis Kluft, Andrea H Krug, Ulrich Winkler, Jørgen Jespersen, Jørgen B Gram
Fibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150854/imaging-analyses-of-coagulation-dependent-initiation-of-fibrinolysis-on-activated-platelets-and-its-modification-by-thrombin-activatable-fibrinolysis-inhibitor
#11
Tomasz Brzoska, Yuko Suzuki, Hideto Sano, Seiichirou Suzuki, Martyna Tomczyk, Hiroki Tanaka, Tetsumei Urano
Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the center of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150853/performance-of-the-20-minute-whole-blood-clotting-test-in-detecting-venom-induced-consumption-coagulopathy-from-russell-s-viper-daboia-russelii-bites
#12
Indira Ratnayake, Fathima Shihana, Dhammika M Dissanayake, Nicholas A Buckley, Kalana Maduwage, Geoffrey K Isbister
The 20-minute whole blood clotting test (WBCT20) is used as a bedside diagnostic test for coagulopathic snake envenoming. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell's viper envenoming. Adult patients admitted with suspected snake bites were recruited from two hospitals. WBCT20 and prothrombin time (PT) test were performed on admission. WBCT20 was done by trained clinical research assistants using 1 ml whole blood in a 5 ml borosilicate glass tube with a 10 mm internal diameter...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150852/novel-role-of-platelet-reactivity-in-adverse-left-ventricular-remodelling-after-st-segment-elevation-myocardial-infarction-the-remodeling-trial
#13
Yongwhi Park, Udaya S Tantry, Jin-Sin Koh, Jong-Hwa Ahn, Min Gyu Kang, Kye Hwan Kim, Jeong Yoon Jang, Hyun Woong Park, Jeong-Rang Park, Seok-Jae Hwang, Ki-Soo Park, Choong Hwan Kwak, Jin-Yong Hwang, Paul A Gurbel, Young-Hoon Jeong
The role of platelet-leukocyte interaction in the infarct myocardium still remains unveiled. We aimed to determine the linkage of platelet activation to post-infarct left ventricular remodelling (LVR) process. REMODELING was a prospective, observational, cohort trial including patients (n = 150) with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Patients were given aspirin plus clopidogrel therapy (600 mg loading and 75 mg daily). Platelet reactivity (PRU: P2Y12 Reaction Units) was assessed with VerifyNow P2Y12 assay on admission...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150851/risk-assessment-models-for-venous-thromboembolism-in-acutely-ill-medical-patients-a-systematic-review
#14
Anna K Stuck, David Spirk, Jil Schaudt, Nils Kucher
Although the use of thromboprophylaxis is recommended for acutely ill medical patients at increased risk of venous thromboembolism (VTE), it remains unclear which risk assessment model (RAM) should be routinely used to identify at-risk patients requiring thromboprophylaxis. We therefore aimed to describe existing RAMs, and to compare these tools in terms of validity and applicability for clinical decision-making. We performed a comprehensive systematic search in MEDLINE from the date of initiation until May 2016 for studies in acutely ill medical patients investigating validity of RAMs for VTE...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150850/chewing-versus-swallowing-ticagrelor-to-accelerate-platelet-inhibitionin-acute-coronary-syndrome-the-cheers-study-for-the-platis-platelets-and-thrombosis-in-sheba-study-group
#15
Elad Asher, Shir Frydman, Moshe Katz, Ehud Regev, Avi Sabbag, Israel Mazin, Arsalan Abu-Much, Andrew Kukuy, Anna Mazo, Aharon Erez, Anat Berkovitch, Michael Narodistky, Israel Barbash, Amit Segev, Roy Beigel, Shlomi Matetzky
It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28150849/from-thrombosis-to-fibrosis-in-chronic-thromboembolic-pulmonary-hypertension
#16
Magdalena L Bochenek, Nico S Rosinus, Mareike Lankeit, Lukas Hobohm, Felix Bremmer, Eva Schütz, Frederikus A Klok, Sven Horke, Christoph B Wiedenroth, Thomas Münzel, Irene M Lang, Eckhard Mayer, Stavros Konstantinides, Katrin Schäfer
The pathomechanisms underlying the development of thrombofibrotic pulmonary artery occlusions in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) are largely unknown. The aim of this study was to allocate distinct cellular processes playing a role in thrombus resolution, such as inflammation, hypoxia, proliferation, apoptosis and angiogenesis, to different stages of thrombofibrotic remodelling. A total of 182 pulmonary endarterectomy (PEA) specimens were collected from 31 CTEPH patients. To facilitate co-localisation, Tissue MicroArrays were prepared and processed for (immuno)-histochemistry and confocal fluorescence microscopy...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28124063/nucleic-acids-as-cofactors-for-factor-xi-and-prekallikrein-activation-different-roles-for-high-molecular-weight-kininogen
#17
Ivan Ivanov, Mao-Fu Sun, S Kent Dickeson, Cristina Puy, Owen J T McCarty, Andras Gruber, Anton Matafonov, David Gailani
The plasma zymogens factor XI (fXI) and prekallikrein (PK) are activated by factor XIIa (fXIIa) during contact activation. Polyanions such as DNA and RNA may contribute to thrombosis and inflammation partly by enhancing PK and fXI activation. We examined PK and fXI activation in the presence of nucleic acids, and determine the effects of the cofactor high molecular weight kininogen (HK) on the reactions. In the absence of HK, DNA and RNA induced of fXI autoactivation. Proteases known to activate fXI (fXIIa and thrombin) did not enhance this process appreciably...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28124061/microfluidic-coagulation-assay-for-monitoring-anticoagulant-therapy-in-acute-stroke-patients
#18
Annemarie Bluecher, Sascha Meyer Dos Santos, Nerea Ferreirós, Sandra Labocha, Isabel Maria Rodrigues Meyer Dos Santos, Bettina Picard-Willems, Sebastian Harder, Oliver C Singer
Reliable detection of anticoagulation status in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) is challenging but of importance especially in the emergency setting. This study evaluated the potential of a whole-blood clotting time assay based on Surface Acoustic Waves (SAW-CT) in stroke-patients. The SAW-technology was used for quick and homogenous recalcification of whole blood inducing a surface-activated clotting reaction quantified and visualised by real-time fluorescence microscopy with automatic imaging processing...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28124060/bone-morphogenetic-protein-4-regulates-micrornas-mir-494-and-mir-126-5p-in-control-of-endothelial-cell-function-in-angiogenesis
#19
Jennifer S Esser, Erika Saretzki, Franziska Pankratz, Bianca Engert, Sebastian Grundmann, Christoph Bode, Martin Moser, Qian Zhou
MicroRNAs are small non-coding RNAs that negatively regulate posttranscriptional gene expression. Several microRNAs have been described to regulate the process of angiogenesis. Previously, we have shown that bone morphogenetic protein 4 (BMP4) increased the pro-angiogenic activity of endothelial cells. In this project, we now investigated how the pro-angiogenic BMP4 effect is mediated by microRNAs. First, we performed a microRNA array with BMP4-stimulated human umbilical vein endothelial cells (HUVECs). Among the top-regulated microRNAs, we detected a decreased expression of miR-494 and increased expression of miR-126-5p...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28102428/plasma-adamts13-activity-and-von-willebrand-factor-antigen-and-activity-in-patients-with-subarachnoid-haemorrhage
#20
Monisha Kumar, Wenjing Cao, Jenny K McDaniel, Huy P Pham, Dheeraj Raju, Kelsey Nawalinski, Suzanne Frangos, David Kung, Eric Zager, Scott E Kasner, Joshua M Levine, X Long Zheng
Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). It was our objective to determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Forty consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls...
January 19, 2017: Thrombosis and Haemostasis
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