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Thrombosis and Haemostasis

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https://www.readbyqxmd.com/read/28536722/apixaban-pharmacodynamic-activity-in-umbilical-cord-paediatric-and-adult-plasma
#1
Robert J Yetman, Yu Chen Barrett, Zhaoqing Wang, Robert Adamczyk, Jessie Wang, Eduardo Ramacciotti, Charles Frost
The objective was to characterise apixaban pharmacodynamic (PD) activity in umbilical cord (UC), paediatric, and adult plasma. Plasma was obtained from blood samples from six UC donors, 70 paediatric (neonates [birth-≤1 month], infants [>1-≤6 months], toddlers [>6 months-≤2 years], young children [>2-≤6 years], children [>6-≤12 years], adolescents [>12-≤18 years]), and six adult (19-45 years) subjects. Plasma spiked with apixaban 0 (baseline), 30, or 110 ng/ml was analysed for anti-factor Xa activity, factor X levels, prothrombin time (PT), and modified PT (mPT)...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28536721/differential-integrin-activity-mediated-by-platelet-collagen-receptor-engagement-under-flow-conditions
#2
Nicholas Pugh, Ben D Maddox, Dominique Bihan, Kirk A Taylor, Martyn P Mahaut-Smith, Richard W Farndale
The platelet receptors glycoprotein (Gp)VI, integrin α2β1 and GpIb/V/IX mediate platelet adhesion and activation during thrombogenesis. Increases of intracellular Ca(2+) ([Ca(2+)]i) are key signals during platelet activation; however, their relative importance in coupling different collagen receptors to functional responses under shear conditions remains unclear. To study shear-dependent, receptor-specific platelet responses, we used collagen or combinations of receptor-specific collagen-mimetic peptides as substrates for platelet adhesion and activation in whole human blood under arterial flow conditions and compared real-time and endpoint parameters of thrombus formation alongside [Ca(2+)]i measurements using confocal imaging...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28536720/prostaglandin-endoperoxide-synthase-2-deletion-affects-the-natural-trafficking-of-annexin-a2-in-monocytes-and-favours-venous-thrombosis-in-mice
#3
Patrizia Amadio, Eva Tarantino, Leonardo Sandrini, Elena Tremoli, Silvia S Barbieri
Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predisposes to venous thrombosis as suggested by greater clot firmness and clot elasticity, by higher plasma levels of functional fibrinogen, factor VIII and PAI-1 activity, and proved by bigger thrombi detected after inferior vena cava ligation (IVCL) compared to WT mice...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28536718/molecular-and-clinical-profile-of-vwd-in-a-large-cohort-of-chinese-population-application-of-next-generation-sequencing-and-cnvplex-%C3%A2-technique
#4
Qian Liang, Huanhuan Qin, Qiulan Ding, Xiaoling Xie, Runhui Wu, Hongli Wang, Yiqun Hu, Xuefeng Wang
Von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency, heterogeneous laboratory phenotype and race specific distribution of mutations. The present study aimed to determine the correlation of genotype and phenotype in 200 Chinese individuals from 90 unrelated families with VWD. Next generation sequencing (NGS) of the whole coding VWF, copy number analysis of VWF by CNVplex® technique as well as a comprehensive phenotypic assessment were carried out in all index patients (IPs)...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28536717/increased-risks-of-venous-thromboembolism-in-patients-with-psoriasis-a-nationwide-cohort-study
#5
Wei-Sheng Chung, Cheng-Li Lin
Systemic inflammation and hypercoagulability in psoriasis are related to cardiovascular morbidity. The aim of the study was to investigate the incidence and risk of venous thromboembolism (VTE) in patients with psoriasis in Taiwan. We identified inpatients aged ≥ 18 years with a diagnosis of psoriasis and controls at a 1: 1 ratio of frequency matched by sex, age, frequency of medical visits, length of stay, and comorbidities between 2000 and 2010 in the Taiwan National Health Insurance Research Database. Each patient was traced to the date of VTE occurrence, loss to follow-up, death, or the December 31, 2011, whichever occurred first...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28517021/low-discriminating-power-of-the-modified-ottawa-vte-risk-score-in-a-cohort-of-patients-with-cancer-from-the-riete-registry
#6
Adriano Alatri, Lucia Mazzolai, Carme Font, Alfonso Tafur, Reina Valle, Pablo Javier Marchena, Aitor Ballaz, Eros Tiraferri, Llorenç Font, Manuel Monreal
Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41 %) at intermediate risk, and 4,255 (38 %) at high risk...
May 18, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492702/low-plasma-fvii-c-and-activated-fvii-as-predictive-markers-for-overt-disseminated-intravascular-coagulation
#7
Surapong Lertthammakiat, Nattachai Anantasit, Usanarat Anurathapan, Nongnuch Sirachainan, Praguywan Kadegasem, Ampaiwan Chuansumrit
In sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with tissue factor is the key step of coagulation resulting in disseminated intravascular coagulation (DIC). We conducted a prospective cohort study among 47 septic patients, aged 8 months to 18.8 years. They were initially divided into three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57 % (interquartile range [IQR] 41-80)] and overt DIC groups [33 % (23-52)] than that in the no DIC group [65 % (44-87)]...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492701/short-term-intensive-training-attenuates-the-exercise-induced-interaction-of-mono-1-2-cells-and-platelets-after-coronary-bypass-in-cardiac-patients
#8
Shu-Chun Huang, Mei-Kuen Wong, Pyng-Jing Lin, Feng-Chun Tsai, Jaw-Ji Chu, Meng-Yu Wu, Tieh-Cheng Fu, Jong-Shyan Wang
The interaction between platelets and monocytes plays a critical role in the pathogenesis and progression of cardiovascular diseases. This study investigated how short-term intensive training (SIT) influences monocyte subset characteristics and exercise-induced monocyte and platelet aggregates (MPAs) following elective coronary bypass (CABG) in cardiac patients. Forty-nine patients hospitalised for CABG were randomised into SIT (N=26) and conventional training (CT, N=23) groups. The SIT subjects underwent supervised aerobic training at 80~120 % of the ventilatory anaerobic threshold based on sub-maximal exercise tests performed 7 days post-CABG for 20 sessions with two sessions/day and 30 min/session, which were completed within four weeks after surgery...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492700/coagulation-factor-xi-improves-host-defence-during-murine-pneumonia-derived-sepsis-independent-of-factor-xii-activation
#9
Ingrid Stroo, Sacha Zeerleder, Chao Ding, Brenda M Luken, Joris J T H Roelofs, Onno J de Boer, Joost C M Meijers, Francis J Castellino, Cornelis van 't Veer, Tom van der Poll
Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved in host defence during pneumonia and whether this is dependent on FXII activation, we infected in parallel wild-type (WT), FXI knockout (KO) and FXII KO mice with two different clinically relevant pathogens, the Gram-positive bacterium Streptococcus pneumoniae and the Gram-negative bacterium Klebsiella pneumoniae, via the airways...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492699/lipopolysaccharide-as-trigger-of-platelet-aggregation-via-eicosanoid-over-production
#10
Cristina Nocella, Roberto Carnevale, Simona Bartimoccia, Marta Novo, Roberto Cangemi, Daniele Pastori, Camilla Calvieri, Pasquale Pignatelli, Francesco Violi
The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp)...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492698/il-33-stimulates-the-release-of-procoagulant-microvesicles-from-human-monocytes-and-differentially-increases-tissue-factor-in-human-monocyte-subsets
#11
Stefan Stojkovic, Åsa Thulin, Lena Hell, Barbara Thaler, Sabine Rauscher, Johanna Baumgartner, Marion Gröger, Cihan Ay, Svitlana Demyanets, Christoph Neumayer, Ihor Huk, Andreas Spittler, Kurt Huber, Johann Wojta, Agneta Siegbahn, Mikael Åberg
Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492697/cd32-inhibition-and-high-dose-of-rhfviii-suppress-murine-fviii-specific-recall-response-by-distinct-mechanisms-in-vitro
#12
Nadine Vollack, Julia Friese, Sabine Bergmann, Andreas Tiede, Sonja Werwitzke
Development of neutralising antibodies (inhibitors) against factor VIII (FVIII) is a frequent and severe complication of replacement therapy in haemophilia A. Previous data from haemophilia A mouse model demonstrates that both CD32 inhibition and high doses of rhFVIII prevent the differentiation of FVIII-specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here, cellular targets responsible for the suppression of ASC formation by means of CD32 inhibition and high dose of rhFVIII were analysed...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492696/complex-recombination-with-deletion-in-the-f8-and-duplication-in-the-tmlhe-mediated-by-int22h-copies-during-early-embryogenesis
#13
Changming Chen, Xiaoling Xie, Xi Wu, Yeling Lu, Xuefeng Wang, Wenman Wu, Yiqun Hu, Qiulan Ding
Haemophilia A (HA) is a common X-linked recessive bleeding disorder and almost one half of patients with severe HA are caused by intron 22 inversion (Inv22) in the F8. Inv22 is considered to be almost exclusively of meiotic origin in germ cells during spermatogenesis and only one mosaic Inv22 female carrier with the mutation possibly occurring during mitosis of the embryo has been reported so far. Previously we have identified a novel complex recombination mediated by int22h copies in a sporadic severe HA pedigree and herein we have localised the sequences flanking the breakpoint region using genome walking technique, AccuCopy technique, gene chip and real-time PCR...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28492695/joint-assessment-in-von-willebrand-disease-validation-of-the-haemophilia-joint-health-score-and-haemophilia-activities-list
#14
Karin P M van Galen, Merel A Timmer, Piet de Kleijn, Kathelijn Fischer, Wouter Foppen, Roger E G Schutgens, Jeroen Eikenboom, Karina Meijer, Marjon H Cnossen, Karin Fijnvandraat, Johanna G van der Bom, Britta A P Laros-van Gorkom, Frank W G Leebeek, Eveline P Mauser-Bunschoten
Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and reliability of the Haemophilia Joint Health Score (HJHS) and Haemophilia Activities List (HAL) in patients with Von Willebrand disease (VWD). Ninety-six patients with VWD were included (mean age 46 years) of whom 27 had more than five documented joint bleeds...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28451690/factor-viiia-mimetic-cofactor-activity-of-a-bispecific-antibody-to-factors-ix-ixa-and-x-xa-emicizumab-depends-on-its-ability-to-bridge-the-antigens
#15
Takehisa Kitazawa, Keiko Esaki, Tatsuhiko Tachibana, Shinya Ishii, Tetsuhiro Soeda, Atsushi Muto, Yoshiki Kawabe, Tomoyuki Igawa, Hiroyuki Tsunoda, Keiji Nogami, Midori Shima, Kunihiro Hattori
Emicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a manner similar to FVIIIa. However, details of the emicizumab-antigen interactions have not been reported so far. In this study, we first showed by surface plasmon resonance analysis that emicizumab bound FIX, FIXa, FX, and FXa with moderate affinities (KD = 1.58, 1.52, 1.85, and 0.978 µM, respectively). We next showed by immunoblotting analysis that emicizumab recognised the antigens' epidermal growth factor (EGF)-like domains...
April 28, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28447710/khorana-score-and-histotype-predicts-incidence-of-early-venous-thromboembolism-in-non-hodgkin-lymphomas-a-pooled-data-analysis-of-12-clinical-trials-of-fondazione-italiana-linfomi-fil
#16
Roberto Mario Santi, Manuela Ceccarelli, Elisa Bernocco, Chiara Monagheddu, Andrea Evangelista, Federica Valeri, Federico Monaco, Umberto Vitolo, Sergio Cortelazzo, Maria Giuseppina Cabras, Michele Spina, Luca Baldini, Carola Boccomini, Annalisa Chiappella, Alessia Bari, Stefano Luminari, Carlo Visco, Marco Calabrese, Giulia Limberti, Alessandro Levis, Laura Contino, Giovannino Ciccone, Marco Ladetto
Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs...
April 27, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28447100/f7-gene-variants-modulate-protein-levels-in-a-large-cohort-of-patients-with-factor-vii-deficiency-results-from-a-genotype-phenotype-study
#17
Gabriele Quintavalle, Federica Riccardi, Gianna Franca Rivolta, Davide Martorana, Caterina Di Perna, Antonio Percesepe, Annarita Tagliaferri
Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores...
April 27, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28447099/endogenous-developmental-endothelial-locus-1-limits-ischaemia-related-angiogenesis-by-blocking-inflammation
#18
Anne Klotzsche-von Ameln, Sebastian Cremer, Jedrzej Hoffmann, Peggy Schuster, Sherif Khedr, Irina Korovina, Maria Troullinaki, Ales Neuwirth, David Sprott, Antonios Chatzigeorgiou, Matina Economopoulou, Alessia Orlandi, Andreas Hain, Andreas M Zeiher, Andreas Deussen, George Hajishengallis, Stefanie Dimmeler, Triantafyllos Chavakis, Emmanouil Chavakis
We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin-dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischaemia-related angiogenesis. Intriguingly, Del-1-deficient mice displayed increased neovascularisation in two independent ischaemic models (retinopathy of prematurity and hind-limb ischaemia), as compared to Del-1-proficient mice...
April 27, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28424821/noacs-for-treatment-of-venous-thromboembolism-in-clinical-practice
#19
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
#20
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
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