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Journal of Thrombosis and Haemostasis: JTH

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https://www.readbyqxmd.com/read/28092428/reproducibility-of-clinical-events-adjudications-in-a-trial-of-venous-thromboembolism-prevention
#1
P Girard, A Penaloza, F Parent, B Gable, O Sanchez, P Durieux, P Hausfater, S Dambrine, G Meyer, P-M Roy
BACKGROUND: When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CEC) is recommended to homogenize the interpretation of investigators data. However, the reproducibility of CEC adjudications is almost unexplored. OBJECTIVES: To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. METHODS: The PREVENU study, a multicenter trial of VTE prevention, included 15,351 hospitalized medical patients...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28092426/incomplete-reversibility-of-platelet-inhibition-following-prolonged-exposure-to-ticagrelor
#2
A J Gerrits, J A Jakubowski, A Sugidachi, A D Michelson, A L Frelinger
INTRODUCTION: Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). METHODS: Whole blood was treated in vitro with ~50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28092405/thrombin-contributes-to-protective-immunity-in-pneumonia-derived-sepsis-via-fibrin-polymerization-and-platelet-neutrophil-interactions
#3
Theodora A M Claushuis, Sacha F de Stoppelaar, Ingrid Stroo, Joris J T H Roelofs, Roelof Ottenhoff, Tom van der Poll, Cornelis van 't Veer
BACKGROUND: Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental for outcome due to microvascular failure but can also enhance host defense. The role of thrombin herein has not been fully elucidated. OBJECTIVE: We aimed to investigate the contribution of thrombin to the host response during pneumonia derived sepsis. METHODS: Mice treated with the specific thrombin inhibitor Dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28090741/conformational-quiescence-of-adamts13-prevents-proteolytic-promiscuity-reply
#4
K South, M O Freitas, D A Lane
We thank Drs Cao and Long Zheng for their interest in our paper recently published in JTH [1] in which we reported our findings that C-terminally truncated variants of ADAMTS13 directly cleave the Aα chain of fibrinogen. We postulated that conformationally activated ADAMTS13 [2, 3]may be able to cleave substrate(s) in addition to its usual substrate, the A2 domain of von Willebrand factor (VWF). In their letter, Cao and Long Zheng report that rather than cleaving fibrinogen directly, ADAMTS13 variants act indirectly, activating plasminogen, a common contaminant in commercial fibrinogen preparations...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079982/recombinant-soluble-apyrase-apt102-inhibits-thrombosis-and-intimal-hyperplasia-in-vein-grafts-without-adversely-affecting-hemostasis-or-re-endothelialization
#5
Y Ji, O Adeola, T L Strawn, S S Jeong, R Chen, W P Fay
BACKGROUND: Occlusion of vein grafts (VGs) after bypass surgery due to thrombosis and intimal hyperplasia (IH) is a major clinical problem. Apyrases are enzymes that scavenge extracellular ATP and ADP and promote adenosine formation at sites of vascular injury and hence have potential to inhibit vein graft pathology. OBJECTIVES: We examined the effects of recombinant soluble human apyrase, APT102, on platelets, smooth muscle cells (SMCs), and endothelial cells (ECs) in vitro and thrombosis and IH in murine VGs...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079978/targeting-coagulation-factor-receptors-protease-activated-receptors-in-idiopathic-pulmonary-fibrosis
#6
REVIEW
Cong Lin, Keren Borensztajn, C Arnold Spek
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate above 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease but do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF identified several possible targets for therapeutic interventions...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#7
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28078756/infections-in-non-splenectomized-persistent-or-chronic-primary-immune-thrombocytopenia-adults-risk-factors-and-vaccination-effect
#8
Guillaume Moulis, Maryse Lapeyre-Mestre, Aurore Palmaro, Laurent Sailler
INTRODUCTION: Risk factors for infection and protective effect of vaccines in immune thrombocytopenia (ITP) patients in the era of rituximab therapy are unknown. OBJECTIVES: To assess the risk factors for serious and non-serious infections (respectively, SIs and NSIs) in non-splenectomized adults treated for persistent or chronic primary ITP, including the effect of pneumococcal and influenza vaccines. PATIENTS/METHODS: The population was the 2009-2012 FAITH cohort (n=1805), which is the cohort of all incident (newly diagnosed) primary ITP adults treated >3months in France built in the national health insurance database (SNIIRAM)...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28075532/clinical-and-biochemical-characterization-of-the-prothrombin-belgrade-mutation-in-a-large-serbian-pedigree-new-insights-into-antithrombin-resistance-mechanism
#9
Predrag Miljic, Maja Gvozdenov, Yuki Takagi, Akira Takagi, Iva Pruner, Marija Dragojevic, Branko Tomic, Jelena Bodrozic, Tetsuhito Kojima, Dragica Radojkovic, Valentina Djordjevic
BACKGROUND: The recently reported c.1787G>A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. OBJECTIVES: We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation...
January 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28075530/dysregulation-of-pldn-pallidin-is-a-mechanism-for-platelet-dense-granule-deficiency-in-runx1-haplodeficiency
#10
G F Mao, L E Goldfinger, D C Fan, M P Lambert, G Jalagadugula, R Freishtat, A K Rao
BACKGROUND: Inherited RUNX1 haplodeficiency is associated with thrombocytopenia and platelet dysfunction. Dense granule (DG) deficiency is reported in patients with RUNX1 haplodeficiency, but the molecular mechanisms are unknown. Platelet mRNA expression profiling in a patient previously reported by us with a RUNX1 mutation and platelet dysfunction showed decreased expression of PLDN (BLOC1S6), which encodes for pallidin, a subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) involved in granule biogenesis...
January 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28071872/mutant-botrocetin-2-inhibits-von-willebrand-factor-induced-platelet-agglutination
#11
T Matsui, A Hori, J Hamako, F Matsushita, Y Ozeki, Y Sakurai, M Hayakawa, M Matsumoto, Y Fujimura
BACKGROUND: Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and β subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. OBJECTIVES: We exploited Bot2's VWF-binding capacity to try and create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. METHODS AND RESULTS: Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (rBot2) was purified on an anti-botrocetin column...
January 10, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28064465/what-the-neighbors-say
#12
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
January 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28064443/glittering-prizes
#13
EDITORIAL
F R Rosendaal, P H Reitsma
No abstract text is available yet for this article.
January 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28063245/dosing-algorithms-for-vitamin-k-antagonists-across-vkorc1-and-cyp2c9-genotypes
#14
Ekaterina V Baranova, Talitha I Verhoef, Georgia Ragia, Saskia Le Cessie, Folkert W Asselbergs, Anthonius de Boer, Vangelis G Manolopoulos, Anke H Maitland-van der Zee
BACKGROUND: The multicenter, single-blind, randomized EU-PACT trial compared safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep venous thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. OBJECTIVES: To explore possible reasons for the lack of differences between trial arms this secondary analysis of EU-PACT data evaluated the performance of both dosing algorithms across VKORC1-CYP2C9 genetic sub-groups...
January 7, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28058824/the-effect-of-amiodarone-on-warfarin-anticoagulation-a-register-based-nationwide-cohort-study-involving-the-swedish-population
#15
Johan Holm, Jonatan D Lindh, Marine L Andersson, Buster Mannheimer
BACKGROUND: Data indicate that the interaction between warfarin and amiodarone results in increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as comedication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. OBJECTIVES: An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nation-wide registries...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28058806/clustering-of-gpvi-dimers-upon-adhesion-to-collagen-as-a-mechanism-to-regulate-gpvi-signalling-in-platelets
#16
N S Poulter, A Y Pollitt, D M Owen, E E Gardiner, R K Andrews, H Shimizu, D Ishikawa, D Bihan, R W Farndale, M Moroi, S P Watson, S M Jung
BACKGROUND: Platelet GPVI binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen and occurs constitutively on resting platelets. OBJECTIVE: To identify higher order oligomerisation (clustering) of pre-existing GPVI-dimers upon interaction with collagen as a mechanism to initiate GPVI-mediated signalling. METHODS: GPVI was located using fluorophore-conjugated GPVI-dimer-specific Fab (antigen-binding fragment)...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28058802/increased-thrombin-generation-in-a-mouse-model-of-cancer-cachexia-is-partially-interleukin-6-dependent
#17
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/28055147/monitoring-of-treatment-with-vitamin-k-antagonists-recombinant-thromboplastins-are-more-sensitive-to-factor-vii-than-tissue-extract-thromboplastins
#18
Joseph S Biedermann, Antonius M H P van den Besselaar, Moniek P M de Maat, Frank W G Leebeek, Marieke J H A Kruip
BACKGROUND: Differences regarding sensitivity to factor VII (FVII) have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but evidence is scarce. Differences in FVII sensitivity are clinically relevant since they can affect INR stability during treatment with vitamin K antagonists (VKA). OBJECTIVES: To determine if commercial thromboplastins react differently to changes in FVII. METHODS: We studied the effect of addition of FVII on the INR in plasma using three tissue-extract (Neoplastin C1+, Hepato Quick, Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, Coaguchek XS) thromboplastins...
January 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28055145/conformational-quiescence-of-adamts13-prevents-proteolytic-promiscuity-comment
#19
W J Cao, X L Zheng
Von Willebrand factor (VWF) is the only substrate identified for ADAMTS13 to date [1]. How ADAMTS13 achieves such remarkable substrate specificity remains a mystery. Previous studies demonstrated that carboxyl-terminal domains including 2-8(th) thrombospondin type 1 repeat (TSP1) and CUB domains are dispensable for cleavage of VWF substrate under various conditions [2, 3]. However, these carboxyl-terminal domains were later found to exhibit a disulfide bond reducing activity [4] and to interact with globular VWF via its D4 domain [5]...
January 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28054748/peter-andreasen-31-december-1947-15-november-2016
#20
(no author information available yet)
No abstract text is available yet for this article.
January 5, 2017: Journal of Thrombosis and Haemostasis: JTH
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