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https://www.readbyqxmd.com/read/28535438/determination-of-edoxaban-equivalent-concentrations-in-human-plasma-by-an-automated-anti-factor-xa-chromogenic-assay
#1
Ling He, Jarema Kochan, Min Lin, Alexander Vandell, Karen Brown, Francois Depasse
INTRODUCTION: This phase I, open-label, multiple-dose, two-treatment study assessed the relationship between edoxaban equivalent concentration derived from an anti-FXa assay with the summed concentration of edoxaban and its active metabolite, M-4, as assessed by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This study also assessed the relationship between edoxaban plasma concentrations assessed by LC/MS/MS in sodium citrate and lithium heparin tubes. MATERIALS AND METHODS: Healthy volunteers were randomized to receive once-daily edoxaban 60mg or 90mg for 5days (15 participants per treatment group)...
May 7, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28525532/the-effects-of-indirect-and-direct-acting-anticoagulants-on-lupus-anticoagulant-assays-a-large-retrospective-study-at-a-coagulation-reference-laboratory
#2
Jansen N Seheult, Michael P Meyer, Franklin A Bontempo, Irina Chibisov
Objectives: To investigate the effects of indirect- and direct-acting anticoagulants on the interpretation of lupus anticoagulant (LAC) assays. Methods: A retrospective database review was performed to identify all LAC panels from November 2012 to November 2015. The positivity rates for three LAC tests were compared among various anticoagulant medications. Results: This analysis included 7,721 LAC panels. Direct oral anticoagulants, warfarin, and unfractionated heparin (UFH) were associated with higher LAC positivity rates compared with patients not receiving documented anticoagulation (83% for argatroban, 58% for dabigatran, 72% for rivaroxaban, 53% for apixaban, 56% for warfarin, and 36% for UFH vs 29% for no anticoagulation, P < ...
May 19, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28522347/functional-analysis-of-tcctlp-5c2-a-chymotrypsin-like-serine-protease-needed-for-molting-in-tribolium-castaneum
#3
Daniel Albaum, Gunnar Broehan, Subbaratnam Muthukrishnan, Hans Merzendorfer
In a previous study, we have characterized a gene family encoding chymotrypsin-like proteases from the red flour beetle, Tribolium castaneum (TcCTLPs). We identified 14 TcCTLP genes that were predominantly expressed in the midgut, where they presumably function in digestion. Two genes (TcCTLP-6C and TcCTLP-5C2), however, additionally showed considerable expression in the carcass, and RNAi studies demonstrated that they are required for molting (Broehan et al., 2010; Insect Biochem. Mol. Biol 40, 274-83). Thus, the enzyme has distinct functions in different physiological environments...
May 15, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28512699/an-open-label-crossover-study-of-the-pharmacokinetics-of-the-60-mg-edoxaban-tablet-crushed-and-administered-either-by-a-nasogastric-tube-or-in-apple-puree-in-healthy-adults
#4
Kenneth Duchin, Anil Duggal, George J Atiee, Motonori Kidokoro, Tadanobu Takatani, Nicole Lazarus Shipitofsky, Ling He, George Zhang, Tarundeep Kakkar
BACKGROUND: Edoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism. OBJECTIVES: This study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water suspension or orally mixed in apple puree. METHODS: This phase 1, open-label, crossover study randomized 30 healthy adults to receive three edoxaban treatment regimens (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered via a nasogastric tube or orally in apple puree) in one of six treatment sequences...
May 17, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28510738/pharmacokinetic-pharmacodynamic-model-for-unfractionated-heparin-dosing-during-cardiopulmonary-bypass
#5
X Delavenne, E Ollier, S Chollet, F Sandri, J Lanoiselée, S Hodin, A Montmartin, J-F Fuzellier, P Mismetti, L Gergelé
Background: High-dose heparin is used during cardiopulmonary bypass (CPB) to prevent thrombosis in the circuits used for extracorporeal circulation. The aim of this study was, initially, to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD parameters and their correlation with the results of the routine haemostatic test activated clotting time (ACT) and thereafter to develop a Bayesian estimator enabling an individualized dosing strategy...
May 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28507519/vasorelaxing-action-of-the-kynurenine-metabolite-xanthurenic-acid-the-missing-link-in-endotoxin-induced-hypotension
#6
Francesco Fazio, Albino Carrizzo, Luana Lionetto, Antonio Damato, Luca Capocci, Mariateresa Ambrosio, Giuseppe Battaglia, Valeria Bruno, Michele Madonna, Maurizio Simmaco, Ferdinando Nicoletti, Carmine Vecchione
The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28506952/retrospective-evaluation-of-pregnant-women-with-celiac-disease
#7
Kemal Beksaç, Gökçen Örgül, Murat Çağan, Ergun Karaağaoğlu, Serap Arslan, Mehmet Sinan Beksaç
OBJECTIVE: To show celiac disease (CD) and its poor pregnancy outcome relationship, and to demonstrate the importance of a gluten-free diet together with low-dose low-molecular-weight heparin (LMWH) and low-dose corticosteroid (LDC) in the management of pregnancies with CD. MATERIAL AND METHODS: This study consisted of 2 groups of patients. Six patients with CD (control group) on a gluten-free diet were monitored during their first pregnancies within the framework of antenatal care program and their pregnancy outcomes were compared with eight poorly-treated pregnant patients with CD (study group) who were referred from other medical institutions...
March 15, 2017: Journal of the Turkish German Gynecological Association
https://www.readbyqxmd.com/read/28501328/evaluation-of-venous-thrombosis-and-tissue-factor-in-epithelial-ovarian-cancer
#8
Joshua G Cohen, Emily Prendergast, Julia E Geddings, Ann E Walts, Hasmik Agadjanian, Yohei Hisada, Beth Y Karlan, Nigel Mackman, Christine S Walsh
OBJECTIVE: Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population. METHODS: We performed a case-control study of OCCC and HGSOC patients with and without VTE...
May 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28495674/noncentral-nervous-system-systemic-embolism-in-patients-with-atrial-fibrillation-results-from-rocket-af-rivaroxaban-once-daily-oral-direct-factor-xa-inhibition-compared-with-vitamin-k-antagonism-for-prevention-of-stroke-and-embolism-trial-in-atrial-fibrillation
#9
Ryan Orgel, Daniel Wojdyla, David Huberman, Jonathan L Halperin, Günter Breithardt, Daniel E Singer, Keith A A Fox, Graeme J Hankey, Kenneth W Mahaffey, W Schuyler Jones, Manesh R Patel
No abstract text is available yet for this article.
May 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28493056/non-vitamin-k-oral-anticoagulants-for-stroke-prevention-in-special-populations-with-atrial-fibrillation
#10
REVIEW
Arnaud Bisson, Denis Angoulvant, Raphael Philippart, Nicolas Clementy, Dominique Babuty, Laurent Fauchier
Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events...
May 10, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28486148/adaptive-release-of-heparin-from-anticoagulant-hydrogels-triggered-by-different-blood-coagulation-factors
#11
Manfred F Maitz, Jan Zitzmann, Jasmin Hanke, Claudia Renneberg, Mikhail V Tsurkan, Claudia Sperling, Uwe Freudenberg, Carsten Werner
Feedback-controlled anticoagulant hydrogels were formed by crosslinking the anticoagulant heparin with star-shaped poly(ethylene glycol) using peptide linkers, which are selectively cleaved by different activated blood coagulation factors acting as proteolytic enzymes. Various cleavable peptide units, differing either in their thrombin turnover rates or in their responsiveness to factors activated earlier in the course of blood coagulation, were used for the formation of the biohybrid materials. Release triggered by the early coagulation factors Xa (FXa) or FXIIa/kallikrein was shown to enhance the efficiency of the released anticoagulant...
April 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28477151/coagulation-testing-in-intracerebral-hemorrhage-related-to-non-vitamin-k-antagonist-oral-anticoagulants
#12
Jan C Purrucker, Timolaos Rizos, Kirsten Haas, Marcel Wolf, Shujah Khan, Peter U Heuschmann, Roland Veltkamp
BACKGROUND: Intracerebral hemorrhage (ICH) is a life-threatening complication of non-vitamin K antagonist oral anticoagulants (NOAC). Little is known about the effect of intensity of anticoagulation on NOAC-ICH. We describe the current use of coagulation testing in the emergency setting and explore associations with baseline size and expansion of hematoma as determined in a previous study. METHODS: Data from the prospective multicenter RASUNOA registry were analyzed...
May 5, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28476405/international-normalized-ratio-is-significantly-elevated-with-rivaroxaban-and-apixaban-drug-therapies-a-retrospective-study
#13
Fanny Ofek, Samuel Bar Chaim, Nirit Kronenfeld, Tomer Ziv-Baran, Matitiahu Berkovitch
PURPOSE: Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself...
May 2, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28474722/highly-selective-and-rapidly-activatable-fluorogenic-thrombin-sensors-and-application-in-human-lung-tissue
#14
Alicia Megia-Fernandez, Bethany Mills, Chesney Michels, Sunay V Chankeshwara, Kevin Dhaliwal, Mark Bradley
A library of FRET-based peptides were prepared and studied as Thrombin substrates. This identified probes that showed selective activation by Thrombin, low fluorescent background signals, stability to Factor Xa, matrix metalloproteases, and primary human inflammatory cell lysates and supernatant. These were selected for further optimization, creating a second generation of fluorogenic probes with improved solubility and Plasmin resistance. The optimised probe allowed the detection of Thrombin activity in ex vivo fibrotic human tissue...
May 23, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#15
Markus Honickel, Necib Akman, Oliver Grottke
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist (VKA) anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity)...
April 4, 2017: Shock
https://www.readbyqxmd.com/read/28469161/revisiting-antithrombotic-therapeutics-sculptin-a-novel-specific-competitive-reversible-scissile-and-tight-binding-inhibitor-of-thrombin
#16
Asif Iqbal, Mauricio Barbugiani Goldfeder, Rafael Marques-Porto, Huma Asif, Jean Gabriel de Souza, Fernanda Faria, Ana Marisa Chudzinski-Tavassi
Thrombin is a multifunctional enzyme with a key role in the coagulation cascade. Its functional modulation can culminate into normal blood coagulation or thrombosis. Thus, the identification of novel potent inhibitors of thrombin are of immense importance. Sculptin is the first specific thrombin inhibitor identified in the transcriptomics analysis of tick's salivary glands. It consists of 168 residues having four similar repeats and evolutionary diverged from hirudin. Sculptin is a competitive, specific and reversible inhibitor of thrombin with a Ki of 18...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467656/direct-oral-anticoagulants-versus-enoxaparin-for-prevention-of-venous-thromboembolism-following-orthopedic-surgery-a-dose-response-meta-analysis
#17
Rebecca A Boyd, Lorenzo DiCarlo, Jaap W Mandema
We carried out a dose-response model-based meta-analysis to assess venous thromboembolism (VTE) and bleeding with factor Xa (FXa) inhibitors (apixaban, edoxaban, rivaroxaban) and a thrombin inhibitor (dabigatran) compared with European (EU) (40 mg QD) and North American (NA) (30 mg Q12H) dose regimens of a low molecular weight heparin (enoxaparin) following orthopedic surgery. Statistically significant differences in both VTE and bleeding outcomes were found between the NA and EU doses of enoxaparin, with odds ratios [95% confidence interval] for the NA versus EU dose of 0...
May 3, 2017: Clinical and Translational Science
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
#18
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/28446469/anticoagulation-for-mechanical-heart-valves-will-oral-factor-xa-inhibitors-be-effective
#19
EDITORIAL
Noel C Chan, Jeffrey I Weitz, John W Eikelboom
No abstract text is available yet for this article.
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28441767/inhibitory-effect-of-triterpenoids-from-panax-ginseng-on-coagulation-factor-x
#20
Lingxin Xiong, Zeng Qi, Bingzhen Zheng, Zhuo Li, Fang Wang, Jinping Liu, Pingya Li
Enzymes involved in the coagulation process have received great attention as potential targets for the development of oral anti-coagulants. Among these enzymes, coagulation factor Xa (FXa) has remained the center of attention in the last decade. In this study, 16 ginsenosides and two sapogenins were isolated, identified and quantified. To determine the inhibitory potential on FXa, the chromogenic substrates method was used. The assay suggested that compounds 5, 13 and 18 were mainly responsible for the anti-coagulant effect...
April 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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