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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
#1
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/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
#2
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/28507519/vasorelaxing-action-of-the-kynurenine-metabolite-xanthurenic-acid-the-missing-link-in-endotoxin-induced-hypotension
#3
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/28493056/non-vitamin-k-oral-anticoagulants-for-stroke-prevention-in-special-populations-with-atrial-fibrillation
#4
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/28479844/american-college-of-cardiology
#5
Walter Alexander
We report on selected research presented at the ACC 66th Annual Scientific Session and Expo, including sessions on proprotein convertase subtilisin/kexin type 9 inhibitors, anti-Xa anticoagulants, and a direct thrombin inhibitor.
May 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28476405/international-normalized-ratio-is-significantly-elevated-with-rivaroxaban-and-apixaban-drug-therapies-a-retrospective-study
#6
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/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#7
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
#8
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-vs-enoxaparin-for-prevention-of-venous-thromboembolism-following-orthopedic-surgery-a-dose-response-meta-analysis
#9
R A Boyd, L DiCarlo, J 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 q.d.) 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 vs...
May 3, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28447415/the-danger-of-relying-on-the-aptt-and-pt-in-patients-on-doac-therapy-a-potential-patient-safety-issue
#10
REVIEW
D M Adcock, R C Gosselin
Prolongation of the activated partial thromboplastin time (APTT) and prothrombin time/international normalized ratio (PT/INR) correlates poorly with plasma concentrations of direct oral anticoagulant agents (DOACS) including direct thrombin and direct Xa inhibitors. It has been repeatedly demonstrated that patients can have normal APTT and PT/INR with a therapeutic plasma concentration of a DOAC. Clinicians can no longer rely on a normal APTT and PT to determine that an anticoagulated patient is safe to undergo an invasive procedure...
May 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28446469/anticoagulation-for-mechanical-heart-valves-will-oral-factor-xa-inhibitors-be-effective
#11
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
#12
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
https://www.readbyqxmd.com/read/28439967/involvement-of-heparanase-procoagulant-domain-in-bleeding-and-wound-healing
#13
Yonatan Crispel, Shourouk Ghanem, Judith Attias, Inna Kogan, Benjamin Brenner, Yona Nadir
BACKGROUND: Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase and attenuated inflammation, tumor growth and vascularization. AIMS: The present study aimed to identify the procoagulant domain in the heparanase molecule and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis...
April 25, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28439702/a-comparison-of-apixaban-and-dabigatran-etexilate-for-thromboprophylaxis-following-hip-and-knee-replacement-surgery
#14
Adriane Mayer, Philipp Schuster, Bernd Fink
INTRODUCTION: Patients who have undergone hip or knee replacement surgery are exposed to a high risk of developing a post-operative venous thromboembolus and so have a need for an effective, medication-based, thrombosis prophylaxis. New orally active anticoagulants have been available for a few years now. These specific substances directly block either thrombin (e.g., dabigatran etexilate) or Factor Xa (e.g., apixaban). It is not clear whether there are any efficacy differences between these two substances because there have never been any head-to-head studies carried out...
April 24, 2017: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/28429198/managing-the-perioperative-patient-on-direct-oral-anticoagulants
#15
Jordan Leitch, Janet van Vlymen
PURPOSE: Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery...
June 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28427335/cholesterol-esterification-in-plasma-as-a-biomarker-for-liver-function-and-prediction-of-mortality
#16
Thorsten Kaiser, Benedict Kinny-Köster, Michael Bartels, Thomas Berg, Markus Scholz, Cornelius Engelmann, Daniel Seehofer, Susen Becker, Uta Ceglarek, Joachim Thiery
BACKGROUND: Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value. Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs...
April 20, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28421343/antiplatelets-and-anticoagulants-in-vitreoretinal-surgery-with-a-special-emphasis-on-novel-anticoagulants-a-national-survey-and-review
#17
REVIEW
Rupa Patel, Stephen Charles, Assad Jalil
PURPOSE: To survey current practice and opinion regarding the cessation of antiplatelet and anticoagulant agents prior to vitreoretinal surgery, with special emphasis on novel anticoagulants, and to provide an overview of current literature. METHODS: An online survey was sent to 167 members of the British and Eire Association of Vitreoretinal Surgeons (BEAVRS). A literature search and analysis was conducted on studies that reviewed the bleeding risk of antiplatelet and anticoagulant agents...
April 18, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28420729/factor-v-anticoagulant-cofactor-activity-that-targets-the-early-phase-of-coagulation
#18
Salvatore Santamaria, Natalia Reglińska-Matveyev, Magdalena Gierula, Rodney M Camire, James T B Crawley, David A Lane, Josefin Ahnström
Tissue factor pathway inhibitor (TFPI), the main inhibitor of initiation of coagulation, exerts an important anticoagulant role through the factor Xa (FXa)-dependent inhibition of tissue factor/factor VIIa (FVIIa). Protein S is a TFPI cofactor, enhancing the efficiency of FXa inhibition. TFPI can also inhibit prothrombinase assembly by directly interacting with coagulation factor V (FV) which has been activated by FXa. Since full-length TFPI associates with FV in plasma, we hypothesized that FV may influence TFPI inhibitory function...
April 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28415603/synthesis-and-evaluation-of-anthranilamide-based-derivatives-as-fxa-inhibitors
#19
Changjiang Huang, Wenzhi Wang, Yao Li, Shijun Zhang, Fancui Meng, Weiren Xu, Jing Yuan, Ligong Chen
Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors aiming to ameliorate the toxicity of traditional FXa inhibitors in clinic. The data indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable FXa inhibitory activity and excellent selectivity over thrombin in vitro...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412907/review-of-the-pharmacology-of-the-emerging-possibilities-of-the-direct-oral-anticoagulants-reversal
#20
Matej Samos, Lucia Stanciakova, Ingrid Skornova, Tomas Bolek, Frantisek Kovar, Jan Stasko, Peter Galajda, Marian Mokan, Peter Kubisz
BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with non-valvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients...
April 13, 2017: Current Drug Metabolism
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