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https://www.readbyqxmd.com/read/28634095/comparative-effectiveness-and-safety-of-drug-prophylaxis-for-prevention-of-venous-thromboembolism-after-total-knee-arthroplasty
#1
Guy Cafri, Elizabeth W Paxton, Yuexin Chen, Craig T Cheetham, Michael K Gould, Janet Sluggett, Stefano A Bini, Monti Khatod
BACKGROUND: Rates of venous thromboembolism in contemporary studies of primary total knee arthroplasty (TKA) have been reported to be as high as 3.5%. Although drug prophylaxis is effective, the best option among these regimens is not well established. The purpose of this study was to evaluate the comparative effectiveness and safety of aspirin, low-molecular-weight heparin, synthetic pentasaccharide factor Xa inhibitors, and vitamin K antagonist. METHODS: Data were from a US total joint replacement registry, with 30,499 patients receiving unilateral TKA from May 16, 2006, to December 31, 2013...
May 31, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28615214/safety-and-efficacy-of-rivaroxaban-in-patients-with-cardiac-implantable-electronic-devices-observations-from-the-rocket-af-trial
#2
George C Leef, Anne S Hellkamp, Manesh R Patel, Richard C Becker, Scott D Berkowitz, Günter Breithardt, Jonathan L Halperin, Graeme J Hankey, Werner Hacke, Christopher C Nessel, Daniel E Singer, Keith A A Fox, Kenneth W Mahaffey, Jonathan P Piccini
BACKGROUND: Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. METHODS AND RESULTS: Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision...
June 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28604566/novel-oral-anticoagulants-in-the-peri-endoscopic-period
#3
Michael Genualdi, William H Frishman
Millions of patients in the United States are currently prescribed some form of anticoagulation therapy. Recently, novel oral anticoagulants (NOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, have begun to replace warfarin as the drugs of choice for anticoagulation. As the use of these medications becomes more widespread, it is increasingly important for gastroenterologists to understand the risks associated with performing endoscopic procedures on patients who are taking NOACs. In this review, we provide an overview of the NOACs, as well as current guidelines from international societies regarding the management of patients scheduled to undergo endoscopic procedures who are prescribed these medications...
April 6, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28604464/liver-transplantation-in-a-patient-with-antiphospholipid-syndrome-a-case-report
#4
Rachel C Steckelberg, Zarah D Antongiorgi, Randolph H Steadman
Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder characterized by autoantibodies to cell membrane phospholipids. While altered coagulation can complicate end-stage liver disease, there are few reports describing the perioperative management for liver transplantation in recipients with a preexisting hypercoagulable disorder, such as APS. We present a patient with a history of APS, Budd-Chiari syndrome with cirrhosis, hepatopulmonary syndrome, and heparin-induced thrombocytopenia who underwent liver transplantation complicated by hepatic artery thrombosis...
June 8, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28595862/safety-and-efficacy-of-uninterrupted-apixaban-therapy-versus-warfarin-during-atrial-fibrillation-ablation
#5
Ruchit R Shah, Ajay Pillai, Pascha Schafer, David Meggo, Tom McElderry, Vance Plumb, Takumi Yamada, Vineet Kumar, Harish Doppalapudi, Alicia Gunter, Emily Pentecost, William R Maddox
Thromboembolic cerebrovascular accident remains a rare but potentially devastating complication of catheter-based atrial fibrillation (AF) ablation. Uninterrupted oral anticoagulant therapy with warfarin has become the standard of care when performing catheter-based AF ablation. Compared with warfarin, apixaban, a factor Xa inhibitor, has been shown to reduce the risk of stroke and major bleeding in nonvalvular AF. With an increase in apixaban use for stroke prophylaxis in patients with AF, there is an increased interest in the safety and efficacy of uninterrupted apixaban therapy during AF ablation...
May 10, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#6
Truman J Milling, Jennifer Frontera
Thrombosis is a leading cause of morbidity and mortality in the United States. Arterial and venous thromboses are implicated in the pathogenesis of major disorders, including myocardial infarction, ischemic stroke, and venous thromboembolism. Over the past decade, direct oral anticoagulants (DOACs) (eg, direct thrombin inhibitor and factor Xa [FXa] inhibitors) have been adopted as alternatives to warfarin due to their clinical advantages and efficacy for the treatment of thrombosis. As with all anticoagulants, treatment with DOACs is associated with a risk of major bleeding, including life-threatening gastrointestinal bleeds and intracranial hemorrhages (ICHs)...
April 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28577290/in-silico-discovery-of-novel-fxa-inhibitors-by-pharmacophore-modeling-and-molecular-docking
#7
Yinglan Pu, Hui Liu, Yeheng Zhou, Jiale Peng, Yaping Li, Penghua Li, Yingying Li, Xingyong Liu, Li Zhang
Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules). The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa, and 10 novel structural compounds were discovered as potent candidate molecules...
June 2, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28569922/thrombin-is-a-selective-inducer-of-heparanase-release-from-platelets-and-granulocytes-via-protease-activated-receptor-1
#8
Mifleh Tatour, Ma'anit Shapira, Elena Axelman, Shourouk Ghanem, Anat Keren-Politansky, Lilach Bonstein, Benjamin Brenner, Yona Nadir
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. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells. Platelets and granulocytes were purified from pooled normal plasma and were incubated with ATP, ADP, epinephrine, collagen, ristocetin, arachidonic acid, serotonin, LPS and thrombin...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569372/venous-thromboembolism-prophylaxis-after-tka-aspirin-warfarin-enoxaparin-or-factor-xa-inhibitors
#9
Abiram Bala, James I Huddleston, Stuart B Goodman, William J Maloney, Derek F Amanatullah
BACKGROUND: There is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors. QUESTIONS/PURPOSES: Using a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time? METHODS: We queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes...
May 31, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28569297/direct-n-acylation-of-sulfoximines-with-carboxylic-acids-catalyzed-by-the-b3no2-heterocycle
#10
Hidetoshi Noda, Yasuko Asada, Masakatsu Shibasaki, Naoya Kumagai
In contrast to recent significant progress in the development of catalytic methodologies for nitrogen acylations, syntheses of N-acyl sulfoximines have been slow to evolve, and still largely rely on the use of stoichiometric amounts of activating reagents. Here we describe the direct acylation of the nitrogen atom in sulfoximines with carboxylic acids promoted by a heterocyclic catalyst featuring the B3NO2 ring system. The protocol used was found to be operationally simple and to tolerate a wide range of functional groups, furnishing the N-acylated sulfoximines in good yield...
June 1, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28565907/thermodynamic-characterization-of-hydration-sites-from-integral-equation-derived-free-energy-densities-application-to-protein-binding-sites-and-ligand-series
#11
Stefan Güssregen, Hans Matter, Gerhard Hessler, Evanthia Lionta, Jochen Heil, Stefan M Kast
Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design...
June 16, 2017: Journal of Chemical Information and Modeling
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
#12
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 < ...
June 1, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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