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https://www.readbyqxmd.com/read/28650000/andexanet-alfa-a-recombinant-mimetic-of-human-factor-xa-for-the-reversal-of-anticoagulant-therapies
#1
G Escolar, M Diaz-Ricart, E Arellano-Rodrigo
Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28648320/cost-effectiveness-of-edoxaban-vs-warfarin-in-patients-with-atrial-fibrillation-based-on-results-of-the-engage-af-timi-48-trial-taiwanese-perspective
#2
Katherine A Vilain, Ming Chin Yang, Elise Chia Hui Tan, Kaijun Wang, Haiyan Li, Wan Hsuan Hsu, Robert P Giugliano, David J Cohen, Elizabeth A Magnuson
BACKGROUND: Novel anticoagulants, such as factor Xa inhibitors, have entered clinical practice as alternatives to warfarin for the prevention of stroke and systemic embolic event (SEE) in patients with atrial fibrillation (AF). It is not known whether edoxaban, the fourth-to-market factor Xa inhibitor approved for this indication, will be cost-effective in Taiwan, where the cost of warfarin monitoring is prohibitive. METHODS: A Markov model projecting lifetime results of edoxaban 60 mg/30 mg dose-reduced versus warfarin in patients with nonvalvular AF, based on the ENGAGE AF - TIMI 48 trial, found edoxaban to be of high value relative to warfarin, from the perspective of the US health care system...
May 2017: Value in Health Regional Issues
https://www.readbyqxmd.com/read/28645996/treatment-of-suspected-pulmonary-embolism-in-a-morbidly-obese-patient
#3
Viviene Heitlage, Mary Beth Borgstadt, Lisa Carlson
PURPOSE: A case highlighting challenges with enoxaparin dosage and monitoring in obese patients is presented. SUMMARY: A morbidly obese 22-year-old Caucasian female (height, 168 cm; weight, 322 kg; body mass index [BMI], 114 kg/m(2)) who presented to the emergency department with acute-onset dyspnea and hypoxia was empirically initiated on enoxaparin for suspected pulmonary embolism at the institution's standard maximum dosage (160 mg subcutaneously every 12 hours)...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28645473/efficacy-and-safety-of-rivaroxaban-versus-warfarin-in-patients-taking-nondihydropyridine-calcium-channel-blockers-for-atrial-fibrillation-from-the-rocket-af-trial
#4
Jeffrey B Washam, Anne S Hellkamp, Yuliya Lokhnygina, Jonathan P Piccini, Scott D Berkowitz, Christopher C Nessel, Richard C Becker, Günter Breithardt, Keith A A Fox, Jonathan L Halperin, Graeme J Hankey, Kenneth W Mahaffey, Daniel E Singer, Manesh R Patel
Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in 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)...
May 29, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28643538/do-methodological-differences-account-for-the-current-controversy-on-tissue-factor-expression-in-platelets
#5
Marta Brambilla, Laura Rossetti, Chiara Zara, Paola Canzano, Peter L A Giesen, Elena Tremoli, Marina Camera
Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets...
June 23, 2017: Platelets
https://www.readbyqxmd.com/read/28639463/adverse-drug-reactions-and-cutaneous-manifestations-associated-with-anticoagulation
#6
Trang T Vu, Melinda Gooderham
Anticoagulants are amongst the most commonly prescribed medications worldwide. Although rare, localised and systemic drug reactions have been reported with anticoagulants that can lead to significant morbidity and mortality. Some of the first signs of drug reactions to anticoagulants are cutaneous changes that, when recognised early, can prevent significant complications. Dermatologists should be aware of these changes to make an early and accurate diagnosis. This is particularly important in instances of skin-induced necrosis caused by systemic toxicity to anticoagulants...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28634095/comparative-effectiveness-and-safety-of-drug-prophylaxis-for-prevention-of-venous-thromboembolism-after-total-knee-arthroplasty
#7
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/28625215/assessing-coagulation-by-rotational-thromboelastometry-rotem-in-rivaroxaban-anticoagulated-blood-using-hemostatic-agents
#8
Jonathan Bar, Alexa David, Tarek Khader, Mary Mulcare, Christopher Tedeschi
Introduction The use of direct oral anticoagulants (DOACs) such as rivaroxaban (Xarelto) is increasingly common. However, therapies for reversing anticoagulation in the event of hemorrhage are limited. This study investigates the ability of hemostatic agents to improve the coagulation of rivaroxaban-anticoagulated blood, as measured by rotational thromboelastometry (ROTEM). Hypothesis/Problem If a chitosan-based hemostatic agent (Celox), which works independently of the clotting cascade, is applied to rivaroxaban-anticoagulated blood, it should improve coagulation by decreasing clotting time (CT), decreasing clot formation time (CFT), and increasing maximum clot firmness (MCF)...
June 19, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28615214/safety-and-efficacy-of-rivaroxaban-in-patients-with-cardiac-implantable-electronic-devices-observations-from-the-rocket-af-trial
#9
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/28605123/in-vitro-effects-of-dalteparin-on-thrombin-generation-in-canine-plasma
#10
Carolyn Gara-Boivin, Jérôme R E Del Castillo, Marilyn E Dunn, Christian Bédard
BACKGROUND: The calibrated automated thrombogram (CAT) is a functional thrombin generation (TG) assay that may provide a new approach for monitoring anticoagulant therapy in dogs. The effects of dalteparin on TG variables in dogs are unknown. OBJECTIVES: Objectives were to establish normal TG variable ranges in dogs and measure the in vitro TG variables in canine pooled platelet-poor plasma (PPP) spiked with different dalteparin concentrations. METHODS: In the first experiment, plasma samples from 25 adult healthy Beagle dogs and 11 client-owned healthy dogs of multiple breeds was measured individually for obtaining normal TG values...
June 12, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28604566/novel-oral-anticoagulants-in-the-peri-endoscopic-period
#11
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
#12
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/28600979/circulating-microvesicle-number-function-and-small-rna-content-vary-with-age-gender-smoking-status-lipid-and-hormone-profiles
#13
Anoop K Enjeti, Anita Ariyarajah, Angel D'Crus, Michael Seldon, Lisa F Lincz
BACKGROUND: Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. OBJECTIVES: We evaluated the influence of age, gender, smoking status, lipid and hormone profiles on circulating MV in healthy subjects. METHODS: Platelet free plasma from 143 volunteer blood donors (males=80, females=63) was evaluated by standardized flow cytometry for MV expressing CD41 (platelet-derived), CD105 (endothelial-derived), CD235 (red cell-derived), TF (tissue factor) and phosphatidylserine (PS) MV...
April 20, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28595862/safety-and-efficacy-of-uninterrupted-apixaban-therapy-versus-warfarin-during-atrial-fibrillation-ablation
#14
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/28594049/venous-thromboembolism-past-present-and-future
#15
Sam Schulman, Walter Ageno, Stavros V Konstantinides
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, is associated with a considerable disease burden which continues to grow along with the longer life expectancy of the population worldwide. In the past century, parenteral heparin prophylaxis was established for hospitalised patients at elevated risk of VTE. More recently, non-vitamin K antagonist oral anticoagulants (NOACs) with a direct inhibiting effect on factor Xa or thrombin, underwent extensive testing in clinical trials and have been approved for patients undergoing hip or knee replacement...
June 8, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28589041/attenuated-late-phase-arc-transcription-in-the-dentate-gyrus-of-mice-lacking-egr3
#16
Amanda Maple, Rachel E Lackie, Diana I Elizalde, Stephanie L Grella, Chelsey C Damphousse, Collin Xa, Amelia L Gallitano, Diano F Marrone
The dentate gyrus (DG) engages in sustained Arc transcription for at least 8 hours following behavioral induction, and this time course may be functionally coupled to the unique role of the DG in hippocampus-dependent learning and memory. The factors that regulate long-term DG Arc expression, however, remain poorly understood. Animals lacking Egr3 show less Arc expression following convulsive stimulation, but the effect of Egr3 ablation on behaviorally induced Arc remains unknown. To address this, Egr3(-/-) and wild-type (WT) mice explored novel spatial environments and were sacrificed either immediately or after 5, 60, 240, or 480 minutes, and Arc expression was quantified by fluorescence in situ hybridization...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28586021/construction-and-characterization-of-a-transmembrane-eukaryotic-expression-vector-based-on-the-membrane-domain-structure-of-tnf-%C3%AE
#17
Fa Wang, Liang Zeng, Yue-Li Wang, Shi-Quan Cui, Liang Hu, Jun-Ming Zheng, Di-Nan Huang, Gan Hou
The aim of the present study was to construct a fast-acting, eukaryotic expression vector in eukaryotic cells based on transmembrane-tumor necrosis factor‑α (TM‑TNF‑α) structure. Two types of recombinant eukaryotic expression vectors were constructed, pcDNA3.1-TM-enterokinase-TNF‑α and pcDNA3.1‑TM‑Factor Xa‑TNF‑α, according to the TNF‑α transmembrane segments. Following the generation of these vectors, mouse embryonic 3T3 fibroblasts were transfected and reverse transcription‑polymerase chain reaction and western blotting analyses were used to analyze mTNF‑α mRNA and protein expression levels, respectively, in total cellular protein extracts and extracellular fluid...
June 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#18
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
#19
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/28575099/differential-stability-of-therapeutic-peptides-with-different-proteolytic-cleavage-sites-in-blood-plasma-and-serum
#20
Roland Böttger, Ralf Hoffmann, Daniel Knappe
Proteolytic degradation of peptide-based drugs is often considered as major weakness limiting systemic therapeutic applications. Therefore, huge efforts are typically devoted to stabilize sequences against proteases present in serum or plasma, obtained as supernatants after complete blood coagulation or centrifugation of blood supplemented with anticoagulants, respectively. Plasma and serum are reproducibly obtained from animals and humans allowing consistent for clinical analyses and research applications...
2017: PloS One
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