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https://www.readbyqxmd.com/read/27918545/warfarin-traps-human-vitamin-k-epoxide-reductase-in-an-intermediate-state-during-electron-transfer
#1
Guomin Shen, Weidong Cui, Hao Zhang, Fengbo Zhou, Wei Huang, Qian Liu, Yihu Yang, Shuang Li, Gregory R Bowman, J Evan Sadler, Michael L Gross, Weikai Li
Although warfarin is the most widely used anticoagulant worldwide, the mechanism by which warfarin inhibits its target, human vitamin K epoxide reductase (hVKOR), remains unclear. Here we show that warfarin blocks a dynamic electron-transfer process in hVKOR. A major fraction of cellular hVKOR is in an intermediate redox state containing a Cys51-Cys132 disulfide, a characteristic accommodated by a four-transmembrane-helix structure of hVKOR. Warfarin selectively inhibits this major cellular form of hVKOR, whereas disruption of the Cys51-Cys132 disulfide impairs warfarin binding and causes warfarin resistance...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27914497/acute-management-of-stroke-patients-taking-non-vitamin-k-antagonist-oral-anticoagulants-addressing-real-world-anticoagulant-management-issues-in-stroke-aramis-registry-design-and-rationale
#2
Ying Xian, Adrian F Hernandez, Tina Harding, Gregg C Fonarow, Deepak L Bhatt, Robert E Suter, Yosef Khan, Lee H Schwamm, Eric D Peterson
BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27909544/reducing-the-risk-of-stroke-in-patients-with-nonvalvular-atrial-fibrillation-with-direct-oral-anticoagulants-is-one-of-these-not-like-the-others
#3
REVIEW
Paul P Dobesh Pharm D, John Fanikos Mba R Ph
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27861698/influence-of-competing-risks-on-estimating-the-expected-benefit-of-warfarin-in-individuals-with-atrial-fibrillation-not-currently-taking-anticoagulants-the-anticoagulation-and-risk-factors-in-atrial-fibrillation-study
#4
Jeffrey M Ashburner, Alan S Go, Yuchiao Chang, Margaret C Fang, Lisa Fredman, Katie M Applebaum, Daniel E Singer
OBJECTIVES: To provide greater understanding of the "real world" effect of anticoagulation on stroke risk over several years. DESIGN: Cohort study. SETTING: Anticoagulation and Risk Factors in Atrial Fibrillation Study community-based cohort. PARTICIPANTS: Adults with nonvalvular atrial fibrillation (AF) between 1996 and 2003 (13,559). MEASUREMENTS: All events were clinician adjudicated. Extended Cox regression with longitudinal warfarin exposure was used to estimate cause-specific hazard ratios (HRs) for thromboembolism and the competing risk event (all cause death)...
November 12, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27811436/understanding-the-records-3-trial-and-its-impact-on-anticiagulation-practice-in-resource-poor-countries
#5
REVIEW
T U Nwagha, H E Omunakwe
Venous thromboembolism is a significant cause of mortality and morbidity in patients following major orthopaedic surgeries. The RECORDS 3 trial revolutionised anticoagulation practice especially in patients with total knee arthroplasty and challenging the strong hold of warfarin and heparin in anticoagulation practice. With all these novel agents shifting the paradigm in anticoagulation management, Cost, in accessibility and lack of awareness of the availability of the agents amongst clinicians and surgeons alike are some factors militating against the use of these agents in patients in resource poor countries...
November 2016: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/27794621/insights-into-the-thermodynamics-of-polymer-nanodot-human-serum-albumin-association-a-spectroscopic-and-calorimetric-approach
#6
Arpan Bhattacharya, Somnath Das, Tushar Kanti Mukherjee
With the advent of newer luminescent nanoparticles (NPs) for bioimaging applications, their complex interactions with the individual biomolecules need to be understood in great detail, prior to their direct application into the cellular environments. Here we have present a systematic and detailed study of the interaction between luminescent polymer nanodot (PND) and human serum albumin (HSA) in its free and ligand-bound state with the help of spectrophotometric and calorimetric techniques. At physiological pH (pH=7...
October 30, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27768243/prenatal-exposure-to-environmental-factors-and-congenital-limb-defects
#7
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/27767380/landscape-of-warfarin-and-clopidogrel-pharmacogenetic-variants-in-qatari-population-from-whole-exome-datasets
#8
Ambily Sivadas, Parul Sharma, Vinod Scaria
AIM: Pharmacogenetic landscapes of commonly used antiplatelet drugs, warfarin and clopidogrel have been studied in-depth in many countries. However, there is a paucity of data to understand their patterns in the Arab populations. MATERIALS & METHODS: We analyzed the whole exome sequencing datasets of 100 Qatar individuals available in public domain with this perspective. RESULTS: We characterized the allelic distribution of variants routinely tested for warfarin and clopidogrel...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27766064/characteristics-of-taiwanese-patients-of-pnh-in-the-international-pnh-registry
#9
Wen-Chien Chou, Wei-Han Huang, Ming-Chung Wang, Chao-Sung Chang, Shih-Peng Yeh, Tzeon-Jye Chiou, Yeu-Chin Chen, Tseng-Hsi Lin, Ming-Ching Shen
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and acquired hematopoietic stem cell disease, with florid clinical presentations. Although this disease has been characterized in the western countries, its clinical and laboratory features in Taiwan have not yet been reported. RESULTS: As a part of an international prospective, non-interventional, observational registration trial of PNH, we have analyzed 63 patients recruited between 2009 and 2015 in Taiwan, with comparison to the 3857 patients in the rest of the world (ROW)...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27714756/cardiovascular-pharmacogenetics-a-promise-for-genomically-guided-therapy-and-personalized-medicine
#10
REVIEW
M Zaiou, H El Amri
Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered...
October 6, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27704588/assessment-of-web-based-education-resources-informing-patients-about-stroke-prevention-in-atrial-fibrillation
#11
E Pandya, B V Bajorek
WHAT IS KNOWN AND OBJECTIVE: The importance of 'shared decision-making' is much emphasized in recent clinical guidelines regarding stroke management in atrial fibrillation (AF), more so following the inclusion of non-vitamin K oral anticoagulants (NOACs) among the treatment options. It is important that patients are navigated through balanced and unbiased information about the available treatment options, so as to understand the risk and benefits associated with the therapies, and to enable them to accordingly communicate their concerns and views with their clinicians prior to therapy selection...
October 5, 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27693993/the-c-of-chads-historical-perspective-and-clinical-applications-for-anticoagulation-in-patients-with-non-valvular-atrial-fibrillation-and-congestive-heart-failure
#12
Y Chugh, R T Faillace
The risk stratification of patients with coexisting non valvular atrial fibrillation and congestive heart failure, is often a clinical challenge, as the definitions of congestive heart failure in the popular CHADS2 and CHA2DS2VASc scoring systems, and amongst major clinical trials on Warfarin and Novel Oral Anticoagulants (NOAC) have heterogeneity. Available evidence reveals that any heart failure and/or left ventricular systolic dysfunction is associated with higher rates of stroke/systemic embolism and bleeding in patients with non valvular atrial fibrillation compared to patients without heart failure and normal left ventricular function...
December 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27688985/cardiovascular-disease-death-before-age-65-in-168-countries-correlated-statistically-with-biometrics-socioeconomic-status-tobacco-gender-exercise-macronutrients-and-vitamin-k
#13
David K Cundiff, Paul S Agutter
BACKGROUND: Nutrition researchers recently recognized that deficiency of vitamin K2 (menaquinone: MK-4-MK-13) is widespread and contributes to cardiovascular disease (CVD). The deficiency of vitamin K2 or vitamin K inhibition with warfarin leads to calcium deposition in the arterial blood vessels. METHODS: Using publicly available sources, we collected food commodity availability data and derived nutrient profiles including vitamin K2 for people from 168 countries...
August 24, 2016: Curēus
https://www.readbyqxmd.com/read/27667379/a-review-of-the-clinical-subgroup-analyses-from-the-re-ly-trial
#14
Rohit Kumar, Aref M Rahman, Brian L Henry
Dabigatran was the first direct-acting oral anticoagulant approved by the US Food and Drug Administration for prevention of stroke and systemic embolism in people with atrial fibrillation, based on data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Over 18,000 patients with nonvalvular atrial fibrillation and a moderate-to-high risk of thromboembolic stroke were randomized to warfarin or dabigatran. With respect to the primary endpoints for efficacy and safety, dabigatran was superior to warfarin in the prevention of stroke and thromboembolism and noninferior with respect to major bleeding...
2016: Reviews in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27665207/factors-associated-with-resource-utilization-and-coronary-artery-dilation-in-refractory-kawasaki-disease-from-the-pediatric-health-information-system-database
#15
Jennifer Y Lo, L LuAnn Minich, Lloyd Y Tani, Jacob Wilkes, Qian Ding, Shaji C Menon
Management guidelines for refractory Kawasaki disease (KD) are vague. We sought to assess practice variation and identify factors associated with large/complex coronary artery aneurysms (LCAA) and resource utilization in refractory KD. This retrospective cohort study identified patients aged ≤18 years with KD (2004 to 2014) using the Pediatric Health Information System. Refractory KD was defined as receiving >1 dose of intravenous immunoglobulin. Demographics, medications, concomitant infections, length of stay (LOS), and charges were collected...
August 31, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/27665101/combined-aspirin-and-anticoagulant-therapy-in-patients-with-atrial-fibrillation
#16
Charlotte H So, Mark H Eckman
The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD...
September 24, 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27639441/human-teratogens-and-genetic-phenocopies-understanding-pathogenesis-through-human-genes-mutation
#17
Matteo Cassina, Giulia A Cagnoli, Daniela Zuccarello, Elena Di Gianantonio, Maurizio Clementi
Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans...
September 14, 2016: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27594818/novel-oral-anticoagulants-for-venous-thromboembolism-with-special-emphasis-on-risk-of-hemorrhagic-complications-and-reversal-agents
#18
Zaheer Ahmed, Seemeen Hassan, Gary A Salzman
Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes...
April 2016: Current Drug Therapy
https://www.readbyqxmd.com/read/27578223/adverse-events-associated-with-the-use-of-direct-acting-oral-anticoagulants-in-clinical-practice-beyond-bleeding-complications
#19
Emanuel Raschi, Matteo Bianchin, Walter Ageno, Roberto De Ponti, Fabrizio De Ponti
Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered the market in 2008 with the expected breakthrough potential of circumventing limitations related to treatment with vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although data derived from premarketing randomized clinical trials have largely demonstrated the clinical benefit of DOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safety in the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy, in order to assess the actual risk-benefit profile...
August 25, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27548686/reversal-agents-for-direct-oral-anticoagulants-understanding-new-and-upcoming-options
#20
Kelly C Rogers, Melanie P Shelton, Shannon W Finks
Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials...
November 2016: Cardiology in Review
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