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https://www.readbyqxmd.com/read/28268853/optimal-decision-support-rules-improve-personalize-warfarin-treatment-outcomes
#1
Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28262345/influence-of-nr3c1-and-vdr-polymorphisms-on-stable-warfarin-dose-in-patients-with-mechanical-cardiac-valves
#2
Kyung Eun Lee, Jee Eun Chung, Boram Yi, Yoon Jeong Cho, Hyun Jeong Kim, Gwan Yung Lee, Joo Hee Kim, Byung Chul Chang, Hye Sun Gwak
OBJECTIVES: The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. METHODS: Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570)...
February 24, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28259826/medical-management-of-extensive-arterial-thromboembolism-in-a-patient-with-essential-thrombocythemia-and-warfarin-failure
#3
Aisha K Ahmed, Alicia Youssef, Nedaa Skeik
Chronic myeloproliferative disorders (CMPD) share a stem cell-derived clonal myeloproliferation. This group of disorders includes essential thrombocythemia (ET), polycythemia vera (PV), chronic myeloid leukemia (CML), and primary myelofibrosis (PMF), with the respective features of thrombocytosis, erythrocytosis, and bone marrow fibrosis(1). These disorders can be associated with genetic mutations affecting protein tyrosine kinases, resulting in different configurations of abnormal signal transduction. The Janus tyrosine kinase 2 (JAK2) mutation can be used as a key diagnostic tool for diagnosing MPDs, specifically, ET, PV, and PMF(2)...
March 1, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28227051/optimal-decision-support-rules-improve-personalize-warfarin-treatment-outcomes
#4
Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato, Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato, Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224948/predictors-of-warfarin-dose-requirements-in-south-african-patients-attending-an-anticoagulation-clinic
#5
Elise Schapkaitz, Johanna Sithole
INTRODUCTION: Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. MATERIALS AND METHODS: This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital...
March 2017: Journal of Vascular Nursing: Official Publication of the Society for Peripheral Vascular Nursing
https://www.readbyqxmd.com/read/28135054/integrated-analysis-of-genetic-variation-and-gene-expression-reveals-novel-variant-for-increased-warfarin-dose-requirement-in-african-americans
#6
Wenndy Hernandez, Eric R Gamazon, Keston Aquino-Michaels, Erin Smithberger, Travis J O'Brien, Arthur F Harralson, Matthew Tuck, April Barbour, Larisa H Cavallari, Minoli A Perera
BACKGROUND: Warfarin is commonly used to control and prevent thromboembolic disorders. However, due to warfarin's complex dose-requirement relationship, safe and effective use is challenging. Pharmacogenomics-guided warfarin dosing algorithms that include the well-established VKORC1 and CYP2C9 polymorphisms explain only a small proportion of inter-individual variability in African Americans (AAs). OBJECTIVES: We aimed to assess whether transcriptomic analyses could be used to identify regulatory variants associated with warfarin dose response in AAs...
January 30, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079798/clinical-and-genetic-factors-associated-with-warfarin-maintenance-dose-in-northern-chinese-patients-with-mechanical-heart-valve-replacement
#7
Rui Liu, Jian Cao, Qian Zhang, Xin-Miao Shi, Xiao-Dong Pan, Ran Dong
The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28074382/engaging-hmong-adults-in-genomic%C3%A2-and%C3%A2-pharmacogenomic-research-toward-reducing-health-disparities-in-genomic-knowledge-using-a-community-based-participatory-research-approach
#8
Kathleen A Culhane-Pera, Robert J Straka, MaiKia Moua, Youssef Roman, Pachia Vue, Kang Xiaaj, May Xia Lo, Mai Lor
Advancing precision medicine relies in part on examining populations that may exhibit unique genetic variants that impact clinical outcomes. Failure to include diverse populations in genomic-based research represents a health disparity. We implemented a community-based participatory research (CBPR) process with the Hmong community in Minnesota, who were refugees from Laos, in order to assess the feasibility of conducting genomic and pharmacogenomic-based research for genetic variants that are relevant to the Hmong community...
January 10, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28058824/the-effect-of-amiodarone-on-warfarin-anticoagulation-a-register-based-nationwide-cohort-study-involving-the-swedish-population
#9
J Holm, J D Lindh, M L Andersson, B Mannheimer
Essentials Data on the effect of introducing amiodarone in patients already using warfarin regime are scarce. Information on 754 patients was extracted from three nationwide registers in Sweden. With amiodaron, 37% of patients had an international normalized ratio (INR) over 3.0 To avoid bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring. SUMMARY: Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28049362/warfarin-dose-model-for-the-prediction-of-stable-maintenance-dose-in-indian-patients
#10
Tejasvita Gaikwad, Kanjaksha Ghosh, Peter Avery, Farhad Kamali, Shrimati Shetty
The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.*4A>G (rs1043550), EPHX1 c...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27999513/choosing-non-vitamin-k-antagonist-oral-anticoagulants-practical-considerations-we-need-to-know
#11
REVIEW
Alpesh Amin
BACKGROUND: Warfarin is a well-established agent for use in the prevention of stroke or systemic embolic event (SEE) in patients with nonvalvular atrial fibrillation (NVAF) and for the treatment of venous thromboembolism (VTE). However, management of patients requiring oral anticoagulation with warfarin can be complicated by the need for frequent monitoring, drug-drug and drug-food interactions, and a variable response based on genetic polymorphisms. The non-vitamin K antagonist oral anticoagulants (NOACs) were developed as alternatives to warfarin; they do not require routine monitoring and have predictable pharmacokinetics, fewer drug-drug interactions, and limited drug-food interactions...
2016: Ochsner Journal
https://www.readbyqxmd.com/read/27992547/the-impact-of-genetic-and-non-genetic-factors-on-warfarin-dose-prediction-in-mena-region-a-systematic-review
#12
Loulia Akram Bader, Hazem Elewa
BACKGROUND: Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing...
2016: PloS One
https://www.readbyqxmd.com/read/27990512/warfarin-genotyping-with-hybridization-induced-aggregation-on-a-poly-ethylene-terephthalate-microdevice
#13
Hillary S Sloane, Morgan B Carter, Alexa E C Cecil, Delphine Le Roux, Daniel L Mills, James P Landers
Warfarin, a commonly prescribed oral anticoagulant, is burdened by a narrow therapeutic index and high inter-individual variability in response, making it the second leading cause of drug-related emergency room visits. Since genetic factors contribute significantly to warfarin sensitivity, a genotype-guided dosing strategy may reduce the occurrence of adverse events. While numerous methods have been demonstrated for warfarin genotyping, the specifications of most assays with respect to turnaround time and cost are not ideal for routine testing...
December 19, 2016: Analyst
https://www.readbyqxmd.com/read/27938396/genetic-polymorphisms-of-patients-on-stable-warfarin-maintenance-therapy-in-a-ghanaian-population
#14
William Kudzi, Samuel Yao Ahorhorlu, Bartholomew Dzudzor, Edeghonghon Olayemi, Edmund Tetteh Nartey, Richard Harry Asmah
BACKGROUND: Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR...
December 9, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27925230/role-of-abc-transporters-in-trans-epithelial-transport-of-vitamin-k-antagonists
#15
Bernadette Espana, Solange Couturier, Caroline Prouillac
Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (phenindione, fluindione)...
January 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27879469/frequency-of-common-vkorc1-polymorphisms-and-their-impact-on-warfarin-dose-requirement-in-pakistani-population
#16
Aisha Qayyum, Muzammil Hasan Najmi, Qaisar Mansoor, Muhammad Irfan, Abdul Khaliq Naveed, Andleeb Hanif, Ali Raza Kazmi, Muhammad Ismail
Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations...
January 1, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27878474/quantitative-assessment-of-cyp2c9-genetic-polymorphisms-effect-on-the-oral-clearance-of-s-warfarin-in-healthy-subjects
#17
Chanan Shaul, Simcha Blotnick, Mordechai Muszkat, Meir Bialer, Yoseph Caraco
BACKGROUND: Genetic polymorphisms in CYP2C9 account for 10-20% of the variability in warfarin dose requirement. As such CYP2C9 genetic polymorphisms are commonly included in algorithms aimed to optimize warfarin therapy as a way to account for variability in warfarin responsiveness that is due to altered pharmacokinetics. However, most of the currently available pharmacokinetic data were derived from studies among patients on chronic warfarin therapy and therefore suffer from the confounding effects of disease states and drug interactions...
February 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27864383/use-of-pharmacogenetic-information-in-the-treatment-of-cardiovascular-disease
#18
REVIEW
Kevin Friede, Josephine Li, Deepak Voora
BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a family who required remarkably high warfarin doses (up to 145 mg/day, 20 times the average dose) to achieve appropriate anticoagulation. Since this time, pharmacogenetics has become a mainstay of cardiovascular science, and genetic variants have been implicated in several fundamental classes of medications used in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants that affect drug response to 3 classes of cardiovascular drugs: statins, platelet P2Y12 inhibitors, and anticoagulants...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27864202/implementation-of-inpatient-models-of-pharmacogenetics-programs
#19
Larisa H Cavallari, Craig R Lee, Julio D Duarte, Edith A Nutescu, Kristin W Weitzel, George A Stouffer, Julie A Johnson
PURPOSE: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27855643/evaluation-of-a-pharmacogenetic-based-warfarin-dosing-algorithm-in-patients-with-low-time-in-therapeutic-range-study-protocol-for-a-randomized-controlled-trial
#20
Leiliane Rodrigues Marcatto, Luciana Sacilotto, Carolina Tosin Bueno, Mirella Facin, Celia Maria Cassaro Strunz, Francisco Carlos Costa Darrieux, Maurício Ibrahim Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Junior Lima Santos
BACKGROUND: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital...
November 17, 2016: BMC Cardiovascular Disorders
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