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Pharmacogenomics 2020 Jun 19. Epub 2020 Jun 19.

Department of Electrocardiogram Room, 900 Hospital of The Joint Logistics Team, 156 North Road, West 2nd Ring Road, Fuzhou, Fujian 350000, PR China.

This study was conducted to investigate the effects of , , and  and nongenetic factors on warfarin maintenance dose in a very elderly, frail Han-Chinese population.  16 variants of , , and were genotyped. Univariate analysis and multivariable regression model were performed for the associations of gene variants and warfarin maintenance dose. Read More

Sci Rep 2020 Apr 24;10(1):6988. Epub 2020 Apr 24.

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Korea.

This prospective, single-blind, randomized study was designed to evaluate the effect of genotype-based warfarin dosing compared with standard warfarin dosing in Korean patients with mechanical cardiac valves. Patients were assigned to either the genotype-based dosing group or the standard dosing group using stratified block randomization. The genotype-based dosing equation was adopted from a previous study which included VKORC1 rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, and age. Read More

Front Pharmacol 2020 6;11:325. Epub 2020 Apr 6.

Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile.

Background: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. Read More

Clin Transl Sci 2020 Apr 9. Epub 2020 Apr 9.

Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Precise dosing of warfarin is important to achieve therapeutic benefit without adverse effects. Pharmacogenomics explains some interindividual variability in warfarin response, but less attention has been paid to drug-drug interactions in the context of genetic factors. We investigated retrospectively the combined effects of cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex (VKORC)1 genotypes and concurrent exposure to CYP2C9-interacting drugs on long-term measures of warfarin anticoagulation. Read More

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620909154

Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):401-404

Qingdao Fuwai Cardiovascular Hospital, Qingdao, Shandong 266034, China.

Objective: To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population.

Methods: One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Read More

J Clin Pharm Ther 2020 Jun 13;45(3):547-560. Epub 2020 Mar 13.

Pharmaceutical Consultant, Gerrards Cross, UK.

What Is Known And Objective: Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its clinical implementation. The objective of this critique is to re-evaluate key warfarin pharmacogenetic studies with a view to explaining why this may be so.

Methods: Major widely-cited warfarin pharmacogenetic studies as well as recent meta-analyses were identified and a critical analysis of these was undertaken to identify factors that may account for poor clinical implementation of pre-treatment genotyping. Read More

Front Pharmacol 2019 17;10:1527. Epub 2020 Jan 17.

Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

The and genotypes are associated with anticoagulation control and the clinical events in warfarin therapy. However, the clinical utility of gene-based warfarin dosing (GBWD) is controversial. We compared the anticoagulation control and clinical events related to warfarin with GBWD to those with clinically fixed dosing (CFD). Read More

Pharmacogenomics J 2020 Feb 6. Epub 2020 Feb 6.

State Medical Academy, Nizhniy Novgorod, Russian Federation.

A total of 263 warfarin naive patients with indications to long-term anticoagulation were included in prospective multicenter study and randomized into Pharmacogenetics and Standard dosing groups. The loading warfarin dose in Pharmacogenetics group was calculated by Gage algorithm and corrected starting on day 5 of treatment according to INR. In Standard dosing group warfarin initial dose was 5 mg and starting on day 3 of treatment it was titrated according to INR. Read More

Pharmacogenomics 2020 03 24;21(4):257-267. Epub 2020 Jan 24.

Inter-University Centre for Genomics & Gene Technology, Department of Biotechnology, University of Kerala, Trivandrum-695 581, Kerala, India.

The role of mirSNPs in the 3'UTR of and genes that could influence warfarin dose variability via a discrete miRNA-mediated mechanism remains unexplained. Genotypic data in the 1000 Genomes dataset were analyzed for pair-wise linkage disequilibrium and allelic enrichment. MirSNP rs7294 in the 3'UTR of gene displayed varying strengths of linkage disequilibrium with rs9923231 and rs9934438 across populations, albeit consistently associated with higher warfarin dose requirements based on genome-wide association studies, meta-analysis and population-based association studies. Read More

Saudi J Biol Sci 2020 Jan 23;27(1):456-459. Epub 2019 Nov 23.

Department of Pharmacy Practice, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Saudi Arabia.

Warfarin doses are greatly affected by polymorphism altering cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) gene. This study evaluated the prevalence of alleles (either single or double) and carriers of single nucleotide polymorphisms (SNPs) in both genotypes CYP2C9 and VKORC1 in alkharj area, Saudi Arabia and its association with warfarin use risk. Total 112 samples were collected and genotyped using FlexiGene DNA Kit for isolation and StepOnePlus Real-Time PCR System by TaqMan allelic discrimination methods. Read More

Pharmacotherapy 2020 02 14;40(2):142-152. Epub 2020 Jan 14.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.

Objectives: Implementing pharmacogenetics for very important pharmacogenes (VIPs) holds the promise of improving clinical outcomes through optimal medication selection and dosing. However, significant differences in the frequency of actionable variants in VIPs may exist within subpopulations of a given ancestral group. Furthermore, these differences can potentially impact drug selection and dosing. Read More

Clin Pharmacol Ther 2020 Jun 28;107(6):1420-1433. Epub 2020 Jan 28.

Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalized Medicine, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Read More

Ann Lab Med 2020 May;40(3):216-223

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with 1173C. Read More

Pharmacogenomics J 2020 04 25;20(2):277-284. Epub 2019 Oct 25.

Qatar University, Doha, Qatar.

The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. Read More

Pediatr Cardiol 2019 Dec 5;40(8):1735-1744. Epub 2019 Oct 5.

Department of Pharmacy, University Hospitals of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK.

Warfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. Read More

Iran J Pharm Res 2019 ;18(2):1010-1019

National Hemophilia Center, Department of Hematology and Transfusion Medicine, Faculty of Medicine of the Comenius University and University Hospital, Bratislava, Slovak Republic.

A high prevalence of genetic polymorphisms increases sensitivity to warfarin therapy. In this study, we investigated 47 patients with effective long-term therapy by warfarin well-controlled by monitoring of International Normalised Ratio (INR). All patients were tested for gene polymorphisms VKORC1, CYP2C9*C2, and CYP2C9*C3, which were used for a dose calculation employing a program www. Read More

Sci Rep 2019 09 6;9(1):12856. Epub 2019 Sep 6.

Easton Cardiovascular Associates, Easton, PA, USA.

Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the therapeutic dose. Complications from inappropriate warfarin dosing are one of the most common reasons for emergency room visits. Approximately one third of warfarin dose variability results from common genetic variants. Read More

Eur J Clin Pharmacol 2019 Dec 23;75(12):1685-1693. Epub 2019 Aug 23.

Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, China.

Purpose: Factors influencing responsiveness to warfarin at treatment onset time were not well identified in Chinese patients undergoing heart valve replacement. We sought to select the most relevant factors that associated with patient response to warfarin early after heart valve surgery.

Methods: In this observational study, 289 patients starting warfarin therapy early after heart valve replacement surgery were enrolled. Read More

Am J Health Syst Pharm 2019 02;76(6):387-397

Clinical Pharmacy Services, Marshfield Clinic Health Systems, Marshfield, WI.

Purpose: As a preliminary evaluation of the outcomes of implementing pharmacogenetic testing within a large rural healthcare system, patients who received pre-emptive pharmacogenetic testing and warfarin dosing were monitored until June 2017.

Summary: Over a 20-month period, 749 patients were genotyped for VKORC1 and CYP2C9 as part of the electronic Medical Records and Genomics Pharmacogenetics (eMERGE PGx) study. Of these, 27 were prescribed warfarin and received an alert for pharmacogenetic testing pertinent to warfarin; 20 patients achieved their target international normalized ratio (INR) of 2. Read More

Clin Appl Thromb Hemost 2019 Jan-Dec;25:1076029619870252

3 Prince Iman Center for Research and Laboratory Sciences, King Hussein Medical Center (KHMC), Royal Medical Services (RMS), Amman, Jordan.

Multiple factors such as vitamin K consumption, drug interactions, herbs interactions, disease states, and alcohol intake affect international normalized ratio (INR) values and thus warfarin dosing. These variables have been described in general and for all patients in the literature. In contrast, the factors that affect INR control in a specific population are rarely studied. Read More

Ther Drug Monit 2019 12;41(6):748-754

Department of Clinical Laboratory, Wuhan Asia Heart Hospital, Wuhan University.

Background: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved.

Methods: A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. Read More

J Cardiovasc Pharmacol Ther 2019 11 7;24(6):521-533. Epub 2019 May 7.

9 Department of Clinical Pharmacy, University of Southern California, Los Angeles, CA, USA.

Introduction: Many warfarin-related genotypes have shown to impact the average daily warfarin (ADW) dose requirements; however, information in non-Caucasian populations is limited.

Objectives: To identify the frequencies of 4 warfarin-related gene polymorphisms in an ethnically diverse patient population and to examine their impact with other clinical variables on ADW dose requirements.

Methods: Patients were recruited from 2 anticoagulation clinics in the Los Angeles area. Read More

Pharmacogenomics 2019 06 3;20(8):599-608. Epub 2019 May 3.

David Weatherall Chair of Medicine, University of Liverpool & Royal Liverpool & Broadgreen University Hospitals NHS Trust, Liverpool, UK.

Pharmacogenomics 2019 04 15;20(5):311-317. Epub 2019 Apr 15.

Molecular Immunopathology & Histocompatibility Unit, Onassis Cardiac Surgery Center, Athens, Greece.

Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the and the gene account for 30-50% of the variability in dosing requirements, and it has been proposed that genotyping of these loci could facilitate management of VKA therapy and minimize risk of overanticoagulation, even in very low doses. Read More

Br J Clin Pharmacol 2019 08 17;85(8):1684-1691. Epub 2019 Jun 17.

Coagulation Disorders Unit, Clinical Chemistry, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.

Aims: Warfarin dose requirement varies significantly. We compared the clinically established doses based on international normalized ratio (INR) among patients with severe thrombosis and/or thrombophilia with estimates from genetic dosing algorithms.

Methods: Fifty patients with severe thrombosis and/or thrombophilia requiring permanent anticoagulation, referred to the Helsinki University Hospital Coagulation Center, were screened for thrombophilias and genotyped for CYP2C9*2 (c. Read More

OMICS 2019 03;23(3):152-166

1 Pharmacogenomics and Drug Metabolism Research Group, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Coumarins such as warfarin are prescribed for prevention and treatment of thromboembolic disorders. Warfarin remains the most widely prescribed and an anticoagulant of choice in Africa. Warfarin use is, however, limited by interindividual variability in pharmacokinetics and a narrow therapeutic index. Read More

Clin Pharmacokinet 2019 08;58(8):1077-1089

Department of Biopharmaceutics, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose, Tokyo, 204-8588, Japan.

Background: Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown.

Methods: Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients.

Results: Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. Read More

Mol Biol Rep 2019 Apr 2;46(2):1825-1833. Epub 2019 Feb 2.

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

It was aimed to underline the importance and explain the meaning of genetic testing in warfarin dosing and investigate and evaluate the contributions of the CYP2C9, VKORC1, and CYP4F2 variants in a Turkish population. Two hundred patients were genotyped for CYP2C9 (rs1799853, rs1057910 and rs56165452), VKORC1 (rs9934438, rs8050894, rs9923231, rs7294 and rs2359612) and CYP4F2 (rs2108622), yet, only 127 patients were found suitable for further evaluation in terms of their personal response to warfarin due to long term usage and available INR and dose usage information. The DNA sequences were determined by the ABI PRISM 3100 Genetic Analyzer to 3130xl System (Applied Biosystems, Foster City, California). Read More

J Cardiovasc Pharmacol 2019 03;73(3):127-135

Department of Cardiology, The First Affiliated Hospital, Jinan University, Guangzhou, China.

Aims: To evaluate the efficacy and safety of using genetic information to guide warfarin dosing in the Chinese population.

Methods: This meta-analysis was conducted among the published, randomized, controlled trials (RCTs) in the Chinese population comparing genotype-guided warfarin dosing (PG group) with clinical or standard warfarin dosing (STD group). RCTs published on or before January 2018 were identified using the PubMed, Embase, Cochrane Library, CNKI, Chinese VIP database, and Chinese Wanfang database. Read More

Basic Clin Pharmacol Toxicol 2019 May 24;124(5):538-549. Epub 2019 Jan 24.

Research Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

We searched PubMed entries and the Lattes database of Brazilian Pharmacogenetics Network investigators, for pharmacogenetic/genomic (PGx) studies in the Brazilian population, focusing on the drugs and genes included in the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Warfarin was the most extensively studied drug in a PGx context: a genomewide association study targeting warfarin stable dose identified significant signals in VKORC1 and CYP2C9, several PGx dosing algorithms were developed based on these and other genes, and the implications of population admixture on extrapolation of dosing recommendations in the CPIC guidelines were examined. A study in renal transplanted patients disclosed association of CYP3A5*6 and CYP3A5*7 with tacrolimus dosing, which led to addition of these variants to CYP3A5*3 in the CPIC tacrolimus guideline. Read More

OMICS 2019 01 19;23(1):36-44. Epub 2018 Dec 19.

1 Pharmacogenomics and Drug Metabolism Research Group, Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .

Warfarin is a widely prescribed anticoagulant with a narrow therapeutic index. The rs12777823G>A single-nucleotide polymorphism (SNP) in the CYP2C gene cluster has been shown to influence optimal warfarin doses in African Americans. We report here effects of rs12777823G>A SNP on warfarin dose requirements in two South African population groups, black Africans (BA) and mixed ancestry (MA). Read More

J Physiol Pharmacol 2018 Aug 10;69(4). Epub 2018 Nov 10.

Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.

Predicting the clinical consequences of anticoagulant therapy by identifying gene variants could help in the risk assessment of thrombosis or bleeding before and after surgery and may result in choosing more beneficial therapy. This work provides an overview of pharmacogenetic data of commonly used anticoagulant medication. The review focuses on polymorphisms influencing the efficacy and safety of the parenteral and oral anticoagulants. Read More

Pharmgenomics Pers Med 2018 16;11:169-178. Epub 2018 Oct 16.

GENIUROS Research Group, Center For Research in Genetics and Genomics - CIGGUR, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia,

Purpose: Warfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. and gene polymorphisms affect warfarin metabolism and dosage. Read More

Pharmacogenomics 2018 11 22;19(17):1357-1371. Epub 2018 Oct 22.

Department of Neurology, School of Medicine, University of Alabama at Birmingham, AL 35294, USA.

Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Read More

PLoS One 2018 19;13(10):e0205872. Epub 2018 Oct 19.

Easton Cardiovascular Associates, Easton, PA, United States of America.

Warfarin dosing remains challenging due to narrow therapeutic index and highly individual variability. Incorrect warfarin dosing is associated with devastating adverse events. Remarkable efforts have been made to develop the machine learning based warfarin dosing algorithms incorporating clinical factors and genetic variants such as polymorphisms in CYP2C9 and VKORC1. Read More

Thromb Res 2018 11 1;171:167-170. Epub 2018 Oct 1.

Institute of Cellular Medicine, Newcastle University and Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, NE1 7RU, UK. Electronic address:

Introduction: Warfarin therapy is stopped for a fixed period prior to surgery to minimise risk of perioperative bleeding. However, anticoagulation subsides at varying rates among different patients. We evaluated the influence of genetic (CYP2C9 and VKORC1), patient and clinical factors on warfarin clearance and the decline in INR following warfarin withdrawal. Read More

Ann Thorac Surg 2018 12 8;106(6):1774-1781. Epub 2018 Sep 8.

Division of Cardiac Surgery, Key Laboratory on Assisted Circulation, Ministry of Health, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians.

Methods: A double-blind, randomized control trial was performed to compare a genotype-guided dosing algorithm (CYP2C9, VKORC1, and CYP4F2) with a clinical-guided one in the initiation treatment for patients with mechanical heart valves. Read More

JACC Basic Transl Sci 2018 Aug 28;3(4):545-549. Epub 2018 Aug 28.

Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.

The U.S. Food and Drug Administration recently marked 10 years since first updating the labeling for warfarin (often referred to as the "poster child" of pharmacogenomics) to include information regarding the potential impact of and genetic variation on warfarin dosing requirements and risks. Read More

Pediatr Cardiol 2019 Jan 18;40(1):29-37. Epub 2018 Aug 18.

Department of Cardiology, Children's Hospital of Chongqing Medical University; Ministry of Education Key Laboratory of Child Development and Disorders, 136# Zhongshan 2nd Rd. Yuzhong District, Chongqing, 400014, China.

Long-term oral warfarin is recommended in pediatric Kawasaki disease patients with large coronary artery aneurysms; however, heterogeneity is considerable. This study aimed to determine variables affecting warfarin dosage in Kawasaki disease. The enrolled individuals (194 children) were divided into four groups: (1) Cases with severe coronary artery lesions (CAL) of IV to V degrees or thrombogenesis treated with oral warfarin were assigned to Group A; (2) Group B, CAL of I degrees; (3) Group C, CAL of II and III degrees cases with small or medium-sized CAL not treated with warfarin; (4) Group D, normal children without Kawasaki disease. Read More

BMC Med 2018 07 10;16(1):104. Epub 2018 Jul 10.

Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.

Background: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.

Methods: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. Read More

J Thromb Haemost 2018 09 17;16(9):1732-1742. Epub 2018 Jul 17.

Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.

Essentials A pediatric pharmacogenetic dosing algorithm for acenocoumarol has not yet been developed. We conducted a multicenter retrospective follow-up study in children in the Netherlands. Body surface area and indication explained 45. Read More

Blood Coagul Fibrinolysis 2018 Sep;29(6):496-500

Clinical Pharmacology Section, Internal Medicine Department.

: Coumadin oral anticoagulants are widely used in multiple clinical scenarios. Their narrow therapeutic range and a dosing strategy based on 'a posteriori' algorithms, pose them as an interesting group for prediction modelling research. Extensive literature explaining the association between clinical and genetic variables with the dose of warfarin have been published. Read More

Thromb Res 2018 07 8;167:32-36. Epub 2018 May 8.

Pediatric Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address:

Introduction: Warfarin therapy is recommended in children with giant coronary artery aneurysms (GCAAs) after Kawasaki disease (KD). Large individual variability makes it difficult to predict the warfarin dose. Polymorphisms in the vitamin K expoxide reductase 1 (VKORC1) and cytochrome P4502C9 (CYP2C9) genes have been reported to influence the warfarin dose. Read More

Br J Clin Pharmacol 2018 09 21;84(9):1868-1882. Epub 2018 Jun 21.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People's Republic of China.

Aims: Previous trials on the effectiveness of genotype-guided warfarin dosing vs. conventional dosing have been inconclusive. We conducted a systematic review and meta-analysis of randomized trials comparing genotype-guided to conventional dosing strategies. Read More

Indian J Hematol Blood Transfus 2018 04 27;34(2):328-336. Epub 2016 Sep 27.

3Biochemistry Department, Pharos University in Alexandria, Alexandria, Egypt.

Warfarin is the most commonly used drug for chronic prevention of thromboembolic events, it also ranks high among drugs that cause serious adverse events. The variability in dose requirements has been attributed to inter-individual differences in medical, personal, and genetic factor. Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin by catalyzing the conversion of the pharmacologically more potent S-enantiomer to its inactive metabolites. Read More

Ther Drug Monit 2018 06;40(3):362-368

Department for Pharmacogenomics and Therapy Individualization, University Hospital Center Zagreb, Zagreb, Croatia.

Background: Observational studies have indicated potential benefits of CYP2C9- and VKORC1-guided dosing of warfarin but randomized clinical trials have resulted in contradictory findings. One of the reasons for contradiction may be the negligence of possible differences between warfarin indications. This study aims to determine efficacy and safety of genotype-guided and clinically guided dosing of warfarin in atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first 5 days after the introduction of therapy. Read More

Cardiovasc Ther 2018 Apr 3;36(2). Epub 2018 Jan 3.

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Aim: This study was conducted to compare predictive accuracy of the available pharmacogenetics (PGx)-guided warfarin dosing algorithms derived from Caucasian, Asian, and mixed population to identify a suitable algorithm for Thai population.

Methods: Ten warfarin dosing algorithms derived from different population including Caucasian, East Asian, South-East Asian, and mixed races were selected and tested with clinical and genetic data of Thai patients. Comparative performances of these algorithms were tested using mean dose error (MDE) between actual warfarin maintenance dose (AWMD) and predicted dose generated by each dosing algorithm, and percentage of ideal dose prediction (IDP). Read More

Lab Med 2017 Dec;49(1):25-34

Department of Cardiac Surgery, Madani Heart Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

Many lines of evidence suggest that warfarin dosing variability is significantly associated with cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles. Therefore, we investigated the influence of CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms on warfarin dose requirements in patients who underwent cardiac valve surgery during the postoperative period.A total of 100 patients with heart valve replacement who had a prescribed target international normalized ratio (INR) range of 2-3 were enrolled in the study. Read More