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Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.
Li, B, Liu, R, Wang, C, Ren, C, Zhang, S, Zhang, F, Zhang, J, Liu, S, Wei, Y, Liu, W, et al
European journal of clinical pharmacology. 2019;(12):1685-1693
Abstract
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. CYP2C9 *1, *2, *3, and *5; VKORC1-1639 G>A, CYP4F2 V433M, and GGCX rs11676382 genotypes; clinical characteristics, response to therapy, and bleeding and thrombosis events were collected. The primary outcomes were the time to the first INR equal to or more than lower limit of therapeutic range and the warfarin dose requirements. Stepwise multiple linear regression was performed to develop a dosing algorithm to predict the warfarin dose requirements. RESULTS The results of univariate analysis showed lone VKORC1-1639 G>A, CYP2C9 *1/*3, cefazolin, cefoperazone-sulbactam, increased BMI, Δhemoglobin, and white blood cell count could significantly affect patient responsiveness to warfarin in the initial period of anticoagulation. Multivariate analysis resulted in an equation: Accumulated warfarin doses (mg) = 17.068 VKORC1-1639 G>A - 4.261 hypertension + 0.593 BMI - 0.115 age - 4.852 CYP2C9 *1/*3 - 2.617 cefazolin - 4.902 cefoperazone-sulbactam - 4.537, which could explain 40.2% of the variability in warfarin dose needed to reach the first INR equal to or more than lower limit of therapeutic range. CONCLUSIONS Both genetic and clinical factors contributed to anticoagulation effect of warfarin in the initial period of treatment. Our findings could provide a basis for the personalized management of warfarin use in the early stage of anticoagulation in northern Chinese patients.
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Quality Appraisal of Guidelines on Cancer-Associated Thrombosis Using AGREE II Instrument and Analysis of Current Status of New Oral Anticoagulants.
Zhang, J, Xu, J, Zhang, W, Jiang, M, Liu, J, Xu, L, Liu, G, Zhao, Z
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2019;:1076029619846562
Abstract
Cancer-associated thrombosis (CAT) studies have increased in recent years and the quality of guidelines to guide the clinical practice of CAT prevention and treatment becomes crucial. The therapy status of new oral anticoagulants (NOACs) has been established in some thrombotic diseases, but the evidence for CAT remains unconvincing. The aim of this research is to evaluate the quality of CAT guidelines and discuss the role of NOAC in CAT. A search of articles was performed using PubMed/Medline, Chinese National Knowledge Infrastructure, and other authoritative websites. Search terms included guideline or guidance, consensuses, cancer, and thrombosis. Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool was used to evaluate the qualities of the guidelines. A total of 19 guidelines were screened out and evaluated, of which 8 were recommended, 5 were recommended after revision, and 6 were not recommended. For prevention and treatment of CAT, low-molecular-weight heparin is the most recommended, followed by vitamin K antagonist, unfractionated heparin, fondaparinux, and aspirin. New oral anticoagulant is optional in some cases of CAT treatment. Based on AGREE II assessment tool, the quality of CAT guidelines is inconsistent. Attention should be drawn to the quality of CAT guidelines during clinical practice. The role of NOAC in the treatment of CAT is gradually established but requires more supporting evidence from future clinical trials.
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Heparinized saline versus normal saline for maintaining peripheral venous catheter patency in China: An open-label, randomized controlled study.
Xu, L, Hu, Y, Huang, X, Fu, J, Zhang, J
The Journal of international medical research. 2017;(2):471-480
Abstract
Objective To evaluate the effects of heparin saline versus normal saline as locking solution for maintaining patency in peripheral venous catheters in Chinese patients. Methods This open-label, randomized controlled study was conducted in two hepatobiliary surgery wards, where patients received identical treatments, at a tertiary referral hospital. Patients were randomly divided into a normal saline group (NS, 3 ml) or a heparin saline group (HS, 50 IU/ml, 3 ml) for catheter sealing. Results The study enrolled 286 patients and 609 peripheral venous catheters were included in the analysis. The patients in the two groups had no local infections or catheter-related bloodstream infections. There were no significant differences between the two groups in terms of the rate of catheter obstruction, duration time, or the rates of phlebitis, infiltration, and accidental catheter removal. Conclusions No significant differences in the peripheral venous catheter sealing effects were observed between normal saline and heparin saline usage in Chinese patients.
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Non-Vitamin K Antagonist Oral Anticoagulants: The Clinician's New Challenge.
Yorkgitis, BK, Zhang, J, Rappold, JF
The Journal of the American Osteopathic Association. 2015;(10):612-21
Abstract
Millions of US patients are prescribed oral anticoagulants. Traditionally, oral anticoagulation was achieved with vitamin K antagonists (VKAs). In recent years, non-VKA oral anticoagulants (NOACs) have emerged that provide an effective and convenient alternative to VKAs. These agents possess very different pharmacologic properties from what the medical community has grown accustom to with the VKAs. Thus, a new knowledge base is required for NOACs. One particular challenge with the NOACs is the lack of specific reversal agent, resulting in difficulties correcting the coagulopathy induced by these drugs when needed. A review of the current literature is presented to assist clinicians in gaining knowledge of the NOACs to care for patients.
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The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis.
Zhang, J, Tian, L, Zhang, Y, Shen, J
Thrombosis research. 2015;(5):955-61
Abstract
INTRODUCTION Warfarin is the most commonly used oral anticoagulant, however, there are large interindividual variations in dose responses. Genetic polymorphisms in CYP2C9, VKORC1 and CYP4F2 have been shown to play an important role in variations in the warfarin maintenance dose in adults, but their effects in children remain unclear. We aimed to investigate the effect of VKORC1 polymorphism on warfarin dosage in pediatric patients by meta-analysis. MATERIALS AND METHODS Using strict inclusion and exclusion criteria, we searched PubMed, EMBASE, Cochrane library, Chinese Biomedical Literature Database, CNKI and ChainInfo from 2004 to Mach 17th, 2015. The relationship between warfarin dose and two single nucleotide polymorphisms of the VKORC1 gene (at positions -1639 and 1173) were analyzed using Revman version 5.2.3 software. RESULTS AND CONCLUSIONS Eight studies were included in the meta-analysis, involving 610 pediatric patients. Patients that were VKORC1 -1639 GA, AA or A carriers required significantly lower warfarin dosage than GG carriers (the weighted mean difference in warfarin dose ranged from -26% to -50%). Additionally, the age of the patient and indication of warfarin (i.e. Fontan procedure) significantly affected warfarin dosage, but changes in the target international normalized ratio range had no effect. On the other hand, VKORC1 1173 polymorphisms showed no significant effect on warfarin dosage, which differs from adult patients. In conclusion, we found that VKORC1 -1639 gene polymorphisms have a moderate effect on warfarin dosage in pediatric patients, but clinical characteristics such as age and indication of warfarin also play an important role.
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Efficacy and safety of adjunctive anticoagulation in patients with lung cancer without indication for anticoagulants: a systematic review and meta-analysis.
Zhang, J, Zhang, YL, Ma, KX, Qu, JM
Thorax. 2013;(5):442-50
Abstract
BACKGROUND Patients with lung cancer are at high risk of venous thromboembolism (VTE), and VTE predicts a poor prognosis. Anticoagulation therefore might be beneficial for these patients. It is not clear whether anticoagulants could improve survival and other outcomes in patients with lung cancer with no indication for anticoagulation. METHODS We searched the Web of Science, Medline, EMBASE and Cochrane databases for relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcomes were 1-year survival and incidence of VTE. Pooled risk ratios (RR) were calculated using control as a reference group and significance was determined by the Z test. RESULTS Nine eligible studies with 2185 participants were included. Anticoagulation showed significant improvement in survival at 1 year (RR 1.18, 95% CI 1.06 to 1.32; p=0.004) and at 2 years (RR 1.27, 95% CI 1.04 to 1.56; p=0.02), but not at 6 months. Subgroup analysis showed a survival benefit for patients with small cell lung cancer (SCLC) and those with non-advanced/limited cancer. The incidence of VTE (RR=0.55, 95% CI 0.31 to 0.97; p=0.04) and thromboembolic events (RR=0.48, 95% CI 0.28 to 0.82; p=0.008) was reduced with anticoagulation. Both vitamin K antagonist (VKA) and subcutaneous heparin increased the risk of haemorrhage, but heparin did not increase the incidence of major bleeding. CONCLUSIONS Anticoagulation showed a survival benefit, especially for those with SCLC and prolonged life expectancy, and reduced the risk of VTE in lung cancer patients with no indication for anticoagulants. Subcutaneous heparin is superior to VKA because of a potentially smaller risk of major bleeding.