Warfarin Dosing and Body Mass Index

Mueller, Julia A.; Patel, Tulsi; Halawa, Ahmad; Dumitrascu, Adrian; Dawson, Nancy L.

doi:10.1177/1060028013517541

Cited by 42 publications

(41 citation statements)

References 28 publications

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“…Wynne found negative correlation between age and dose (r = -0.53; P = < 0.001) and positive correlation between dose and liver volume (r = 0.49; P = 0.002), and that liver volume and age accounted for 43% of dose variability. Another study concluded that lower dose requirements in elderly are attributed to decreased hepatic clearance, 1% decrease per year (99). Increased sensitivity to warfarin in the elderly could be also attributed to reduced vitamin k intake or reduced absorption, which can decrease the capacity of the liver to synthesize clotting factors; or it could simply be a result of polypharmacy that can lead to drug-drug interaction, potentiating the effect of warfarin (100).…”

Section: Effect Of Studied Clinical Factors On Warfarin Dosementioning

confidence: 99%

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

et al. 2019

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Genetic and non-genetic factors were shown to affect warfarin dosing; however, their effect may vary from one population to the other. No previous studies were conducted on the Qatari population to elucidate these factors. Research question: What is the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants in Qataris? and what is their contribution to warfarin dose variability? Study design: An observational cross-sectional study Methods: Hundred and fifty warfarin-treated Qatari patients on a stable dose and a therapeutic INR for at least 3 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. Results: The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A 0.46, while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one loss of function CYP2C9 allele (*2 or *3) required significantly lower warfarin doses iv compared to non-carriers (24 mg/week vs. 34.1 mg/week, p<0.001). VKORC1 (-1639G>A) and CYP4F2*3 polymorphisms on the other hand were not associated with warfarin dose. Multivariate analysis on the derivation cohort showed that congestive heart failure (CHF) (P=0.002), and CYP2C9*2 & *3 (P<0.001) were associated with lower warfarin dose while smoking (P=0.003) was associated with higher warfarin dose. These factors explained 24.1% of warfarin dose variability in Qatari patients. CYP2C9*2 & *3 variants accounted for 11.8% of warfarin dose variability. In the validation cohort, correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient= 0.41, p=0.005). Conclusion: This study showed that CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with CHF and smoking. Dose reduction should be considered in patients with CHF and those carrying at least one of the CYP2C9*2 & *3 alleles. While dose increase should be considered in smokers. v DEDICATION To my loving family vi ACKNOWLEDGMENTS The completion of this thesis would not have been possible without the kind support and assistance of so many individuals whose names may not all be enumerated. All their efforts and contributions are highly and sincerely appreciated and acknowledged. At foremost, I want to thank GOD for giving me all the strength and good health to complete this work. I would like to extend my gratitude to my family; mom, dad, Aya & Tala, who never seemed to cease their support and reassurance even with distance keeping us apart. My beloved husband, Ammar who always believed in me and stood by my side every step of the way, my son Farouk for always being my source of joy and inspiration. I would like to extend my special thanks and gratitude to my supervisor Dr. Hazem F. Elewa for never being hesitant to share his knowledge and expertise with me, for always supporting and fostering my achievements, and always promoting me to stand out.

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Section: Effect Of Studied Clinical Factors On Warfarin Dosementioning

confidence: 99%

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

et al. 2019

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“…Although the pharmacokinetics of warfarin is similar in young and elderly adults, older patients have lower average weight, increasing their warfarin sensitivity, and also the prothrombin time ratio is increased, while adjusted to warfarin dose, suggesting increased pharmacodynamic effects as well . BMI influences the mean daily warfarin dose, although large interindividual variations exist within a BMI group . In our limited sample, with mean BMI only moderately elevated, no effect of BMI was observed on the warfarin dose requirement.…”

Section: Discussionmentioning

confidence: 52%

Warfarin dose requirement in patients having severe thrombosis or thrombophilia

Helin

Joutsi‐Korhonen

Asmundela

et al. 2019

Brit J Clinical Pharma

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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.430C>T, rs1799853), CYP2C9*3 (c.1075A>C, rs1057910) and VKORC1 c.-1639G>A (rs9923231) variants. The warfarin maintenance doses (target INR 2.0-3.0 in 94%, 2.5-3.5 in 6%) were estimated by the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) algorithms. The individual warfarin maintenance dose was tailored, supplementing estimates with comprehensive clinical evaluation and INR data.Results: Mean patient age was 47 years (range 20-76), and BMI 27 (SD 6), 68% being women. Forty-six (92%) had previous venous or arterial thrombosis, and 26 (52%) had a thrombophilia, with 22% having concurrent aspirin. A total of 40% carried the CYP2C9*2 or *3 allele and 54% carried the VKORC1-1639A allele. The daily mean maintenance dose of warfarin estimated by the Gage algorithm was 5.4 mg (95% CI 4.9-5.9 mg), and by the IWPC algorithm was 5.2 mg (95% CI 4.7-5.7 mg). The daily warfarin maintenance dose after clinical visits and follow-up was higher than the estimates, mean 6.9 mg (95% CI 5.6-8.2 mg, P < 0.006), with highest dose in patients having multiple thrombophilic factors (P < 0.03). Conclusions:In severe thrombosis and/or thrombophilia, variation in thrombin generation and pharmacodynamics influences warfarin response. Pharmacogenetic dosing algorithms seem to underestimate dose requirement.

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Section: Therapeutic Anticoagulation Prevalence Among Patients Of a Cmentioning

confidence: 64%

Therapeutic Anticoagulation Prevalence among Patients of a Cardiology Clinic receiving Warfarin and Association with Overweight

McKenzie¹,

Je²,

Procope³

et al. 2016

IJP

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The outcome of warfarin therapy varies among individuals due to factors such as genetics, age, ethnicity, diet and weight which have been shown to have varying impact on therapeutic anticoagulation [3-10]. Although many studies have reported benefits of the use of these parameters to determine warfarin doses, clinically guided management still relies heavily on monitoring International Normalized Ratio (INR). The primary objective of the study was to examine the prevalence of therapeutic anticoagulation with warfarin among patients registered in a setting where clinically guided management is the only available system for monitoring warfarin efficacy. The secondary objectives of the study include an assessment of the differences between subjects that are within the target INR range (therapeutic anticoagulation) and those subjects outside the target INR (non-therapeutic anticoagulation). Methods This was a cross-sectional, observational, convenience sample study of adults (at least 18 years of age) on warfarin maintenance therapy recruited from the University Hospital of the West Indies Cardiology Clinic in the two time periods (January 2014-May 2014 and February 2015-October 2015). Inclusion criteria also required subjects to be warfarin for more than one month and self-report of good compliance. Informed consent guidelines were followed and all subjects recruited in this study consented to participate. After Informed Consent was obtained, information recorded included daily dose, date of initiation, and indication for warfarin therapy. Also recorded for each subjects was age, weight, height, gender, ethnicity and concomitantly administered drugs. INR assessment A single sample of one drop (≥ 8µL) of capillary blood from each patient, obtained by pinprick was used to obtain INR

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Warfarin Dosing and Body Mass Index

Abstract: There is an association between BMI and the TWD of warfarin. This could have dosing implications for both patients and prescribers, as patients with a high BMI will be expected to require higher doses of warfarin to maintain a therapeutic INR.

Cited by 42 publications

References 28 publications

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

Warfarin dose requirement in patients having severe thrombosis or thrombophilia

Therapeutic Anticoagulation Prevalence among Patients of a Cardiology Clinic receiving Warfarin and Association with Overweight

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