Warfarin dose requirement in patients having severe thrombosis or thrombophilia

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http://hdl.handle.net/10138/313832

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Helin , T A , Joutsi-Korhonen , L , Asmundela , H , Niemi , M , Orpana , A & Lassila , R 2019 , ' Warfarin dose requirement in patients having severe thrombosis or thrombophilia ' , British Journal of Clinical Pharmacology , vol. 85 , no. 8 , pp. 1684-1691 . https://doi.org/10.1111/bcp.13948

Title: Warfarin dose requirement in patients having severe thrombosis or thrombophilia
Author: Helin, Tuukka A.; Joutsi-Korhonen, Lotta; Asmundela, Heidi; Niemi, Mikko; Orpana, Arto; Lassila, Riitta
Contributor: University of Helsinki, HUSLAB
University of Helsinki, Department of Clinical Chemistry and Hematology
University of Helsinki, Hematologian yksikkö
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, HUS Comprehensive Cancer Center
Date: 2019-08
Language: eng
Number of pages: 8
Belongs to series: British Journal of Clinical Pharmacology
ISSN: 0306-5251
URI: http://hdl.handle.net/10138/313832
Abstract: 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.
Subject: dosing algorithm
thrombophilia
thrombosis
VKORC1
warfarin
INTERNATIONAL NORMALIZED RATIO
ANTICOAGULATION CONTROL
VENOUS THROMBOEMBOLISM
GENOTYPE
RISK
GENERATION
ANTITHROMBIN
POLYMORPHISM
ALGORITHM
317 Pharmacy
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