International Warfarin Genotype-Guided Dosing Algorithms in the Turkish Population and Their Preventive Effects on Major and Life-Threatening Hemorrhagic Events

Karaca, Sefayet; Bozkurt, Nujen Çolak; Cesuroğlu, Tomris; Karaca, Mehmet; Bozkurt, Mehmet Kürşat; Eskioğlu, Erdal; Polimanti, Renato

doi:10.2217/pgs.15.58

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…Results, comparable to our data, were demonstrated by the researchers Jaekyu Shin and Diana Cao of the Department of Clinical Pharmacy San Francisco -53.1 % (p = 0.071) [12]. Studies, conducted in the Turkish population, showed that the percentage within 20 % was 29 %, and MAE = 2.25 (SE = 0.23), which was significantly different from our results (p = 0.009) [14]. In the Asian population, we found that percentage within 20 % was 39.58 %, which was comparable with the data of Shin et al, for a sample of Asian patients -48.1 % (p = 0.33).…”

Section: Discussionsupporting

confidence: 58%

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Bairova

Самбялова

Rychkova

et al. 2019

Acta biomedica scientifica

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Background. To date, there are many pharmacogenetic algorithms for selecting the dose of warfarin. However, there is very little information about the predictive accuracy of the algorithms. We decided to evaluate the predictive accuracy of the Gage algorithm, using a calculator, located on the web site (http://www.warfarindosing.org) in two ethnic groups (Caucasians and Asians), living in Russia.Aim. To compare the actual warfarin dose (AWD) to the calculated warfarin dose (CWD), using the algorithm in two ethnic groups taking warfarin.Materials and methods. We included 114 patients (66 Caucasians and 48 Asians): the mean age was60.91 ± 12.34 years; 61 (53.51 %) men, and 53 (46.49 %) women. The comparative characteristics of the algorithm were tested using the mean absolute error (MAE) between AWD and CWD, and percentage of patients, whose CWD fell within 20 % of AWD (percentage within 20 %). Genotyping for CYP2C9*2, CYP2C9*3, CYP4F*2 and VKORC1 was performed by real-time polymerase chain reaction (RT-PCR) method using Pharmacogenetics Warfarin reagent kits (DNA technology, Russia).Results. The Gage algorithm produced the predictive accuracy with MAE = 1.02 ± 0.16 mg/day and percentage within 20 % for Asian patients was 39.6 %. We obtained MAE = 1.33 ± 0.16 mg/day and percentage within 20 % for Caucasian patients was 40.9 %. In two ethnic groups (Caucasians and Asians) of the Russian population, overall performance of warfarin pharmacogenetic dosing by the Gage algorithm was similar.Conclusions. Despite the performance limitation of the current warfarin pharmacogenetic dosing Gage algorithm, constant international normalized ratio monitoring is important.

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Section: Discussionsupporting

confidence: 58%

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Bairova

Самбялова

Rychkova

et al. 2019

Acta biomedica scientifica

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“…This study contributed to understanding the genetics of asthma- and allergy-related phenotypes in non-European individuals in order to reduce health disparities among human populations. Indeed, the Turkish population is an admixture of European, Middle Eastern, and Central Asian ancestries and previous studies have confirmed that genetics contributes to the epidemiological differences observed between Turkish and European subjects 16 17 18 19 . In particular, comparing Turkish and European populations, we identified functional haplotype diversity of the immunogenes investigated between Turkish and northern/western European populations 20 .…”

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confidence: 76%

Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children

Karaca

Civelek

Karaca

et al. 2016

Sci Rep

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To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests. Multiple associations were observed for ADAM33: rs2280090 was associated with reduced MEF240% (i.e., the ratio of Mean Expiratory Flow after 240s of hypertonic saline inhalation with respect to the age- and ancestry-matched reference value) and with an increased risk of allergic bronchitis (p = 1.77*10−4 and p = 7.94*10−4, respectively); rs3918396 was associated with wheezing and eczema comorbidity (p = 3.41*10−4). IL4 rs2243250 was associated with increased FEV240 (Forced Expiratory Flow Volume after 240s of hypertonic saline inhalation; p = 4.81*10−4) and CD14 rs2569190 was associated with asthma diagnosis (p = 1.36*10−3). ADAM33 and IL4 appeared to play a role in the processes linked to allergic airway inflammation and lung function. Due to its association with wheezing and eczema comorbidity, ADAM33 may also be involved in the atopic march.

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“…Operational definitions (adapted from references). 7,8,11,12,14,15 Actual warfarin dose: is the maintenance dosing that is taken by the patient. 11,12,14 Warfarin 5 mg fixed standard dose: it is the strategy to initiate warfarin therapy by given 5 mg dose then after 3 days can be adjusted according to INR.…”

Section: Discussionmentioning

confidence: 99%

“…7 In order to apply a developed clinical algorithm in practice, the algorithm must first be validated in terms of accuracy, practicality and safety. 1,12 The rationale of the current study, relies on the fact that warfarin is used widely in our population despite the known pharmacokinetic and pharmacodynamics problems including adverse effects and hospitalization due to bleeding. There is a growing trend for using the direct oral anticoagulants (DOAC), nevertheless the cost resembles a major barrier for their continued use.…”

Section: Introductionmentioning

confidence: 99%

Validation and comparison between two warfarin dosing clinical algorithms and warfarin fixed dosing in specialized heart center: cross-sectional study

Elnour¹,

Ahmed²,

Khalid³

et al. 2022

PHARMPRACT

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Background: Warfarin is well known as a narrow therapeutic index that has prodigious variability in response which challenges dosing adjustment for the maintenance of therapeutic international normalized ratio. However, an appreciated population not on new oral anticoagulants may still need to be stabilized with warfarin dosing. Objective: The current study's main objective was to validate and compare two models of warfarin clinical algorithm models namely the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) with warfarin 5 mg fixed standard dosing strategy in a sample of Sudanese subjects. Method: We have conducted a cross-sectional study recruited from the out-patient clinic at a tertiary specialized heart center. We included subjects with unchanged warfarin dose (stabilized), and with therapeutic international normalized ratio. The predicted doses of warfarin in the two models were calculated by three different methods (accuracy, clinical practicality, and the clinical safety of the clinical algorithms). Main outcome measure: The primary outcomes were the measurements of the clinical (accuracy, practicality, and safety) in each of the two clinical algorithms models compared to warfarin 5 mg fixed standard dose strategy. Results: We have enrolled 71 Sudanese subjects with mean age (51.7 ± 14 years), of which (49, 69.0%) were females. There was no significant difference between the warfarin 5 mg fixed standard dose strategy and the predicted doses of the two clinical algorithm models (MAE 1.44, 1.45, and 1.49 mg/day [P =0.4]) respectively. In the clinical practicality, all of the three models had a high percent of subjects (95.0%, 51.9%, and 66.7%) in the ideal dose range in middle dose group (3-7 mg/ day) for warfarin 5 mg fixed standard dosing strategy, Gage, and IWPC clinical algorithm models respectively. However, a small percent of subjects was exhibited in the warfarin low dose group ≤ 3 mg/day (0.0%, 15.0%, and 10.0%) and warfarin high dose group ≥ 7 mg/day (0.0%, 33.3%, and 33.3%) for warfarin 5 mg fixed standard dosing strategy, Gage, and IWPC clinical algorithms respectively. In terms of clinical safety, the percent of subjects with severely over-prediction were 28.2%, 22.5%, and 22.5% for warfarin 5 mg fixed standard dosing, Gage, and IWPC, respectively. While the percent of severely under-prediction was 12.7%, 7.0%, and 5.6% for the warfarin 5 mg fixed standard dosing, Gage, and IWPC, respectively. Conclusion: The Gage and IWPC clinical algorithm models were accurate, more clinically practical, and clinically safe than warfarin 5 mg standard dosing in the study population. The cardiologist can use either models (Gage and IWPC) to stratify subjects for accurate, practical, and clinically safe warfarin dosing..

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International Warfarin Genotype-Guided Dosing Algorithms in the Turkish Population and Their Preventive Effects on Major and Life-Threatening Hemorrhagic Events

Abstract: Although genetic information can predict the therapeutic warfarin dose, the accuracy of the international pharmacogenetic algorithms is not sufficient to be used for warfarin screening in Turkish patients.

Cited by 13 publications

References 40 publications

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children

Validation and comparison between two warfarin dosing clinical algorithms and warfarin fixed dosing in specialized heart center: cross-sectional study

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