The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation
The aim. To investigate the influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation (AF) during the year. Materials and methods. The study involved 60 patients with AF, age 70.50 (64.25; 76.25) years (32 men and 28 women)....
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| Format: | Article |
| Language: | English |
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Zaporozhye State Medical University
2022-06-01
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| Series: | Patologìâ |
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| Online Access: | http://pat.zsmu.edu.ua/article/view/252662/254970 |
| _version_ | 1811239875728375808 |
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| author | Ya. M. Mykhailovskyi |
| author_facet | Ya. M. Mykhailovskyi |
| author_sort | Ya. M. Mykhailovskyi |
| collection | DOAJ |
| description | The aim. To investigate the influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation (AF) during the year.
Materials and methods. The study involved 60 patients with AF, age 70.50 (64.25; 76.25) years (32 men and 28 women). Coagulogram indexes with International Normalized Ratio (INR) were determined using Coag Chrome 3003 monthly; the CHA2DS2-VASC, HAS-BLED, SAMe-TT2R2 scales scores were evaluated; the calculation of TTR was performed using the Rosendaal method. CYP2C9, CYP4F2, VKORC1 genes polymorphisms were determined using multiplex real time polymerase chain reaction in CFX-96 thermocycler (BioRad).
Results. Median TTR in groups of patients with SAMe-TT2R2 score <2 (n = 33) and ≥2 (n = 27) did not differ significantly (74 % versus 68 % respectively, P > 0.05). There were significantly more patients with TTR <70 % in the group with predicted labile INR (59.36 % versus 30.30 %; χ2 = 5.07, P < 0.05). SAMe-TT2R2 score ≥2 increased the risk of poor INR control by 1.96 times (CI 1.05–3.63). No association of TTR with CYP2C9, CYP4F2 and VKORC1 gene polymorphisms was found.
Episodes of excessive hypocoagulation (INR >4) were detected in 21 (40 %) patients during the year. Excessive hypocoagulation was significantly more common in patients carrying the allele A of the VKORC1 gene in comparison with non-carriers (51.43 % versus 24.00 %; χ2 = 4.57, P < 0.05). The presence of mutant allele A was associated with 2.14-fold higher risk of excessive hypocoagulation (RR = 2.14; CI 1.06–4.69).
Taking amiodarone (χ2 = 3.13; P < 0.05) had a significant effect on the development of excessive hypocoagulation with a relative risk RR = 1.83 (CI 1.01–3.35).
Conclusions. SAMe-TT2R2 score can be useful to predict poor INR control, while VKORC1 genotype estimating – to predict excessive hypocoagulation episodes. An integrated approach using clinical and genetic methods is needed to determine the potential efficacy and safety of warfarin therapy. |
| first_indexed | 2024-04-12T13:08:55Z |
| format | Article |
| id | doaj.art-0c6ace18844a4783bd0fe90a5c48a1f7 |
| institution | Directory Open Access Journal |
| issn | 2306-8027 2310-1237 |
| language | English |
| last_indexed | 2024-04-12T13:08:55Z |
| publishDate | 2022-06-01 |
| publisher | Zaporozhye State Medical University |
| record_format | Article |
| series | Patologìâ |
| spelling | doaj.art-0c6ace18844a4783bd0fe90a5c48a1f72022-12-22T03:31:55ZengZaporozhye State Medical UniversityPatologìâ2306-80272310-12372022-06-01191121710.14739/2310-1237.2022.1.252662The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillationYa. M. Mykhailovskyi0https://orcid.org/0000-0002-1310-8585Zaporizhzhia State Medical University, Ukraine, UkraineThe aim. To investigate the influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation (AF) during the year. Materials and methods. The study involved 60 patients with AF, age 70.50 (64.25; 76.25) years (32 men and 28 women). Coagulogram indexes with International Normalized Ratio (INR) were determined using Coag Chrome 3003 monthly; the CHA2DS2-VASC, HAS-BLED, SAMe-TT2R2 scales scores were evaluated; the calculation of TTR was performed using the Rosendaal method. CYP2C9, CYP4F2, VKORC1 genes polymorphisms were determined using multiplex real time polymerase chain reaction in CFX-96 thermocycler (BioRad). Results. Median TTR in groups of patients with SAMe-TT2R2 score <2 (n = 33) and ≥2 (n = 27) did not differ significantly (74 % versus 68 % respectively, P > 0.05). There were significantly more patients with TTR <70 % in the group with predicted labile INR (59.36 % versus 30.30 %; χ2 = 5.07, P < 0.05). SAMe-TT2R2 score ≥2 increased the risk of poor INR control by 1.96 times (CI 1.05–3.63). No association of TTR with CYP2C9, CYP4F2 and VKORC1 gene polymorphisms was found. Episodes of excessive hypocoagulation (INR >4) were detected in 21 (40 %) patients during the year. Excessive hypocoagulation was significantly more common in patients carrying the allele A of the VKORC1 gene in comparison with non-carriers (51.43 % versus 24.00 %; χ2 = 4.57, P < 0.05). The presence of mutant allele A was associated with 2.14-fold higher risk of excessive hypocoagulation (RR = 2.14; CI 1.06–4.69). Taking amiodarone (χ2 = 3.13; P < 0.05) had a significant effect on the development of excessive hypocoagulation with a relative risk RR = 1.83 (CI 1.01–3.35). Conclusions. SAMe-TT2R2 score can be useful to predict poor INR control, while VKORC1 genotype estimating – to predict excessive hypocoagulation episodes. An integrated approach using clinical and genetic methods is needed to determine the potential efficacy and safety of warfarin therapy.http://pat.zsmu.edu.ua/article/view/252662/254970atrial fibrillationwarfarincyp2c9cyp4f2vkorc1polymorphismgenessame-tt2r2anticoagulation stability |
| spellingShingle | Ya. M. Mykhailovskyi The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation Patologìâ atrial fibrillation warfarin cyp2c9 cyp4f2 vkorc1 polymorphism genes same-tt2r2 anticoagulation stability |
| title | The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation |
| title_full | The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation |
| title_fullStr | The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation |
| title_full_unstemmed | The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation |
| title_short | The influence of clinical and genetic factors on the stability of warfarin’s anticoagulant effect in patients with atrial fibrillation |
| title_sort | influence of clinical and genetic factors on the stability of warfarin s anticoagulant effect in patients with atrial fibrillation |
| topic | atrial fibrillation warfarin cyp2c9 cyp4f2 vkorc1 polymorphism genes same-tt2r2 anticoagulation stability |
| url | http://pat.zsmu.edu.ua/article/view/252662/254970 |
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