Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HE Fan ^1,2 , REN Rong ¹ , LIU Guanjian ³ , DENG Yundan ¹ , LIN Fushun ¹ ,  XIAO Xijun ¹

1. Division of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. Heart Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310020, P.R.China;
3. Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

XIAO Xijun, Email: xijunxiao@hotmail.com

Keywords：

Mechanical valve replacement; early anticoagulation; warfarin dose; influence factors

DOI：

10.7507/1007-4848.201503029

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Objective Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement were analyzed to guide the anticoagulation therapy for these patients. Methods A total of 288 patients within 6 months after mechanical prosthetic valve replacement in West China Hospital were followed up and registered at outpatient department from July 2012 to April 2014, including basic information (name, sex, age, height, weight, etc.), general clinical data (cardiac function, heart rate, surgery pattern, etc.) and related data about anticoagulation therapy. The target international standardized ratio (INR) range was 1.60 to 2.20 and the acceptable INR was 1.50 to 2.30. The sex, age, height, body weight, body mass index (BMI), body surface area (BSA) and related clinical factors were analyzed to find the relationship with the dose of warfarin. Results Sex was found to have a significant effect on the stable warfarin dose (P<0.05). Women needed a lower stable warfarin dose than men during the early anticoagulation therapy. There was no significant difference in the stable warfarin dose of patients with different ages, rhythms, NYHA classification, surgery pattern and diseases before operation; but the stable warfarin dose was lower in the patients with radiofrequency ablation during valve replacement procedures than the patients with single valve replacement (P<0.05). There was an association between age, height, weight, BMI, BSA and the stable warfarin dose withR² of 1.2%, 3.2%, 3.5%, 1.1%, 4.2%, respectively and they could explain 6.1% of variability in warfarin dose. Conclusion During early anticoagulation therapy in patients with mechanical prosthetic valve replacement, it is necessary to consider the effects of various preoperative factors, drug factors and demographic factors on warfarin dose. Even though there is an association between age, height, weight, BMI, BSA and the stable warfarin dose, which can only explain 6.1% of variability in warfarin dose, thus cannot guide the postoperative anticoagulation of these patients.

Citation： HE Fan, REN Rong, LIU Guanjian, DENG Yundan, LIN Fushun, XIAO Xijun. Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(5): 363-368. doi: 10.7507/1007-4848.201503029 Copy

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2.	Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J, 2007, 7(2): 99-111.
3.	郑策, 梅丹. 影响华法林抗凝血作用的有关因素. 药物不良反应杂志, 2007. 9(4): 256-261.
4.	胡咏梅, 王雨若. 关于中国人体表面积公式的研究. 生理学报, 1999. 51(1): 45-48.
5.	刘寅强. 心脏瓣膜置换术后华法林个体化抗凝研究. 昆明: 昆明医科大学. 2013.
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7.	Takahashi H, Echizen H. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics J, 2003, 3(4): 202-214.
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11.	张松波, 周宏灏. 药物代谢性别差异及与核受体的关系. 中国药理学通报, 2007, 23(3): 292-294.
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13.	Mueller JA, Patel T, Halawa A, et al. Warfarin dosing and body mass index. Ann Pharmacother, 2014, 48(5): 584-588.
14.	Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis, 2013, 36(1): 96-101.
15.	Gage BF, Fihn SD, White RH. Management and dosing of warfarin therapy. Am J Med, 2000, 109(6): 481-488.
16.	Gage BF, Eby C, Milligan PE, et al. Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost, 2004, 91(1): 87-94.
17.	Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 2001, 119(1 suppl): 8S-21S.
18.	Haber LT, Maier A, Gentry PR, et al. Genetic polymorphisms in assessing interindividual variability in delivered dose. Regul Toxicol Pharmacol, 2002, 35(2): 177-197.
19.	Sconce EA, Khan TI, Wynne HA, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 2005, 106(7): 2329-2333.
20.	Voora D, Eby C, Linder MW, et al. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb Haemost, 2005, 93(4): 700-705.
21.	Miao L, Yang J, Huang C, et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. Eur J Clin pharmacol, 2007, 63(12): 1135-1141.
22.	曹浩, 葛建军, 周汝元, 等. 心脏瓣膜置换术后早期抗凝影响因素分析. 山东医药, 2007, 46(33): 25-26.
23.	Naganuma M, Shiga T, Nishikata K, et al. Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther, 2001, 6(4): 363-367.
24.	Hirsh J, Fuster V, Ansell J, et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol, 2003, 41(9): 1633-1652.

1. Khoury G, Sheikh-Taha M. Effect of age and sex on warfarin dosing. Clinical pharmacology: advances and applications. Clin Pharmacol, 2014, 6: 103.
2. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J, 2007, 7(2): 99-111.
3. 郑策, 梅丹. 影响华法林抗凝血作用的有关因素. 药物不良反应杂志, 2007. 9(4): 256-261.
4. 胡咏梅, 王雨若. 关于中国人体表面积公式的研究. 生理学报, 1999. 51(1): 45-48.
5. 刘寅强. 心脏瓣膜置换术后华法林个体化抗凝研究. 昆明: 昆明医科大学. 2013.
6. Loebstein R, Yonath H, Peleg D, et al. Interindividual variability in sensitivity to warfarin-Nature or nurture? Clin Pharm Ther, 2001, 70(2): 159-164.
7. Takahashi H, Echizen H. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics J, 2003, 3(4): 202-214.
8. Absher RK, Moore ME, Parker MH. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacother, 2002, 36(10): 1512-1517.
9. Gan GG, Teh A, Goh KY, et al. Racial background is a determinant factor in the maintenance dosage of warfarin. Intern J Hematol, 2003, 78(1): 84-86.
10. Casner PR, Sandoval E. Increased sensitivity to warfarin in elderly Hispanics. J Clin Pharmacol, 2002, 42(2): 145-150.
11. 张松波, 周宏灏. 药物代谢性别差异及与核受体的关系. 中国药理学通报, 2007, 23(3): 292-294.
12. Crooks J, Omalley K, Stevenson IH. Pharmacokinetics in the elderly. Clin Pharmacokinet 1976, 1: 280-296.
13. Mueller JA, Patel T, Halawa A, et al. Warfarin dosing and body mass index. Ann Pharmacother, 2014, 48(5): 584-588.
14. Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis, 2013, 36(1): 96-101.
15. Gage BF, Fihn SD, White RH. Management and dosing of warfarin therapy. Am J Med, 2000, 109(6): 481-488.
16. Gage BF, Eby C, Milligan PE, et al. Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost, 2004, 91(1): 87-94.
17. Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 2001, 119(1 suppl): 8S-21S.
18. Haber LT, Maier A, Gentry PR, et al. Genetic polymorphisms in assessing interindividual variability in delivered dose. Regul Toxicol Pharmacol, 2002, 35(2): 177-197.
19. Sconce EA, Khan TI, Wynne HA, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 2005, 106(7): 2329-2333.
20. Voora D, Eby C, Linder MW, et al. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb Haemost, 2005, 93(4): 700-705.
21. Miao L, Yang J, Huang C, et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. Eur J Clin pharmacol, 2007, 63(12): 1135-1141.
22. 曹浩, 葛建军, 周汝元, 等. 心脏瓣膜置换术后早期抗凝影响因素分析. 山东医药, 2007, 46(33): 25-26.
23. Naganuma M, Shiga T, Nishikata K, et al. Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther, 2001, 6(4): 363-367.
24. Hirsh J, Fuster V, Ansell J, et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol, 2003, 41(9): 1633-1652.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement

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