Montes Ramón, Nantes Oscar, Alonso Alvaro, Zozaya José M, Hermida José
Haematology Department and the Division of Cardiovascular Sciences, Laboratory of Thrombosis and Haemostasis, Applied Medical Research Centre and Clinica Universitaria/School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
Br J Haematol. 2008 Dec;143(5):727-33. doi: 10.1111/j.1365-2141.2008.07414.x. Epub 2008 Oct 15.
The VKORC1 c.-1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4.19 (1.59-11.04)]; amiodarone use [adjusted OR (95% CI) = 9.97 (1.75-56.89)]; or aspirin use [adjusted OR (95% CI) = 8.97 (1.66-48.34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0.50 (0.26-0.99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.
维生素K环氧化物还原酶复合体1（VKORC1）基因c.-1639G>A多态性以及细胞色素P450 2C9（CYP2C9）基因c.430C>T和c.1075A>C多态性与口服抗凝剂敏感性增加有关。然而，它们在胃肠道出血中的作用尚不清楚。我们研究了与这些多态性相关的胃肠道出血风险，以及这种风险如何受到抗凝剂剂量和常用药物使用的影响。我们对89例接受醋硝香豆素治疗期间发生胃肠道出血的患者和177例接受醋硝香豆素治疗期间未发生出血的患者进行了研究。这三种多态性均未构成严重的胃肠道出血危险因素。然而，携带这些多态性中至少一种的患者在同时满足以下条件之一时处于高风险状态：醋硝香豆素每周剂量高于15 mg[校正比值比（OR）（95%置信区间（CI））=4.19（1.59 - 11.04）]；使用胺碘酮[校正OR（95%CI）=9.97（1.75 - 56.89）]；或使用阿司匹林[校正OR（95%CI）=8.97（1.66 - 48.34）]。他汀类药物的使用与较低的胃肠道出血风险相关[校正OR = 0.50（0.26 - 0.99）]。在接受醋硝香豆素治疗的患者中，若携带任何一种所研究的多态性，当每周醋硝香豆素剂量高于15 mg或使用胺碘酮或阿司匹林时，胃肠道出血风险会显著增加。
