年龄、CYP2C9基因分型及合并用药对华法林治疗前30天内凝血酶原时间上升速率的影响。
Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time during the first 30 days of warfarin therapy.
作者信息
Wilke Russell A, Berg Richard L, Vidaillet Humberto J, Caldwell Michael D, Burmester James K, Hillman Michael A
机构信息
Department of Internal Medicine, Marshfield Clinic, WI 54449, USA.
出版信息
Clin Med Res. 2005 Nov;3(4):207-13. doi: 10.3121/cmr.3.4.207.
OBJECTIVES
To characterize the impact of several important clinical variables on the rate of anticoagulation during warfarin initiation (i.e., the first 30 days).
DESIGN
Retrospective study.
SETTING
An anticoagulation service of a large horizontally integrated, multispecialty group practice in central and northern Wisconsin.
PARTICIPANTS
Patients with sufficient laboratory data obtained during the initiation phase of warfarin treatment.
METHODS
Patients were consented and genotyped for cytochrome P450 (CYP) 2C9 polymorphisms. Anticoagulation laboratory data were then electronically abstracted and fitted to a logistic growth model. Rate of anticoagulation was compared between groups.
RESULTS
During warfarin initiation, the mean slope for rise in International Normalized Ratio (INR) of prothrombin time was significantly associated with age (p = 0.03, n = 166). Because a relationship between diabetes and warfarin dosing has been suggested previously, we assessed the impact of this comorbidity in our model as well. Diabetes showed relatively little impact, but concomitant treatment with an anti-diabetic sulfonylurea medication was associated with an increase in slope (3-fold, p < 0.05). Since this drug interaction may occur at the level of CYP2C9, we also assessed the impact of CYP2C9 genotype in our model. The impact of CYP2C9 genotype was marginally significant (p = 0.119, non-pooled dataset; p = 0.053, data pooled for CYP2C9 *2/*2, *2/*3 and *3/*3).
CONCLUSIONS
Age and concomitant sulfonylurea therapy alter the rate of anticoagulation during the first 30 days of warfarin therapy.
目的
明确几种重要临床变量对华法林起始治疗阶段（即最初30天）抗凝速度的影响。
设计
回顾性研究。
地点
威斯康星州中部和北部一个大型横向整合的多专科集团诊所的抗凝服务部门。
参与者
在华法林治疗起始阶段获得充分实验室数据的患者。
方法
患者签署知情同意书并进行细胞色素P450（CYP）2C9基因多态性基因分型。然后对抗凝实验室数据进行电子提取并拟合到逻辑增长模型。比较各组之间的抗凝速度。
结果
在华法林起始治疗期间，凝血酶原时间国际标准化比值（INR）上升的平均斜率与年龄显著相关（p = 0.03，n = 166）。由于先前已表明糖尿病与华法林剂量之间存在关联，我们也在模型中评估了这种合并症的影响。糖尿病的影响相对较小，但同时使用抗糖尿病磺脲类药物与斜率增加有关（3倍，p < 0.05）。由于这种药物相互作用可能发生在CYP2C9水平，我们还在模型中评估了CYP2C9基因型的影响。CYP2C9基因型的影响略微显著（p = 0.119，非合并数据集；p = 0.053，合并CYP2C9 *2/*2、*2/3和3/*3的数据）。
结论
年龄和同时使用磺脲类疗法会改变华法林治疗最初30天的抗凝速度。
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