IWPC模型对下肢深静脉血栓形成患者华法林初始低强度抗凝疗效的影响

Influences of IWPC Model on the Initial Anticoagulation Response of Warfarin in Deep Venous Thrombosis Patients

目的:评价国际华法林药物基因组学联合会(IWPC)模型对下肢深静脉血栓形成患者(DVT)华法林初始抗凝疗效的影响。方法:100例DVT患者随机分为两组:研究组68例和对照组32例,均给予华法林抗凝治疗。研究组患者采用荧光染色原位杂交分析技术进行CYP2C9和VKORC1基因检测,利用IWPC模型计算华法林初始剂量,并根据国际标准化比值(INR)监测结果调整华法林至合适剂量;对照组直接根据INR监测结果调整华法林至合适剂量。比较两组患者在INR首次达标时间、INR达标维持时间、华法林抗凝治疗3、5、7天INR、INR达标率和INR总达标率、7天华法林累积剂量及治疗范围时间(TTR)的差异。结果:研究组患者CYP2C9 1075A>C基因以AA型为主(91.18%),C等位基因突变率5.15%,VKORC1 1639AA型79.41%,G等位基因携带率11.03%。研究组患者INR首次达标时间较对照组明显缩短(P<0.001),INR达标维持时间明显增加(P=0.02),华法林抗凝治疗3天INR及INR达标率明显高于对照组(P=0.01),且TTR为47.27%,较对照组29.01%明显增加(P<0.001)。结论:IWPC模型有助于提高下肢深静脉血栓形成患者华法林初始抗凝疗效,但其在华法林长期抗凝中的应用价值有待于临床进一步验证。

Objective:To assess the influences of IWPC model on initial anticoagulant therapy with warfarin in deep venous thrombosis (DVT).Methods:A total of 100 patients with DVT were randomly divided into the study group (68 cases) and the control group (32 cases).They received warfarin and the doses of warfarin were regulated to the proper maintain doses by the results of international normalized ratio (INR).All patients' CYP2C9 and VKORC1 genetic polymorphisms in the study group were detected by fluorescence in situ hybridization FISH and the initial dosages of warfarin were calculated by the IWPC model.The differences between the two groups were compared on the first time to target INR,the time of INR maintained in target,the INR and INR targeted rate in the third,fifth and seventh days of warfarin anticoagulation,the total INR targeted rate within seven days,the warfarin total doses within the first seven days and the time in therapeutic range (TTR).Results:In the study group,AA was 91.18% in CYP2C9 1075A>C with C allelic frequency at 5.15%,the VKORC1 1639AA was 79.41% with G allelic frequency at 11.03%.Compared with the control group,the study group showed shorter first time totarget INR (P<0.001),longer time of INR maintained in target (P=0.02) and higher INR and INR targeted rate in the third day (P=0.01).TTR in the study group was 47.27%,which was higher than that (29.01%) in the control group (P<0.001).Conclusion:The individualized medication based on CYP2C9 and VKORC1 gene detection can improve the initial anticoagulation response of warfarin in patients with deep venous thrombosis,but its value for long time needs further verification in clinic.