华法林抗凝治疗患者维生素K依赖性凝血因子、蛋白C及蛋白S活性改变的分析

doi:10.16150/j.1671-2870.2022.03.012

摘要/Abstract

摘要：

目的：探讨华法林抗凝治疗对维生素K依赖的凝血因子[凝血因子Ⅱ（coagulation factors Ⅱ, FⅡ）、FⅦ、FⅨ、FⅩ]及抗凝系统中蛋白C（protein C, PC）及蛋白S（protein S, PS）活性的下调作用,以及对抗凝促凝平衡的影响。方法：收集2018年1月至2020年3月在我院接受华法林抗凝治疗的肺栓塞患者和深静脉血栓患者,检测其FⅡ、FⅦ、FⅨ、FⅩ、PC及PS活性,分析其与凝血酶原时间（prothrombin time, PT）/国际标准化比值（international standardized ratio, INR）间的相关性;并参照INR进行四分位法分组,比较各组间凝血及抗凝因子活性水平的差异。结果：除PS活性外,不同INR四分位组间所对应的各因子活性水平差异均存在统计学意义（FⅡ、FⅦ、FⅩ,P<0.000 1;PC,P<0.001;FⅨ,P<0.05）。患者的INR（1.32~5.85）与FⅡ、FⅦ、FⅨ、FⅩ及PC活性呈负相关（r分别为-0.678 7、-0.692 6、-0.376 7、-0.595 4及-0.466 6）,但与PS活性间的相关性较弱（r为-0.212 2）。相较于抗凝蛋白PC及PS,华法林抑制的维生素K依赖的羧基化对凝血因子活性和表达的影响更为显著,凝血因子活性与抗凝蛋白活性的比值随INR升高而降低。结论：华法林虽然同时干扰维生素K依赖性凝血因子及抗凝蛋白PC、PS的羧基化,降低其活性,但对凝血因子的抑制更为显著。在使用华法林治疗时对抗凝和凝血因子进行检测,将有助于对患者的精准诊断和治疗。

关键词: 华法林, 国际标准化比值, 凝血因子活性, 蛋白C活性, 蛋白S活性

Abstract:

Objective: To investigate the effects of warfarin anticoagulant therapy on vitamin K dependent clotting factors and down-regulation of protein C and protein S activities in anticoagulant system, as well as the effects of changes in above indic on anticoagulant balance. Methods: A total of 57 patients with pulmonary embolism or deep venous thrombosis treated with warfarin anticoagulant therapy in our hospital from January 2018 to March 2020 were enrolled, and activities of coagulation factors FⅡ, FⅦ, FⅨ, FⅩ, PC and PS were detected. International standardized ratio(INR) wasgrouped by quartile and the differences in the activity levels of coagulant and anticoagulant factors, protein C and protein S activities between 4 groups were compared. Results: There were statistically significant differences in the activity levels of each factor between different INR quartile groups (FⅡ, FⅦ, FⅩ: P<0.000 1; PC: P<0.001; FⅨ P<0.05). However, there was no significant difference in PS activity among different INR quartile groups(INR: 1.32-5.85), and INR level was negatively correlated with the activity of FⅡ, FⅦ, FⅨ, FⅩ, PC and PS (r was -0.678 7, -0.692 6, -0.376 7, -0.595 4, -0.466 6, and -0.212 2 respectively). The ratio of coagulation factor activity to anticoagulant protein activity decreased with the increase of INR. Conclusions: Although warfarin also interferes with carboxylation of vitamin K dependent clotting factors and anticoagulant proteins PC and PS, and decreasing their activity, clotting factors are affected more significantly.

Key words: Warfarin, International standardized ratio, Coagulation factor activity, Protein C activity, Protein S activity

中图分类号:

R554

范臻佳, 刘禹, 许冠群, 武文漫, 王学锋. 华法林抗凝治疗患者维生素K依赖性凝血因子、蛋白C及蛋白S活性改变的分析[J]. 诊断学理论与实践, 2022, 21(03): 362-366.

FAN Zhenjia, LIU Yu, XU Guanqun, WU Wenman, WANG Xuefeng. The analysis of activities of vitamin K-dependent coagulation factors, protein C and protein S in patients on warfarin therapy[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(03): 362-366.

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项目	男	女
血栓发生部位
肺栓塞	19	8
下肢深静脉血栓	21	9
血栓发生的原因
PC缺陷症	8	3
PS缺陷症	5	2
抗凝血酶缺陷症	5	2
其他类型	21	11

比值	Q1组（n=14）	Q2组（n=18）	Q3组（n=12）	Q4组（n=13）	r	P值
PC/FⅡ	1.12（0.53~3.33）	1.93（0.97~2.83）	2.34（0.60~4.27）	2.34（0.91~4.15）	0.432 3	0.000 8
PC/FⅦ	1.67（0.60~3.58）	2.71（1.20~4.48）	2.99（1.78~10.43）	6.20（1.19~17.27）	0.604 0	<0.000 1
PC/FⅨ	1.02（0.25~2.09）	1.10（0.49~3.16）	1.22（0.29~2.24）	1.00（0.26~4.41）	0.083 38	0.537 5
PC/FⅩ	1.66（0.49~3.27）	2.77（0.93~4.80）	2.63（0.93~6.08）	2.86（1.03~5.54）	0.290 8	0.028 2
PS/FⅡ	1.55（0.67~3.63）	1.76（0.51~2.80）	2.45（0.98~3.66）	2.87（2.22~6.95）	0.725 7	<0.000 1
PS/FⅦ	1.65（0.74~5.30）	2.05（0.55~7.83）	3.15（1.58~21.09）	5.50（2.19~31.55）	0.590 3	<0.000 1
PS/FⅨ	0.85（0.38~2.28）	0.95（0.16~2.29）	1.06（0.55~1.81）	1.27（0.70~3.45）	0.397 6	0.002 2
PS/FⅩ	1.63（1.03~3.56）	2.17（0.63~3.87）	2.60（1.44~4.61）	3.55（2.17~7.53）	0.658 1	<0.000 1