凝血酶生成试验在监测华法林抗凝治疗中的应用

The application of thrombin generation tests to warfarin anticoagulation monitoring

目的探讨不同抗凝强度口服华法林治疗患者的凝血酶生成情况及其与出血的关系以及凝血酶生成试验在监测华法林抗凝治疗中的应用。方法采集78例因心脏瓣膜置换术后房颤而口服华法林3个月以上的患者血样，检测凝血酶原时间一国际正常化比值（PT—INR）及凝血酶生成状况。结果华法林治疗组按PT—INR不同分成三组：Ⅰ组23例，PT—INR为1．51～2．00；Ⅱ组39例，PT—INR为2．01～3．00；Ⅲ组16例，PT—INR为3．01～4．26。三组凝血酶生成的延迟时间（lagtime）、峰值（peak）、达峰时间（ttpeak）都存在显著性差异（P〈0．01），而反映凝血酶总体生成量的指标凝血酶生成潜力（endogenous thrombin potential，ETP），Ⅰ组和Ⅱ组比较差异存在统计学意义（P=0．0001），Ⅱ组和Ⅲ组比较差异无统计学意义（P=0．06）。有出血并发症的患者5例，其ETP值小于正常对照组的15％。结论口服华法林抗凝治疗患者，当PT—INR〉3．0后，提高剂量会增加出血风险，但并不降低凝血酶生成量。服用华法林抗凝治疗期间同时检测PT—INR和ETP能更好地反映机体的凝血状态，从而有效地防止出血发生。

Objectives To explore the thrombin generation capacity in patients on warfarin therapy with different prothrombin time international normalized ratio （PT-INR）, the capacity in relation to bleeding, and the application of thrombin generation tests to warfarin therapy monitoring. Methods Seventy eight blood samples were taken from patients on warfarin therapy for more than 3 months owing to valve replacement or atrial fibrillation. The patients＇ case history and PT-INR were collected and thrombin generation tests were performed in all samples. Results Patients were ranked into three groups according to different PT-INR. There were 23 patients in group Ⅰ with PT-INR from 1.51 to 2.00, 39 patients in group Ⅱ with PT-INR from 2.01 to 3.00, and 16 patients in group Ⅲ with PT-INR from 3.01 to 4.26. There were significant differences between each two of the three groups in lagtime, peak, and ttpeak（ time to peak） （ P 〈 0.01 ）. There was a significant difference between group Ⅰ and group Ⅱ in endogenous thrombin potential （ETP） （ P = 0. 0001 ） , but not between group Ⅱ and grpup Ⅲ （ P = 0.06）. Five patients developed bleeding and their ETP was less than 15% of normal control. Conclusion In patients on warfarin therapy, when the PT-INR was more than 3.0, increasing the dose of warfarin doesn＇ t decrease the thrombin generation, but increase bleeding risk. PT-INR combined with ETP may better reflect patient＇ s coagulation status, therefore be of more significance in preventing bleeding.