诊断学理论与实践

诊断学理论与实践 ›› 2020, Vol. 19 ›› Issue (04): 370-374.doi: 10.16150/j.1671-2870.2020.04.009

• 论著 • 上一篇    下一篇

凝血酶生成试验在预测血管性血友病患者出血倾向中的作用

梁茜a, 陆峥菁b, 邵妍妍a, 丁秋兰a, 王鸿利b, 王学锋a()   

  1. 上海交通大学医学院附属瑞金医院a. 检验科；b. 医学基因组国家重点实验室上海血液学研究所,上海 200025
  • 收稿日期:2020-01-04 出版日期:2020-08-25 发布日期:2022-07-15
  • 通讯作者: 王学锋 E-mail:wangxuefeng6336@hotmail.com
  • 基金资助:
    2017广慈卓越青年C计划;2018上海市“医苑新星”青年医学人才类——临床检验项目

The application of thrombin generation test for assessing hemorrhagic tendency in patients with von Willebrand disease

LIANG Qiana, LU Zhengjingb, SHAO Yanyana, DING Qiulana, WANG Honglib, WANG Xuefenga()   

  1. a. Department of Laboratory Medicine, b. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2020-01-04 Online:2020-08-25 Published:2022-07-15
  • Contact: WANG Xuefeng E-mail:wangxuefeng6336@hotmail.com

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摘要：

目的： 评估凝血酶生成试验（thrombin generation test, TGT）在预测血管性血友病（von Willebrand disease, vWD）患者出血倾向中的应用价值。方法： 选取2018年1月至2019年7月就诊于上海交通大学医学院附属瑞金医院的vWD患者38例,并根据出血严重程度分为轻度出血组（包括8例1型患者）、中度出血组（包括8例2A型和6例2M型患者）和重度出血组（包括2例2N型、6例重型1型和8例3型患者）。另选同期相同年龄段的5名健康体检者作为正常对照组。采集乏血小板血浆,分别检测患者与正常对照者间在1 pmol/L组织因子（tissue factor, TF）和5 pmol/L TF试剂激活下的凝血酶生成能力的差异,并分析TGT各参数[凝血酶生成峰值（以下简称峰值）、凝血酶生成潜力（endogenous thrombin potential, ETP）、达峰时间（time to peak, ttPeak）等]与患者血浆血管性血友病因子（von Willebrand factor,vWF）抗原（vWF∶Ag）水平、vWF活性水平（vWF∶Act）及凝血因子Ⅷ活性（FⅧ∶C）间的相关性。结果： 在1 pmol/L TF激活下,正常对照组的峰值显著高于轻度出血组、中度出血组及重度出血组（P<0.05）,重度出血组的峰值显著低于轻度出血组及中度出血组（P均<0.01）,ETP和ttPeak仅在重度出血组与其余各组间差异有统计学意义（P均<0.01）。在5 pmol/L TF激活下,各组间峰值差异缩小,且正常对照组与轻度出血患者组的峰值间差异无统计学意义（P>0.05）,ETP、ttPeak值在各组间差异均无统计学意义（P>0.05）。此外,在1 pmol/L TF激活下的峰值与患者FⅧ:C间的相关性最好（相关系数R2为0.65）;在1 pmol/L、5 pmol/L TF激活下,TGT参数（ETP和ttPeak）与患者vWF∶Ag、vWF∶Act间的相关性较弱（R2<0.5）。结论： 1 pmol/L TF激活下TGT参数的峰值可较好地反映不同出血严重程度vWD患者的出血倾向。

关键词: 血管性血友病, 凝血酶生成试验, 出血倾向

Abstract:

Objective: To assess the value of thrombin generation test (TGT) for predicting hemorrhagic tendencyin patients with von Willebr and disease (vWD). Methods: A total of 38 vWD patients from Shanghai Ruijin Hospital during January 2018 to July 2019 were enrolled, and were divided into three groups: mild bleeding group (8 mild bleeders, type 1 patients), moderate bleeding group (14 moderate bleeders, including 8 type 2A patients and 6 type 2M patients) and severe bleeding group (16 severe bleeders, including 2 type 2N patients, 6 severe type 1 patients and 8 type 3 patients). Five healthy subjects in the same age were served as the control group. Platelet-poor plasma samples were prepared by centrifugation. The difference in thrombin-generating capacity between patients and controls were tested by TGT, which was activated with 1 pmol/L tissue factor(TF) and 5 pmol/L TF, respectively. The correlations of vWF∶Ag, vWF∶Act, FⅧ∶C with TGT parameters [Peak value, endogenous thrombin potential (ETP), time to peak (ttPeak)] were also studied. Results: Under 1 pmol/L TF activation, the Peak value of TGT in controls was significantly higher than those in mild, moderate and severe bleeders (P<0.000 1), and the Peak value in severe bleeders was significantly lower than those in mild and moderate cases. (P=0.000 1). Furthermore, ETP and ttPeakvalues showed significant difference between severe bleeding group and the other groups. While TGT was activated with 5 pmol/L TF, the difference in TGT parameters decreased between groups. There was no significant difference in Peak values between controls and mild bleeders, and ETP and ttPeakvaluesdid not differ significantly between the groups (P>0.05). In addition, FVIII∶C levels had a good correlation with Peak values measured at 1 pmol/L TF activation (R2=0.65), whilev WF∶Ag and vWF∶Act were weakly correlated with any of TGT parameters at 1 pmol/L or 5 pmol/LTF activation (R2<0.50). Conclusions: Activated with 1 pmol/L TF, Peak value of TGT may serve as a useful laboratory tool to evaluate thehemorrhagic tendency in different types of vWD.

Key words: von Willebrand disease, Thrombin generation test, Hemorrhagic tendency

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