Zwaveling Suzanne, Bloemen Saartje, de Laat Bas, Ten Cate Hugo, Ten Cate-Hoek Arina
Laboratory for Clinical Thrombosis and Hemostasis, Internal Medicine and Biochemistry, Maastricht University, Maastricht, The Netherlands.
Synapse Research Institute, Maastricht, The Netherlands.
TH Open. 2018 Sep 26;2(3):e291-e302. doi: 10.1055/s-0038-1672183. eCollection 2018 Jul.
Bleeding is a feared adverse event during anticoagulant treatment. In patients on vitamin K antagonists, most bleedings occur with the international normalized ratio (INR) in the therapeutic range. Currently, identification of high-risk patients via laboratory methods is not reliable. In this systematic review, we assessed the ability of calibrated automated thrombin generation (CAT-TG) to predict bleeding in patients on anticoagulant treatment. A systematic search was executed in three databases: Medline, Embase, and Cochrane. Seven studies were included; two were of good methodological quality. One study showed that patients on warfarin with INRs in range (2-3) admitted for hemorrhage ( = 28), had lower CAT-TG levels (endogenous thrombin potential [ETP]: 333 ± 89 nM/min) than patients on warfarin admitted for other reasons (ETP: 436 ± 207 nM/min; < 0.001). Another study found no difference in ETP or peak levels between bleeding and nonbleeding patients in PPP or PRP. When measured in whole blood, both levels were significantly lower in patients with bleeding compared with nonbleeding patients (median [interquartile range, IQR] ETP: 182.5 [157.2-2,847 nM/min] vs. median [IQR] ETP: 256.2 [194.9-344.2 nM/min]; < 0.001) and median [IQR] peak: 23.9 [19.6-41.8 nM] vs. median [IQR] peak: 39.1 [24.9-53.2 nM]; < 0.05). From the remaining studies, four suggested that CAT-TG is more sensitive in detecting hemostatic abnormalities than INR and one article found ETP and INR to be equally useful. However, insufficient data were provided to validate these conclusions. Studies investigating the direct association between decreased CAT-TG values and hemorrhagic events are rare. Therefore, the clinical consequences of low CAT-TG values remain to be further investigated.
出血是抗凝治疗期间令人担忧的不良事件。在服用维生素K拮抗剂的患者中，大多数出血事件发生在国际标准化比值（INR）处于治疗范围内时。目前，通过实验室方法识别高危患者并不可靠。在这项系统评价中，我们评估了校准自动凝血酶生成检测（CAT-TG）预测抗凝治疗患者出血的能力。
医学期刊数据库（Medline）、荷兰医学文摘数据库（Embase）和考克兰系统评价数据库（Cochrane）。
纳入了七项研究；两项研究的方法学质量良好。一项研究表明，因出血入院的华法林治疗患者（n = 28），国际标准化比值（INR）在2至3之间，其CAT-TG水平（内源性凝血酶潜能[ETP]：333±89 nM/min）低于因其他原因入院的华法林治疗患者（ETP：436±207 nM/min；P < 0.001）。另一项研究发现，在血浆或富血小板血浆中，出血患者与未出血患者的ETP或峰值水平无差异。当在全血中测量时，出血患者的这两个水平均显著低于未出血患者（中位数[四分位间距，IQR]ETP：182.5[157.2 - 2847 nM/min] vs. 中位数[IQR]ETP：256.2[194.9 - 344.2 nM/min]；P < 0.001），中位数[IQR]峰值：23.9[19.6 - 41.8 nM] vs. 中位数[IQR]峰值：39.1[24.9 - 53.2 nM]；P < 0.05）。在其余研究中，四项研究表明CAT-TG在检测止血异常方面比INR更敏感，一篇文章发现ETP和INR同样有用。然而，所提供的数据不足以验证这些结论。
研究CAT-TG值降低与出血事件之间直接关联的研究很少。因此，低CAT-TG值的临床后果仍有待进一步研究。
