BACKGROUND Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity. METHODS Citrated whole blood obtained from 13 healthy volunteers underwent a 50% crystalloid dilution (DL-50%), followed by spiking with four-factor prothrombin complex concentrate (DL-50% + 4F-PCC). Changes in thrombin generation activity were compared with the VET parameters CT and ACT derived from four commercially available viscoelastic devices (ROTEM® Delta, ClotPro®, TEG®6s, and Quantra®) and standard coagulation tests. RESULTS Dilution of whole blood resulted in a marked increase in velocity index, peak height, and endogenous thrombin potential (all P<0.01), with a further substantial increase after spiking with 4F-PCC (all P<0.001). In contrast, CT and ACT were significantly prolonged in response to DL-50% on all devices (all P<0.05). Subsequent spiking of diluted blood with 4F-PCC had no impact on CT and ACT derived from VET analysers, but it restored standard coagulation tests without reaching baseline values (all P<0.01). CONCLUSIONS Upregulated thrombin generation parameters after PCC spiking were not displayed by CT, ACT, or standard tests. Our results do not support treatment algorithms using prolonged CT or ACT as a trigger for administration of PCC to augment thrombin generation.

中文翻译：

---

粘弹性测试未检测到凝血酶原复合物浓缩物的凝血酶生成改变：一项体外研究。


背景 出血指南目前推荐在严重出血中使用粘弹性测试 （VET） 来指导止血复苏。然而，凝血酶生成测定所揭示的凝血起始的 VET 衍生参数，例如凝血时间 （CT） 和活化凝血时间 （ACT），可能无法充分反映促凝血和抗凝血活性的临床相关相互作用。本研究的目的是评估 CT 和 ACT 指示凝血酶生成活性的能力。方法 从 13 名健康志愿者获得的柠檬酸盐全血进行 50% 晶体稀释 （DL-50%），然后用四因子凝血酶原复合物浓缩物 （DL-50% + 4F-PCC） 加标。将凝血酶生成活性的变化与来自四种市售粘弹性装置 （ROTEM® Delta、ClotPro®、TEG®6s 和 Quantra®） 和标准凝血试验的 VET 参数 CT 和 ACT 进行比较。结果 稀释全血导致速度指数、峰高和内源性凝血酶电位显著增加（均 P<0.01），加标 4F-PCC 后进一步显著增加（均 P<0.001）。相比之下，在所有设备上，CT 和 ACT 响应 DL-50% 显著延长 （均 P<0.05）。随后用 4F-PCC 加标稀释血液对 VET 分析仪得出的 CT 和 ACT 没有影响，但它恢复了标准凝血试验，未达到基线值 （均 P<0.01）。结论 CT、ACT 或标准测试未显示 PCC 加标后凝血酶生成参数上调。我们的结果不支持使用延长 CT 或 ACT 作为 PCC 给药以增强凝血酶生成的触发因素的治疗算法。