larly, the ideal diagnostic trigger for their administration and potential differences between heparin-containing and heparin-free preparations remain unclear. We investigated the hypothesis that 2 different PCCs might have distinct influences on in vitro blood coagulation. METHODS: We conducted a direct comparison of 2 commercially available PCC preparations (the heparin-containing Beriplex P/N and the heparin-free Cofact) in an in vitro hemodilution model. Sole fibrinogen substitution served as the control group. To characterize the hemostatic changes, we utilized conventional coagulation tests, a thrombin generation assay (TGA), and 2 different viscoelastic hemostatic assays (VHAs; ROTEM delta and ClotPro). RESULTS: Irrespective of the diagnostic assay used, no significant differences between the 2 PCC groups were observed. Fibrinogen levels remained stable from the baseline throughout every dilution level. The control group already showed an increased endogenous thrombin potential (ETP; nM·L−1·min−1) at all dilution levels compared to baseline (baseline, 2829.4 (432.8); 40% dilution, 4211.7 (391.6); 60% dilution, 4290.9 (300.8); 80% dilution, 3861.4 (303.5); all P < .001). Spiking with both PCC preparations led to a further-pronounced thrombin elevation in comparison to the control group (ETP at 40% dilution, PCC1: 4913.3 [370.2], PCC2: 4988.1 [265.7]; 60% dilution, PCC1: 5174.5 [234.7], PCC2: 5390.4 [334.9]; 80% dilution, PCC1: 5253.8 [357.9], PCC2: 5392.6 [313.4]; all P < .001). Conventional coagulation tests did not mirror the TGA results. Despite increased thrombin generation, prothrombin time was significantly prolonged at all dilution levels for the control group, and both PCC groups exhibited significant prolongations at the 60% and 80% dilution levels (all P < .001) compared to baseline. Similarly, VHA did not depict the thrombin elevation. Furthermore, descriptive analyses revealed relevant differences between the 2 VHA devices, particularly at baseline. CONCLUSIONS: Both PCC preparations (ie, irrespective of heparin content) induced significant elevation of thrombin generation, which was not depicted by conventional coagulation tests or VHA. Our in vitro results suggest that diagnostic assays routinely used to guide PCC administration might not adequately reflect thrombin generation in bleeding patients....

中文翻译：

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在体外血液稀释模型中通过不同的止血测定法表征 2 种不同的凝血酶原复合浓缩物

最近，它们给药的理想诊断触发因素以及含肝素和无肝素制剂之间的潜在差异仍不清楚。我们研究了 2 种不同的 PCC 可能对体外凝血有不同影响的假设。方法：我们在体外血液稀释模型中对 2 种市售 PCC 制剂（含肝素的 Beriplex P/N 和不含肝素的 Cofact）进行了直接比较。单独的纤维蛋白原替代作为对照组。为了表征止血变化，我们使用了常规凝血试验、凝血酶生成试验 (TGA) 和 2 种不同的粘弹性止血试验（VHA；ROTEM delta 和 ClotPro）。结果：无论使用何种诊断方法，在 2 个 PCC 组之间均未观察到显着差异。在每个稀释水平中，纤维蛋白原水平从基线开始保持稳定。与基线（基线，2829.4 (432.8)；40% 稀释，4211.7 (391.6)；60% 稀释）相比，对照组在所有稀释水平下已经显示内源性凝血酶潜能（ETP；nM·L−1·min−1）增加, 4290.9 (300.8)；80% 稀释，3861.4 (303.5)；所有 P < .001)。与对照组相比，加入两种 PCC 制剂导致凝血酶升高更明显（ETP，40% 稀释，PCC1：4913.3 [370.2]，PCC2：4988.1 [265.7]；60% 稀释，PCC1：5174.5 [234.7] ，PCC2：5390.4 [334.9]；80% 稀释，PCC1：5253.8 [357.9]，PCC2：5392.6 [313.4]；所有 P < .001)。传统的凝血试验不能反映 TGA 结果。尽管凝血酶生成增加，与基线相比，对照组在所有稀释水平下的凝血酶原时间均显着延长，并且两个 PCC 组在 60% 和 80% 稀释水平下均表现出显着延长（所有 P <.001）。同样，VHA 没有描述凝血酶升高。此外，描述性分析揭示了 2 种 VHA 设备之间的相关差异，尤其是在基线时。结论：两种 PCC 制剂（即，不考虑肝素含量）均导致凝血酶生成显着升高，而传统凝血试验或 VHA 并未描述这一点。我们的体外结果表明，常规用于指导 PCC 给药的诊断测定可能无法充分反映出血患者的凝血酶生成…… 与基线相比，两个 PCC 组在 60% 和 80% 稀释水平（所有 P < .001）均表现出显着延长。同样，VHA 没有描述凝血酶升高。此外，描述性分析揭示了 2 种 VHA 设备之间的相关差异，尤其是在基线时。结论：两种 PCC 制剂（即，不考虑肝素含量）均导致凝血酶生成显着升高，而传统凝血试验或 VHA 并未描述这一点。我们的体外结果表明，常规用于指导 PCC 给药的诊断测定可能无法充分反映出血患者的凝血酶生成…… 与基线相比，两个 PCC 组在 60% 和 80% 稀释水平（所有 P < .001）均表现出显着延长。同样，VHA 没有描述凝血酶升高。此外，描述性分析揭示了 2 种 VHA 设备之间的相关差异，尤其是在基线时。结论：两种 PCC 制剂（即，不考虑肝素含量）均导致凝血酶生成显着升高，而传统凝血试验或 VHA 并未描述这一点。我们的体外结果表明，常规用于指导 PCC 给药的诊断测定可能无法充分反映出血患者的凝血酶生成…… 特别是在基线。结论：两种 PCC 制剂（即，不考虑肝素含量）均导致凝血酶生成显着升高，而传统凝血试验或 VHA 并未描述这一点。我们的体外结果表明，常规用于指导 PCC 给药的诊断测定可能无法充分反映出血患者的凝血酶生成…… 特别是在基线。结论：两种 PCC 制剂（即，不考虑肝素含量）均导致凝血酶生成显着升高，而传统凝血试验或 VHA 并未描述这一点。我们的体外结果表明，常规用于指导 PCC 给药的诊断测定可能无法充分反映出血患者的凝血酶生成……