Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Br J Anaesth. 2018 Oct;121(4):936-943. doi: 10.1016/j.bja.2018.05.063. Epub 2018 Jul 4.
Prothrombin complex concentrate (PCC) is increasingly used to correct acquired coagulopathy in trauma and surgery. Dosing of PCC is guided by the prothrombin time, which only reflects the onset of thrombin generation, but does not account for variations in intrinsic pathway coagulation factors, including factor IX (FIX). We hypothesised that FIX contained in PCC could strongly influence thrombin generation patterns.
Pooled normal, FIX-deficient, and warfarinised plasma were used to analyse the effects of FIX contained in PCC. PCC was evaluated at final concentrations of 0.2 and 0.4 IU ml in FIX-deficient and normal plasma, and at 0.6 IU ml in warfarinised plasma with elevated FVIII (1.5 IU ml), 40% dilution with saline, or both. The effects on thrombin generation were assessed by measuring both procoagulant and inhibitory segments.
FIX-deficient plasma had lower peak thrombin generation [30.6 (20.5-35.8) nM vs 130.2 (107-168) nM] and endogenous thrombin potential [472 (391-532) nM vs 1096 (958-1190) nM] than normal plasma. PCC addition resulted in significant increases of peak thrombin generation [81.8 (37.3-98.3) nM] and endogenous thrombin potential [808 (472-842) nM] in FIX-deficient plasma. The combination of FVIII and PCC resulted in greater increases relative to each agent alone, restoring normal thrombin generation. After 40% dilution, adding PCC, FVIII, or both, to FIX-deficient plasma increased peak thrombin generation, and prolonged the inhibitory phase of the endogenous thrombin potential.
FIX derived from PCC strongly enhances tissue factor-triggered thrombin generation in the presence of elevated FVIII activity. Haemodilution further enhances procoagulant effects of FIX and FVIII by slowing down inhibition of procoagulant enzymes. Dosing of PCC per prothrombin time may underestimate PCC's procoagulant potential because it does not account for intrinsic tenase or antithrombin activity.
凝血酶原复合物浓缩物（PCC）越来越多地被用于纠正创伤和手术中的获得性凝血障碍。PCC 的剂量由凝血酶原时间指导，该时间仅反映凝血酶生成的开始，但不考虑包括因子 IX（FIX）在内的内在途径凝血因子的变化。我们假设 PCC 中包含的 FIX 会强烈影响凝血酶生成模式。
使用混合的正常、FIX 缺乏和华法林化血浆来分析 PCC 中包含的 FIX 的影响。在 FIX 缺乏和正常血浆中，PCC 终浓度分别为 0.2 和 0.4 IU/ml，在华法林化血浆中，FVIII 升高（1.5 IU/ml）、生理盐水 40%稀释或两者同时进行评估。通过测量促凝和抑制片段来评估对凝血酶生成的影响。
FIX 缺乏的血浆的峰值凝血酶生成[30.6（20.5-35.8）nM 比 130.2（107-168）nM]和内源性凝血酶潜能[472（391-532）nM 比 1096（958-1190）nM]低于正常血浆。PCC 的加入导致 FIX 缺乏的血浆中峰值凝血酶生成[81.8（37.3-98.3）nM]和内源性凝血酶潜能[808（472-842）nM]显著增加。FVIII 和 PCC 的联合作用相对于单独使用每种药物产生更大的增加，恢复了正常的凝血酶生成。在 40%稀释后，向 FIX 缺乏的血浆中添加 PCC、FVIII 或两者均增加了峰值凝血酶生成，并延长了内源性凝血酶潜能的抑制阶段。
在 FVIII 活性升高的情况下，来自 PCC 的 FIX 强烈增强组织因子触发的凝血酶生成。血液稀释通过减缓对促凝酶的抑制作用进一步增强 FIX 和 FVIII 的促凝作用。根据凝血酶原时间给 PCC 给药可能会低估 PCC 的促凝潜力，因为它没有考虑内在的凝血酶原酶或抗凝血酶活性。
