Department of Preclinical Research and Development, CSL Behring GmbH, Marburg, Germany.
Br J Anaesth. 2010 Nov;105(5):576-82. doi: 10.1093/bja/aeq216. Epub 2010 Aug 17.
Extracorporeal circuit priming and intravascular volume expansion during cardiopulmonary bypass (CPB) may lead to dilutional coagulopathy and excessive diffuse postoperative bleeding. Prothrombin complex concentrate (PCC) containing clotting factors II (FII), VII (FVII), IX (FIX), and X (FX) could be of potential value in correcting dilutional coagulopathy and reducing blood loss.
Anaesthetized pigs underwent CPB with hypothermia for 2 h at 25°C followed by 1 h of normothermia. Approximately 1 h after CPB, animals randomly received either isotonic saline 1 ml kg⁻¹ or PCC 30 IU kg⁻¹ in a volume of 1 ml kg⁻¹. Diffuse coagulopathic bleeding was assessed as suture hole blood loss from a Gore-Tex patch placed over a full-thickness incision in the left carotid artery.
After CPB, levels of FII, FVII, FIX, and FX declined from baseline by 32% to 48%, and PCC fully or partially reversed those deficits. Median suture hole blood loss after administration of saline placebo was 74 ml. PCC reduced suture hole bleeding by a median of 54 ml with a 95% confidence interval of 6-112 ml (P=0.026) compared with saline. PCC, but not saline, normalized skin bleeding time. Peak thrombin generation markedly decreased after CPB, but then returned in PCC-treated animals to a level higher than baseline by 28.7 nM (14.5-41.1 nM; P=0.031).
PCC was effective in correcting dilutional coagulopathy and reducing diffuse bleeding in an in vivo large-animal CPB model. Further research is warranted on PCC as a haemostatic agent in CPB.
体外循环（CPB）过程中外周管道预充和血管内容量扩张可能导致稀释性凝血障碍和过度弥漫性术后出血。含有凝血因子 II（FII）、VII（FVII）、IX（FIX）和 X（FX）的凝血酶原复合物浓缩物（PCC）在纠正稀释性凝血障碍和减少失血方面可能具有潜在价值。
麻醉猪在 25°C 下进行 2 小时的低温 CPB，随后进行 1 小时的常温 CPB。CPB 后约 1 小时，动物随机接受等渗盐水 1ml/kg 或 PCC 30IU/kg，体积均为 1ml/kg。弥漫性凝血障碍性出血通过在左颈动脉全层切口上放置 Gore-Tex 补丁，评估缝合孔失血来评估。
CPB 后，FII、FVII、FIX 和 FX 水平从基线下降 32%至 48%，而 PCC 完全或部分逆转了这些缺陷。给予生理盐水安慰剂后，缝合孔出血量中位数为 74ml。与生理盐水相比，PCC 可使缝合孔出血中位数减少 54ml，95%置信区间为 6-112ml（P=0.026）。PCC 可使皮肤出血时间正常化，而生理盐水则不能。CPB 后最大凝血酶生成明显下降，但在 PCC 治疗动物中，凝血酶生成恢复到高于基线水平的 28.7nM（14.5-41.1nM；P=0.031）。
PCC 可有效纠正 CPB 中的稀释性凝血障碍和减少弥漫性出血。需要进一步研究 PCC 作为 CPB 中的止血剂。
