Moe Donald Michael, Lallemand Michael Scott, McClellan John Mason, Smith Joshua Porter, Marko Shannon T, Eckert Matthew J, Martin Matthew J
From the Madigan Army Medical Center (D.M.M., M.S.L., J.M.M., J.P.S., S.T.M., M.J.E, M.J.M.), Tacoma, Washington; and Trauma and Emergency Surgery Service, Legacy Emanuel Medical Center (M.J.M.), Portland, Oregon.
J Trauma Acute Care Surg. 2017 Dec;83(6):1114-1123. doi: 10.1097/TA.0000000000001646.
Bleeding is a leading cause of preventable death after severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor PCC (3PCC) versus 4-factor PCC (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy.
Twenty-five adult Yorkshire swine underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized crystalloid resuscitation. Seventeen animals were randomized at 4 hours after model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional eight animals received autologous plasma transfusion before 4PCC to better characterize response to PCC. Individual factor levels were drawn at 4 hours and 6 hours.
The model created significant acidosis with mean pH of 7.21 and lactate of 9.6 mmol/L. After PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed consumptive coagulopathy. The animals that developed consumptive coagulopathy had manifested the "lethal triad" with lower temperatures (36.3°C vs. 37.8°C), increased acidosis (pH, 7.14 vs. 7.27; base excess, -12.1 vs. -6.5 mEq/L), and worse coagulopathy (prothrombin time, 17.1 vs. 14.6 seconds; fibrinogen, 87.9 vs. 124.1 mg/dL) (all p < 0.05). In the absence of a consumptive coagulopathy, 3PCC and 4PCC improved individual clotting factors with transient improvement of prothrombin time, but there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy.
PCC failed to correct coagulopathy and was associated with fibrinogen and platelet depletion. Of greater concern, PCC administration resulted in consumptive coagulopathy in the more severely ill animals. The incidence of consumptive coagulopathy was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting.
出血是严重创伤后可预防死亡的主要原因。凝血酶原复合物浓缩剂（PCC）用于治疗先天性凝血障碍和逆转口服抗凝剂，但被提议用于“基于因子”的复苏策略。针对酸中毒情况下该适应症的研究较少，也鲜有比较三因子PCC（3PCC）与四因子PCC（4PCC）产品的研究。我们旨在评估和比较它们在严重失血性休克和凝血病猪模型中的安全性和有效性。
25只成年约克夏猪经历35%血容量出血、缺血再灌注损伤以及标准化晶体液复苏。17只动物在模型建立后4小时随机分组，接受45 IU/kg剂量的3PCC或4PCC。另外8只动物在接受4PCC之前输注自体血浆，以更好地描述对PCC的反应。在4小时和6小时采集个体因子水平。
该模型产生了显著酸中毒，平均pH值为7.21，乳酸水平为9.6 mmol/L。给予PCC后，3PCC组66.7%的动物和4PCC组25%的动物（无论是否输注血浆）发生消耗性凝血病。发生消耗性凝血病的动物出现了“致死三联征”，体温较低（36.3°C对37.8°C）、酸中毒加重（pH值，7.14对7.27；碱剩余，-12.1对-6.5 mEq/L）以及凝血病更严重（凝血酶原时间，17.1对14.6秒；纤维蛋白原，87.9对124.1 mg/dL）（所有p<0.05）。在未发生消耗性凝血病的情况下，3PCC和4PCC可改善个体凝血因子，凝血酶原时间有短暂改善，但纤维蛋白原和血小板显著消耗，凝血病无持久改善。
PCC未能纠正凝血病，且与纤维蛋白原和血小板消耗有关。更令人担忧的是，给予PCC导致病情较重的动物发生消耗性凝血病。与4PCC相比，3PCC导致消耗性凝血病的发生率显著增加，在此情况下应谨慎使用这些产品。
