氨甲环酸和凝血酶原复合物浓缩物对创伤性凝血病的影响：体外分析严重酸中毒的影响。
The effects of tranexamic acid and prothrombin complex concentrate on the coagulopathy of trauma: an in vitro analysis of the impact of severe acidosis.
机构信息
From the Departments of Surgery (C.P., D.N., D.M., M.E., M.M.), and Clinical Investigations (S.S.), Madigan Army Medical Center, Tacoma, Washington; and Department of Surgery (S.I., M.M.), Legacy Emanuel Medical Center, Portland, Oregon.
出版信息
J Trauma Acute Care Surg. 2013 Dec;75(6):954-60. doi: 10.1097/TA.0b013e31829e20bf.
BACKGROUND
Bleeding is the most frequent cause of preventable death after severe injury. Our purposes were to study the efficacy of tranexamic acid (TXA) and prothrombin complex concentrate (PCC) on a traumatic coagulopathy with a severe native metabolic acidosis and compare the efficacy of PCC versus fresh frozen plasma (FFP) to reverse a dilutional coagulopathy.
METHODS
In vitro effects of TXA and PCC were assessed with standard laboratory analysis (prothrombin time [PT]/international normalized ratio [INR]) and rotational thromboelastometry in a porcine hemorrhage with ischemia-reperfusion (H/I) model. FFP was used in comparison with PCC. In vitro doses were calculated to be the equivalent of 1-g TXA, 100-mg tissue plasminogen activator, 45-IU/kg PCC, and 4-U FFP. Agents were tested at baseline and then with severe metabolic acidosis after 6 hours of resuscitation.
RESULTS
Thirty-one swine were studied. Baseline hematocrit was 24%, pH was 7.56, INR was 1.0, and lactate level was 1.47. Six hours after H/I, the hematocrit was 15.9%, pH was 7.1, INR was 1.7, and lactate level was 10.26. Rotational thromboelastometry revealed that maximum clot firmness at baseline was 71.71 mm and decreased to 0.29 mm with tissue plasminogen activator, representing severe fibrinolysis. Following TXA dosing, the maximum clot firmness was immediately corrected to 69.06 mm. There was no difference (p = 0.48) between TXA function at baseline pH (mean, 7.56) or acidotic pH (mean, 7.11). The mean baseline PT was 13 ± 0.49 seconds (INR, 1). After H/I and resuscitation, the mean PT was 23.03 seconds (INR, 2.1). PCC reduced the PT to 20 (INR, 1.75; p = 0.001) and FFP to 17.44 (INR, 1.47; p = 0.001).
CONCLUSION
Both TXA and PCC seem to function well in reversing a traumatic coagulopathy in vitro, and TXA seems to have no loss of function in a severe metabolic acidosis. Further investigations are warranted.
背景
出血是严重创伤后可预防死亡的最常见原因。我们的目的是研究氨甲环酸（TXA）和凝血酶原复合物浓缩物（PCC）在创伤性凝血病伴严重原发性代谢性酸中毒中的疗效，并比较 PCC 与新鲜冷冻血浆（FFP）逆转稀释性凝血病的疗效。
方法
在猪出血伴缺血再灌注（H/I）模型中，采用标准实验室分析（凝血酶原时间[PT]/国际标准化比值[INR]）和旋转血栓弹性测定法评估 TXA 和 PCC 的体外作用。FFP 与 PCC 进行比较。体外剂量计算为 1g TXA、100mg 组织型纤溶酶原激活剂、45IU/kg PCC 和 4U FFP 相当。在基线和复温 6 小时后出现严重代谢性酸中毒时检测药物。
结果
研究了 31 头猪。基线时红细胞压积为 24%，pH 值为 7.56，INR 为 1.0，乳酸水平为 1.47。H/I 后 6 小时，红细胞压积为 15.9%，pH 值为 7.1，INR 为 1.7，乳酸水平为 10.26。旋转血栓弹性测定显示，基线时最大凝块硬度为 71.71mm，用组织型纤溶酶原激活剂降至 0.29mm，代表严重的纤溶。TXA 给药后，最大凝块硬度立即纠正至 69.06mm。TXA 在基础 pH 值（平均 7.56）或酸中毒 pH 值（平均 7.11）下的功能无差异（p=0.48）。基础 PT 平均为 13±0.49 秒（INR 为 1）。H/I 及复温后，PT 平均为 23.03 秒（INR 为 2.1）。PCC 将 PT 降至 20（INR 为 1.75；p=0.001），FFP 降至 17.44（INR 为 1.47；p=0.001）。
结论
TXA 和 PCC 似乎都能很好地逆转体外创伤性凝血病，TXA 在严重代谢性酸中毒时似乎没有功能丧失。需要进一步研究。
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