Martini Wenjun Z, Cortez Douglas S, Dubick Michael A, Park Myung S, Holcomb John B
The US Army Institute of Surgical Research, 3400 Rawley E. Chambers Avenue, Ft. Sam Houston, TX 78234, USA.
J Trauma. 2008 Sep;65(3):535-43. doi: 10.1097/TA.0b013e31818379a6.
Hypothermia and hemorrhagic shock contribute to coagulopathy after trauma. In this study, we investigated the independent and combined effects of hypothermia and hemorrhage with resuscitation on coagulation in swine and evaluated clinically relevant tests of coagulation.
Pigs (n = 24) were randomized into four groups of six animals each: sham control, hypothermia, hemorrhage with resuscitation, and hypothermia, hemorrhage with resuscitation combined. Hypothermia to 32 degrees C was induced with a cold blanket. Hemorrhage was induced by bleeding 35% of total blood volume followed by resuscitation with lactated Ringer's solution. Coagulation was assessed by thrombin generation, prothrombin time (PT), activated partial thromboplastin time (aPTT), activated clotting time (ACT), and thrombelastography (TEG) from blood samples taken at baseline and 4 hour after hypothermia and/or hemorrhage with resuscitation. Data were compared with analysis of variance.
Baseline values were similar among groups. There were no changes in any measurements in the control group. Compared with baseline values, hemorrhage with resuscitation increased lactate to 140% +/- 15% (p < 0.05). Hypothermia decreased platelets to 73% +/- 3% (p < 0.05) with no effect on fibrinogen. Hemorrhage with resuscitation reduced platelets to 72% +/- 4% and fibrinogen to 71% +/- 3% (both p < 0.05), with similar decreases in platelets and fibrinogen observed in the combined group. Thrombin generation was decreased to 75% +/- 4% in hypothermia, 67% +/- 6% in hemorrhage with resuscitation, and 75% +/- 10% in the combined group (all p < 0.05). There were no significant changes in PT or aPTT by hemorrhage or hypothermia. ACT was prolonged to 122% +/- 1% in hypothermia, 111% +/- 4% in hemorrhage with resuscitation, and 127% +/- 3% in the combined group (all p < 0.05). Hypothermia prolonged the initial clotting time (R) and clot formation time (K), and decreased clotting rapidity (alpha) (all p < 0.05). Hemorrhage with resuscitation only decreased clot strength (maximum amplitude [MA], p < 0.05). TEG parameters in the combined group reflected the abnormal R, K, MA, and alpha observed in the other groups.
Hypothermia inhibited clotting times and clotting rate, whereas hemorrhage impaired clot strength. Combining hypothermia with hemorrhage impaired all these clotting parameters. PT, aPTT were not sensitive whereas ACT was not specific in detecting these coagulation defects. Only TEG differentiated mechanism related to clotting abnormalities, and thus may allow focused treatment of clotting alterations associated with hypothermia and hemorrhagic shock.
体温过低和失血性休克会导致创伤后凝血病。在本研究中，我们调查了体温过低和出血复苏对猪凝血的独立及联合影响，并评估了临床相关的凝血检测。
将猪（n = 24）随机分为四组，每组六只动物：假手术对照组、体温过低组、出血复苏组以及体温过低与出血复苏联合组。使用冷毯将体温降至32摄氏度。通过抽取总血容量的35%进行放血，随后用乳酸林格氏液进行复苏来诱导出血。在基线以及体温过低和/或出血复苏后4小时采集血样，通过凝血酶生成、凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）、活化凝血时间（ACT）和血栓弹力图（TEG）评估凝血情况。数据采用方差分析进行比较。
各组基线值相似。对照组的各项测量指标均无变化。与基线值相比，出血复苏使乳酸水平升至140%±15%（p < 0.05）。体温过低使血小板降至73%±3%（p < 0.05），对纤维蛋白原无影响。出血复苏使血小板降至72%±4%，纤维蛋白原降至71%±3%（均p < 0.05），联合组的血小板和纤维蛋白原也出现类似程度的下降。凝血酶生成在体温过低组降至75%±4%，出血复苏组降至67%±6%，联合组降至75%±10%（均p < 0.05）。出血或体温过低对PT或aPTT无显著影响。ACT在体温过低组延长至122%±1%，出血复苏组延长至111%±4%，联合组延长至127%±3%（均p < 0.05）。体温过低延长了初始凝血时间（R）和凝块形成时间（K），并降低了凝血速度（α）（均p < 0.05）。出血复苏仅降低了凝块强度（最大振幅[MA]，p < 0.05）。联合组的TEG参数反映了其他组中观察到的R、K、MA和α的异常情况。
体温过低抑制凝血时间和凝血速率，而出血损害凝块强度。体温过低与出血联合损害了所有这些凝血参数。PT、aPTT在检测这些凝血缺陷时不敏感，而ACT不具有特异性。只有TEG能够区分与凝血异常相关的机制，因此可能有助于针对性治疗与体温过低和失血性休克相关的凝血改变。
