Thrombin generation in trauma patients

Thrombin generation in trauma patients
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DOI:
10.1111/j.1537-2995.2009.02335.x
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发表时间:
2009-12-01
期刊:
影响因子:
2.9
通讯作者:
Chandler, Wayne L.
Chandler, Wayne L.
中科院分区:
医学3区
文献类型:
--
作者:
Dunbar, Nancy M.;Chandler, Wayne L.

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背景:创伤患者有发生与组织损伤、休克和血液稀释相关的创伤急性凝血病(ACT)的风险。ACT是不完全了解,但类似于弥散性血管内凝血(DIC),并与不良outcome.Study设计和方法:凝血酶生成测定被用来评估血浆止血在42创伤患者,25正常受试者,45例华法林和在实验室制备的因子减少血浆。在15名创伤患者中,凝血酶原时间(PT)延长,超过18秒,或国际标准化比值大于1.5,表明可能的ACT。天然凝血酶生成(未添加激活剂,接触激活阻断)显示,与正常患者相比,ACT创伤患者的滞后时间缩短68%,峰值凝血酶生成高出3倍,表明存在能够全身启动凝血的循环促凝剂。创伤患者的血小板计数、纤维蛋白原和因子(F)II水平较低,使其出血风险增加。在实验室制备的单独的因子减少的样本中,以及华法林导致的维生素K依赖因子缺乏症患者中,凝血酶生成与FIB水平成正比。相反,在稀释的血浆和因子水平降低的创伤患者中,凝血酶生成增加,并与凝血酶生成的较慢抑制有关(终止时间延长)和抗凝血酶水平降低(43%的创伤与ACT正常)。凝血酶生成研究表明,ACT患者的创伤显示止血失调,其特征为过度的非伤口-由于能够全身性激活凝血的循环促凝剂和降低的抑制剂水平的组合,从而允许全身性凝血酶生成一旦开始就继续,导致相关的凝血酶生成。
BACKGROUND: Trauma patients are at risk of developing an acute coagulopathy of trauma ( ACT) related to tissue injury, shock, and hemodilution. ACT is incompletely understood, but is similar to disseminated intravascular coagulation (DIC) and is associated with poor outcome.STUDY DESIGN AND METHODS: Thrombin generation assays were used to evaluate plasma hemostasis in 42 trauma patients, 25 normal subjects, and 45 patients on warfarin and in laboratory-prepared factor reduced plasma.RESULTS: Prolonged prothrombin time ( PT), more than 18 seconds, or an international normalized ratio of greater than 1.5 was present in 15 trauma patients indicating possible ACT. Native thrombin generation (no activator added, contact activation blocked) showed that Trauma with ACT patients had lag times 68% shorter and peak thrombin generation threefold higher than normal patients indicating the presence of circulating procoagulants capable of initiating coagulation systemically. Trauma patients had lower platelet counts and fibrinogen and Factor (F)II levels putting them at increased risk of bleeding. In laboratory-prepared isolated factor-reduced samples and in patients with vitamin K-dependent factor deficiency due to warfarin, thrombin generation decreased in direct proportion to FII levels. In contrast, in diluted plasma and in trauma patients with reduced factor levels, thrombin generation was increased and associated with slower inhibition of thrombin generation ( prolonged termination time) and decreased antithrombin levels (43% of normal in Trauma with ACT).CONCLUSIONS: Thrombin generation studies indicate that Trauma with ACT patients show dysregulated hemostasis characterized by excessive non-wound-related thrombin generation due to a combination of circulating procoagulants capable of activating coagulation systemically and reduced inhibitor levels allowing systemic thrombin generation to continue once started.