Tissue factor release following traumatic brain injury drives thrombin generation.
Tissue factor release following traumatic brain injury drives thrombin generation.
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创伤性脑损伤后组织因子释放驱动凝血酶生成。
DOI：
10.1002/rth2.12734
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发表时间：
2022-05
影响因子：
4.6
通讯作者：
Wood, Jeremy P.
中科院分区：
文献类型：
--
作者：
Hubbard, W. Brad;Sim, Martha M. S.;Saatman, Kathryn E.;Sullivan, Patrick G.;Wood, Jeremy P.
关键词：
创伤性脑损伤（TBI）会导致神经血管损伤，从而引发高凝的内在机制，这可能导致危及生命的并发症的发生，例如凝血障碍和迟发性血栓形成。临床研究假设组织因子 (TF) 会在 TBI 后诱发高凝状态；然而，没有人直接表明这种关系。在当前的研究中，我们采取了逐步的方法来了解实验性 TBI 后驱动凝血酶生成的因素。我们采用产生挫伤的受控皮质撞击（CCI）模型和弥漫性闭合性头部损伤（CHI）模型来研究这些机制与损伤严重程度和方式的关系。损伤后 6 小时和 24 小时收集全血，并使用贫血小板血浆测量凝血酶生成和细胞外囊泡 (EV) TF。我们发现，与假手术相比，CCI 损伤的动物在 6 小时（120.4 ± 36.9 与 0.0 ± 0.0 nM*min 内源凝血酶电位）和 24 小时（131.0 ± 34.0 与32.1 ± 20.6 nM*min) 受伤后。与此同时，CCI 后 24 小时 EV TF 显着增加（328.6 ± 62.1 vs 167.7 ± 20.8 fM）。此外，EV TF 也会在 CHI 后 6 小时增加（126.6 ± 17.1 vs 63.3 ± 14.4 fM），但不会在 CHI 后 24 小时增加。 TF 介导的凝血酶生成在损伤后具有时间依赖性，与 CCI 相比，CHI 后 TF 的增加更早消退。总而言之，这些数据支持 TBI 后 TF 介导的凝血酶生成途径，并明确指出 TF 在 TBI 诱发的凝血病中发挥着主要作用。
Traumatic brain injury (TBI) results in neurovascular damage that initiates intrinsic mechanisms of hypercoagulation, which can contribute to the development of life‐threatening complications, such as coagulopathy and delayed thrombosis. Clinical studies have hypothesized that tissue factor (TF) induces hypercoagulability after TBI; however, none have directly shown this relationship. In the current study, we took a stepwise approach to understand what factors are driving thrombin generation following experimental TBI. We employed the contusion‐producing controlled cortical impact (CCI) model and the diffuse closed head injury (CHI) model to investigate these mechanisms as a function of injury severity and modality. Whole blood was collected at 6 hours and 24 hours after injury, and platelet‐poor plasma was used to measure thrombin generation and extracellular vesicle (EV) TF. We found that plasma thrombin generation, dependent on TF present in the plasma, was greater in CCI‐injured animals compared to sham at both 6 hours (120.4 ± 36.9 vs 0.0 ± 0.0 nM*min endogenous thrombin potential) and 24 hours (131.0 ± 34.0 vs 32.1 ± 20.6 nM*min) after injury. This was accompanied by a significant increase in EV TF at 24 hours (328.6 ± 62.1 vs 167.7 ± 20.8 fM) after CCI. Further, EV TF is also increased at 6 hours (126.6 ± 17.1 vs 63.3 ± 14.4 fM) but not 24 hours following CHI. TF‐mediated thrombin generation is time‐dependent after injury and TF increases resolve earlier following CHI as compared to CCI. Taken together, these data support a TF‐mediated pathway of thrombin generation after TBI and pinpoint TF as a major player in TBI‐induced coagulopathy.
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影响因子：
4.6
作者：
Hubbard, W. Brad;Harwood, Christopher L.;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
DOI：
10.1016/j.jss.2015.02.064
发表时间：
2015-07
期刊：
The Journal of surgical research
影响因子：
--
作者：
Midura EF;Jernigan PL;Kuethe JW;Friend LA;Veile R;Makley AT;Caldwell CC;Goodman MD
通讯作者：
Goodman MD
DOI：
10.1097/ta.0b013e31816493ad
发表时间：
2008-03-01
影响因子：
--
作者：
Morel, Nicolas;Morel, Olivier;Dabadie, Philippe
通讯作者：
Dabadie, Philippe
影响因子：
4.2
作者：
Nekludov, Michael;Mobarrez, Fariborz;Wallen, Hakan
通讯作者：
Wallen, Hakan
影响因子：
2.9
作者：
Maegele, Marc
通讯作者：
Maegele, Marc