Hubbard W Brad, Sim Martha M S, Saatman Kathryn E, Sullivan Patrick G, Wood Jeremy P
Lexington Veterans' Affairs Healthcare System Lexington Kentucky USA.
Department of Physiology University of Kentucky Lexington Kentucky USA.
Res Pract Thromb Haemost. 2022 Jun 8;6(4):e12734. doi: 10.1002/rth2.12734. eCollection 2022 May.
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 nMmin endogenous thrombin potential) and 24 hours (131.0 ± 34.0 vs 32.1 ± 20.6 nMmin) 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.
创伤性脑损伤（TBI）会导致神经血管损伤，引发体内高凝机制，这可能会促使危及生命的并发症的发生，如凝血病和延迟性血栓形成。临床研究推测，组织因子（TF）在TBI后会诱导血液高凝状态；然而，尚无研究直接证实这种关系。
在本研究中，我们采用逐步深入的方法来了解实验性TBI后驱动凝血酶生成的因素。
我们采用制造挫伤的控制性皮质撞击（CCI）模型和弥漫性闭合性颅脑损伤（CHI）模型，研究这些机制与损伤严重程度和类型的关系。在损伤后6小时和24小时采集全血，并用乏血小板血浆来测量凝血酶生成和细胞外囊泡（EV）TF。
我们发现，依赖于血浆中存在的TF的血浆凝血酶生成，在CCI损伤的动物中，在损伤后6小时（内源性凝血酶潜力为120.4±36.9 vs 0.0±0.0 nMmin）和24小时（131.0±34.0 vs 32.1±20.6 nMmin）均高于假手术组。CCI损伤后24小时（328.6±62.1 vs 167.7±20.8 fM），EV TF显著增加。此外，CHI损伤后6小时（126.6±17.1 vs 63.3±14.4 fM）EV TF也增加，但24小时时未增加。
损伤后TF介导的凝血酶生成具有时间依赖性，与CCI相比，CHI后TF增加的消退更早。综上所述，这些数据支持TBI后TF介导的凝血酶生成途径，并指出TF是TBI诱导的凝血病的主要因素。
