Department of Surgery, University of California, San Francisco.
Department of Epidemiology and Biostatistics, University of California, San Francisco.
Shock. 2021 Feb 1;55(2):189-197. doi: 10.1097/SHK.0000000000001622.
Altered postinjury platelet behavior is recognized in the pathophysiology of trauma-induced coagulopathy (TIC), but the mechanisms remain largely undefined. Studies suggest that soluble factors released by injury may inhibit signaling pathways and induce structural changes in circulating platelets. Given this, we sought to examine the impact of treating healthy platelets with plasma from injured patients. We hypothesized that healthy platelets treated ex-vivo with plasma from injured patients with shock would impair platelet aggregation, while treatment with plasma from injured patients with significant injury burden, but without shock, would enhance platelet aggregation.
Plasma samples were isolated from injured patients (pretransfusion) and healthy donors at a Level I trauma center and stored at -80°C. Plasma samples from four separate patients in each of the following stratified clinical groups were used: mild injury/no shock (injury severity score [ISS] 2-15, base excess [BE]>-6), mild injury/with shock (ISS 2-15, BE≤-6), severe injury/no shock (ISS>25, BE>-6), severe injury/with shock (ISS>25, BE≤-6), minimal injury (ISS 0/1, BE>-6), and healthy. Platelets were isolated from three healthy adult males and were treated with plasma for 30 min. Aggregation was stimulated with a thrombin receptor agonist and measured via multiple-electrode platelet aggregometry. Data were normalized to HEPES Tyrode's (HT) buffer-only treated platelets. Associations of plasma treatment groups with platelet aggregation measures were tested with Mann-Whitney U tests.
Platelets treated with plasma from patients with shock (regardless of degree of injury) had significantly impaired thrombin-stimulated aggregation compared with platelets treated with plasma from patients without shock (P = 0.002). Conversely, platelets treated with plasma from patients with severe injury, but without shock, had amplified thrombin-stimulated aggregation (P = 0.030).
Shock-mediated soluble factors impair platelet aggregation, and tissue injury-mediated soluble factors amplify platelet aggregation. Future characterization of these soluble factors will support development of novel treatments of TIC.
创伤后血小板行为的改变在创伤性凝血病（TIC）的病理生理学中已得到公认，但其中的机制仍未完全明确。有研究表明，损伤释放的可溶性因子可能会抑制信号通路，并导致循环血小板的结构发生变化。鉴于此，我们试图研究用损伤患者的血浆处理健康血小板的影响。我们假设，用休克患者的血浆体外处理健康血小板，会损害血小板聚集，而用创伤但无休克且创伤严重程度高的患者的血浆处理健康血小板，则会增强血小板聚集。
在一级创伤中心从受伤患者（输血前）和健康供体中分离血浆样本，并储存在-80°C。在以下分层临床组的每个组中使用来自四个单独患者的血浆样本：轻度损伤/无休克（损伤严重程度评分[ISS]为 2-15，碱缺失[BE]＞-6）、轻度损伤/休克（ISS 为 2-15，BE≤-6）、严重损伤/无休克（ISS＞25，BE＞-6）、严重损伤/休克（ISS＞25，BE≤-6）、轻度损伤（ISS 0/1，BE＞-6）和健康。从三名健康成年男性中分离血小板，并将其用血浆处理 30 分钟。用血栓酶受体激动剂刺激聚集，并通过多电极血小板聚集仪进行测量。将数据归一化为仅用 HEPES Tyrode's（HT）缓冲液处理的血小板。使用 Mann-Whitney U 检验检验血浆处理组与血小板聚集测量值之间的相关性。
与用无休克患者的血浆处理的血小板相比，用休克患者（无论损伤程度如何）的血浆处理的血小板的血栓素刺激聚集明显受损（P=0.002）。相反，用无休克但严重损伤患者的血浆处理的血小板的血栓素刺激聚集增强（P=0.030）。
休克介导的可溶性因子会损害血小板聚集，而组织损伤介导的可溶性因子会增强血小板聚集。对这些可溶性因子的进一步特征描述将支持创伤性凝血病治疗方法的新发展。
