静脉血栓栓塞症患者严重出血的促炎和抗炎反应的时间特征：来自 PROPPR 试验的结果。
Temporal profile of the pro- and anti-inflammatory responses to severe hemorrhage in patients with venous thromboembolism: Findings from the PROPPR trial.
机构信息
From the Division of Trauma, Critical Care & Acute Care Surgery, Department of Surgery (B.H.M., M.A.S.), Oregon Health & Science University, Portland, Oregon; Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery (C.E.W., E.E.F.), University of Texas Health Science Center, Houston, Texas; Division of Acute Care Surgery, Department of Surgery (K.I.), University of Southern California, Los Angeles, California; Department of Surgery (M.J.C.), Denver Health Medical Center and the University of Colorado; Denver, Colorado; and Department of Surgery (J.B.H.), University of Alabama at Birmingham, Birmingham, Alabama.
出版信息
J Trauma Acute Care Surg. 2021 May 1;90(5):845-852. doi: 10.1097/TA.0000000000003088.
BACKGROUND
The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE.
STUDY DESIGN
Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance.
RESULTS
Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 β (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation.
CONCLUSION
Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events.
LEVEL OF EVIDENCE
Prognostic, level III.
背景
随机实用血小板和血浆比值（PROPPR）试验表明，15%的出血后患者发生静脉血栓栓塞（VTE），但其机制尚不清楚。由于炎症与高凝状态和血栓形成有关，我们的目标是比较出血性休克后伴有和不伴有 VTE 的患者的时间炎症谱。
研究设计
对 PROPPR 收集的数据进行二次分析。入院后 0 小时、2 小时、4 小时、6 小时、12 小时、24 小时、48 小时和 72 小时采集的血液样本进行 27 个目标细胞因子检测，并比较 VTE（n=83）和非 VTE（n=475）患者。p<0.05 表示差异有统计学意义。
结果
随着时间的推移，两组均表现出促炎介质白细胞介素（IL）-6、IL-8、IL-10、粒细胞集落刺激因子 57、单核细胞趋化蛋白 1 和巨噬细胞炎症蛋白 1β，以及抗炎介质 IL-1ra 和 IL-10 的升高（与入院时相比，p<0.05）。VTE 患者的 IL-6（6-72 小时）和 IL-8（6-24 小时）反应增强，峰值出现在较晚的时间点，而粒细胞集落刺激因子 57（12-24 小时）、单核细胞趋化蛋白 1（6-72 小时）和巨噬细胞炎症蛋白-1β（2-12 小时）的峰值出现在与非 VTE 患者相似的时间点（p<0.05）。两组抗炎反应相似，但 VTE 组抗炎反应高峰后，白细胞介素介导的促炎反应持续升高。VTE（97%）的不良事件发生率高于非 VTE（87%，p=0.009），且与炎症反应升高相关。
结论
出血性休克后发生 VTE 的患者表现出由选择的白细胞介素、趋化因子和糖蛋白细胞因子介导的延长和放大的促炎反应，而抗炎介质不能拮抗这种反应。这种反应与随机分组、损伤严重程度或休克程度无关，但可能与不良事件有关。
证据水平
预后，III 级。
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