Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Aurora, Colorado.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, Colorado.
Shock. 2023 Jan 1;59(1):12-19. doi: 10.1097/SHK.0000000000002036. Epub 2022 Nov 16.
Background: Severe injury can provoke systemic processes that lead to organ dysfunction, and hemolysis of both native and transfused red blood cells (RBCs) may contribute. Hemolysis can release erythrocyte proteins, such as hemoglobin and arginase-1, the latter with the potential to disrupt arginine metabolism and limit physiologic NO production. We aimed to quantify hemolysis and arginine metabolism in trauma patients and measure association with injury severity, transfusions, and outcomes. Methods: Blood was collected from injured patients at a level I trauma center enrolled in the COMBAT (Control of Major Bleeding After Trauma) trial. Proteomics and metabolomics were performed on plasma fractions through liquid chromatography coupled with mass spectrometry. Abundances of erythrocyte proteins comprising a hemolytic profile as well as haptoglobin, l -arginine, ornithine, and l -citrulline (NO surrogate marker) were analyzed at different timepoints and correlated with transfusions and adverse outcomes. Results: More critically injured patients, nonsurvivors, and those with longer ventilator requirement had higher levels of hemolysis markers with reduced l -arginine and l -citrulline. In logistic regression, elevated hemolysis markers, reduced l -arginine, and reduced l -citrulline were significantly associated with these adverse outcomes. An increased number of blood transfusions were significantly associated with elevated hemolysis markers and reduced l -arginine and l -citrulline independently of New Injury Severity Score and arterial base excess. Conclusions: Severe injury induces intravascular hemolysis, which may mediate postinjury organ dysfunction. In addition to native RBCs, transfused RBCs can lyse and may exacerbate trauma-induced hemolysis. Arginase-1 released from RBCs may contribute to the depletion of l -arginine and the subsequent reduction in the NO necessary to maintain organ perfusion.
严重损伤可引发全身性反应，导致器官功能障碍，而内源性和输注的红细胞（RBC）的溶血可能与此相关。溶血可释放红细胞蛋白，如血红蛋白和精氨酸酶-1，后者可能破坏精氨酸代谢并限制生理一氧化氮（NO）的产生。我们旨在量化创伤患者的溶血和精氨酸代谢，并测量其与损伤严重程度、输血和结局的关系。方法：从参加 COMBAT（创伤后控制大出血）试验的 I 级创伤中心的损伤患者中采集血液。通过液相色谱与质谱联用对血浆部分进行蛋白质组学和代谢组学分析。在不同时间点分析构成溶血谱的红细胞蛋白以及结合珠蛋白、l-精氨酸、瓜氨酸和 l-瓜氨酸（NO 替代标志物）的丰度，并与输血和不良结局相关联。结果：损伤更严重的患者、非幸存者和需要更长时间呼吸机支持的患者具有更高水平的溶血标志物，同时 l-精氨酸和 l-瓜氨酸水平降低。在逻辑回归中，升高的溶血标志物、降低的 l-精氨酸和降低的 l-瓜氨酸与这些不良结局显著相关。输血次数的增加与升高的溶血标志物以及降低的 l-精氨酸和 l-瓜氨酸显著相关，与新损伤严重程度评分和动脉碱剩余无关。结论：严重损伤可导致血管内溶血，这可能介导损伤后的器官功能障碍。除了内源性 RBC 外，输注的 RBC 也可能发生溶血，从而加剧创伤引起的溶血。从 RBC 释放的精氨酸酶-1可能导致 l-精氨酸的消耗减少以及维持器官灌注所需的 NO 减少。
