Role of the alternative pathway in the early complement activation following major trauma
Role of the alternative pathway in the early complement activation following major trauma
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DOI：
10.1097/shk.0b013e3180342439
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发表时间：
2007-07-01
期刊：
影响因子：
3.1
通讯作者：
Pittet, Jean-Frangois
中科院分区：
文献类型：
--
作者：
Ganter, Michael T.;Brohi, Karim;Pittet, Jean-Frangois
据报道，严重创伤后补体激活。然而，人们对创伤后早期补体激活的临床相关性和机制知之甚少。因此，本研究的目的是测量补体激活，确定损伤严重程度和灌注不足的作用，确定主要激活途径，并确定创伤患者早期补体激活的临床意义。共有 208 名成年创伤患者参加了这项针对重大创伤患者的前瞻性单中心队列研究。受伤后 30 分钟内采集血样，然后进行任何重要的液体复苏。补体 (C5b-9) 在创伤后早期被激活，与损伤严重程度和组织灌注不足相关，并与死亡率增加以及急性肺损伤和急性肾衰竭等器官衰竭的发生有关。替代途径似乎是创伤后早期主要的激活补体途径。然而，由于 C4d 和 C3a/C5b-9 血浆水平之间的相关性，经典和/或凝集素途径启动了补体激活。最后，在 C3a 水平低的患者中，C5b-9 水平与凝血酶原片段 1 + 2 的血浆水平相关，凝血酶原片段 1 + 2 是凝血酶生成的标志物，表明严重创伤后凝血酶会额外激活不依赖于 C3 的补体。总之，在创伤后早期观察到补体通过旁路途径放大而激活，并且与损伤严重程度、组织灌注不足和较差的临床结果相关。除了经典和/或凝集素途径的补体激活之外，凝血酶生成和补体激活之间存在独立的关联。
Complement activation has been reported after major trauma. However, little is known about the clinical relevance and the mechanisms of complement activation early after trauma. Therefore, the aim of this study was to measure complement activation, to identify the roles of injury severity and hypoperfusion, to determine the predominant activated pathway, and to identify the clinical significance of early complement activation in trauma patients. A total of 208 adult trauma patients were enrolled in this prospective single-center cohort study of major trauma patients. Blood samples were obtained within 30 min after injury before any significant fluid resuscitation. Complement (C5b-9) was activated early after trauma, correlated with injury severity and tissue hypoperfusion, and was associated with increased mortality rate and with the development of organ failure such as acute lung injury and acute renal failure. The alternative pathway seems to be the predominant activated complement pathway early after trauma. However, the classical and/or the lectin pathway initiated complement activation because of the correlation between plasma levels of C4d and C3a/C5b-9. Finally, in patients with low C3a levels, C5b-9 levels correlated with plasma levels of prothrombin fragments 1 + 2, a marker of thrombin generation, suggesting additional C3-independent complement activation by thrombin after severe trauma. In summary, complement activation via its amplification by the alternative pathway is observed early after trauma and correlates with injury severity, tissue hypoperfusion, and worse clinical outcomes. Besides complement activation by the classical and/or lectin pathways, there is an independent association between thrombin generation and complement activation.