Ganter Michael T, Brohi Karim, Cohen Mitchell J, Shaffer Lisa A, Walsh Mary C, Stahl Gregory L, Pittet Jean-François
Departments of Anesthesia, San Francisco General Hospital, University of California San Francisco, California 94110, USA.
Shock. 2007 Jul;28(1):29-34. doi: 10.1097/shk.0b013e3180342439.
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.
据报道，严重创伤后会发生补体激活。然而，对于创伤后早期补体激活的临床相关性及机制，人们了解甚少。因此，本研究旨在测定补体激活情况，明确损伤严重程度和低灌注的作用，确定主要的激活途径，并明确创伤患者早期补体激活的临床意义。本前瞻性单中心队列研究共纳入208例成年创伤患者。在受伤后30分钟内、进行任何显著的液体复苏之前采集血样。创伤后早期补体（C5b-9）被激活，与损伤严重程度和组织低灌注相关，并与死亡率增加以及急性肺损伤和急性肾衰竭等器官功能衰竭的发生有关。替代途径似乎是创伤后早期主要的补体激活途径。然而，由于C4d与C3a/C5b-9的血浆水平之间存在相关性，经典途径和/或凝集素途径启动了补体激活。最后，在C3a水平较低的患者中，C5b-9水平与凝血酶生成标志物凝血酶原片段1 + 2的血浆水平相关，提示严重创伤后凝血酶可通过不依赖C3的途径额外激活补体。总之，创伤后早期可观察到通过替代途径进行放大的补体激活，且其与损伤严重程度、组织低灌注及更差的临床结局相关。除了经典途径和/或凝集素途径激活补体外，凝血酶生成与补体激活之间还存在独立关联。
