COMPLEMENT ACTIVATION IN TRAUMA PATIENTS ALTERS PLATELET FUNCTION
COMPLEMENT ACTIVATION IN TRAUMA PATIENTS ALTERS PLATELET FUNCTION
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DOI：
10.1097/shk.0000000000000675
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发表时间：
2016-09-01
期刊：
影响因子：
3.1
通讯作者：
Tsokos, George C.
中科院分区：
文献类型：
--
作者：
Atefi, Gelareh;Aisiku, Omozuanvbo;Tsokos, George C.
创伤仍然是平民和军警死亡的主要原因。创伤性凝血病是一个复杂的过程，涉及炎症、凝血和血小板功能障碍。目前尚不清楚补体的激活是否与创伤相关凝血病的表达有关，而补体的激活在创伤患者中总是发生。我们设计了一项前瞻性研究，我们招募了40名创伤患者和30名健康的捐赠者，他们刚到BIDMC急诊科。健康个体的血小板与创伤患者的血清一起孵育，用聚集法测定其对凝血酶受体激活肽的反应性。用流式细胞术测定创伤患者血小板上的补体沉积。正常血小板在与创伤血清孵育后表现出低活性，即使暴露于创伤血清导致激动剂诱导的钙通量增加。血清中补体的消耗进一步阻断了低活性血小板的活化。相反，补体活化增加血小板聚集。创伤患者的血小板表面C3a和C4d含量明显高于对照组。补体（C4d, C3a）的消耗逆转了创伤血清增加受体激动剂诱导的供体血小板钙通量的能力。我们的数据表明补体增强血小板聚集。尽管其补体含量，创伤血清使血小板活性降低，补体耗竭进一步阻断活性降低的血小板的活化。创伤血清诱导的血小板激活缺陷远不是受体激活，因为激动剂诱导的Ca2+通量在创伤血清中由于补体沉积而升高。
Trauma remains the main cause of death for both civilians and those in uniform. Trauma-associated coagulopathy is a complex process involving inflammation, coagulation, and platelet dysfunction. It is unknown whether activation of complement, which occurs invariably in trauma patients, is involved in the expression of trauma-associated coagulopathy. We designed a prospective study in which we enrolled 40 trauma patients and 30 healthy donors upon arrival to the emergency department of BIDMC. Platelets from healthy individuals were incubated with sera from trauma patients and their responsiveness to a thrombin receptor-activating peptide was measured using aggregometry. Complement deposition on platelets from trauma patients was measured by flow cytometry. Normal platelets displayed hypoactivity after incubation with trauma sera even though exposure to trauma sera resulted in increased agonist-induced calcium flux. Depletion of complement from sera further blocked activation of hypoactive platelets. Conversely, complement activation increased aggregation of platelets. Platelets from trauma patients were found to have significantly higher amounts of C3a and C4d on their surface compared with platelets from controls. Depletion of complement (C4d, C3a) reversed the ability of trauma sera to augment agonist-induced calcium flux in donor platelets. Our data indicate that complement enhances platelet aggregation. Despite its complement content, trauma sera render platelets hypoactive and complement depletion further blocks activation of hypoactive platelets. The defect in platelet activation induced by trauma sera is distal to receptor activation since agonist-induced Ca2+ flux is elevated in the presence of trauma sera owing to complement deposition.