Dysfunction of endothelial protein C activation in severe meningococcal sepsis.
Dysfunction of endothelial protein C activation in severe meningococcal sepsis.
复制标题
DOI：
10.1056/nejm200108093450603
复制
发表时间：
2001-08-09
影响因子：
158.5
通讯作者：
Heyderman, RS
中科院分区：
文献类型：
--
作者：
Faust, SN;Levin, M;Heyderman, RS
背景资料：蛋白C抗凝途径的损伤对于脓毒症相关血栓形成和脑膜炎球菌血症中暴发性紫癜的发展至关重要。我们研究了血栓调节蛋白和内皮细胞蛋白C受体在患有严重脑膜炎球菌血症和紫癜性或点状病变的儿童真皮微血管中的表达。我们评估了21例脑膜炎球菌败血症患儿紫癜性病变活检标本中内皮的完整性、血栓调节蛋白和内皮蛋白C受体的表达结果：脑膜炎球菌脓毒症患者的内皮血栓调节蛋白和内皮蛋白C受体的表达低于对照组，无论是在血栓形成的血管还是在无血栓形成的血管中。在电子显微镜检查中，血栓形成和非血栓形成血管中的内皮细胞通常是完整的。脑膜炎球菌败血症患儿的血浆血栓调节蛋白水平（中位数，6.4 ng/L）高于对照组（中位数，3.6 ng/L; P=0.002）。血浆蛋白C抗原、蛋白S抗原和抗凝血酶抗原水平均低于对照组。在两个未活化的蛋白C浓缩物治疗的患者中，活化蛋白C是无法检测到的入院时，血浆水平仍然low.Conclusions：在严重的脑膜炎球菌败血症，蛋白C活化受损，这一发现与下调内皮血栓调节蛋白-内皮蛋白C受体途径一致。（N Engl J Med 2001;345：408-16.）版权所有（C）2001马萨诸塞州医学会。
Background: Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions.Methods: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens.Results: The expression of endothelial thrombomodulin and of the endothelial protein C receptor was lower in the patients with meningococcal sepsis than in the controls, both in vessels with thrombosis and in vessels without thrombosis. On electron microscopical examination, the endothelial cells were generally intact in both thrombosed and nonthrombosed vessels. Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002). Plasma levels of protein C antigen, protein S antigen, and antithrombin antigen were lower than those in the controls. In two patients treated with unactivated protein C concentrate, activated protein C was undetectable at the time of admission, and plasma levels remained low.Conclusions: In severe meningococcal sepsis, protein C activation is impaired, a finding consistent with down-regulation of the endothelial thrombomodulin-endothelial protein C receptor pathway. (N Engl J Med 2001;345:408-16.) Copyright (C) 2001 Massachusetts Medical Society.