Levin M, Eley B S, Louis J, Cohen H, Young L, Heyderman R S
Department of Paediatrics, St. Mary's Hospital Medical School, London, United Kingdom.
J Pediatr. 1995 Sep;127(3):355-63. doi: 10.1016/s0022-3476(95)70063-3.
To determine the mechanism responsible for idiopathic purpura fulminans, we investigated the procoagulant and anticoagulant pathways in five consecutive patients, four after varicella, and the fifth after a nonspecific infection.
Procoagulant and anticoagulant factors, including protein C, protein S, and antithrombin III, were measured by quantitative or functional assays. Anti-protein S autoantibodies were identified by dot blotting and Western blotting, and quantified serially by enzyme-linked immunosorbent assay. Clinical and laboratory data were collated retrospectively.
In each case the disease began 7 to 10 days after the onset of the precipitating infection, with rapidly progressive purpura leading to extensive areas of skin necrosis. The illness was complicated by impaired perfusion of limbs or digits (two patients), peripheral gangrene resulting in an above-knee amputation (one patient), and major organ dysfunction caused by thromboembolic phenomena involving the lungs (two patients), the heart (one patient), or the kidneys (one patient). Protein S levels were virtually undetectable at the time of admission and failed to respond to infusions of fresh frozen plasma, despite correction of other procoagulant and anticoagulant factors. All five children had anti-protein S IgM and IgG autoantibodies, which persisted for less than 3 months after admission. Decline in the anti-protein S IgG antibody concentration was associated with normalization of the plasma protein S levels.
Autoimmune protein S deficiency may be a common mechanism causing postinfectious idiopathic purpura fulminans. Recognition of the pathophysiologic mechanism may provide a rational basis for treatment. Immediate heparinization, infusions of fresh frozen plasma, and, in cases complicated by major vessel thrombosis, the use of tissue-type plasminogen activator may limit thromboembolic complications.
为确定暴发性特发性紫癜的发病机制，我们对连续5例患者的促凝血和抗凝血途径进行了研究，其中4例在水痘后发病，第5例在非特异性感染后发病。
通过定量或功能测定法检测促凝血和抗凝血因子，包括蛋白C、蛋白S和抗凝血酶III。通过斑点印迹法和蛋白质印迹法鉴定抗蛋白S自身抗体，并通过酶联免疫吸附测定法进行连续定量。对临床和实验室数据进行回顾性整理。
在每例患者中，疾病均在诱发感染发病后7至10天开始，伴有迅速进展的紫癜，导致大面积皮肤坏死。病情并发肢体或指（趾）灌注受损（2例患者）、外周坏疽导致膝上截肢（1例患者），以及由涉及肺部（2例患者）、心脏（1例患者）或肾脏（1例患者）的血栓栓塞现象引起的主要器官功能障碍。入院时蛋白S水平几乎检测不到，尽管其他促凝血和抗凝血因子已得到纠正，但对输注新鲜冷冻血浆无反应。所有5名儿童均有抗蛋白S IgM和IgG自身抗体，入院后持续时间不到3个月。抗蛋白S IgG抗体浓度的下降与血浆蛋白S水平的正常化相关。
自身免疫性蛋白S缺乏可能是导致感染后暴发性特发性紫癜的常见机制。认识其病理生理机制可为治疗提供合理依据。立即进行肝素化、输注新鲜冷冻血浆，以及在并发大血管血栓形成的病例中使用组织型纤溶酶原激活剂，可能会限制血栓栓塞并发症。
