- 期刊
Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome: Pathogenesis and Therapy
血栓性血小板減少紫斑症－溶血性尿毒症候群：疾病發生論和血漿置換術治療
摘要
血栓性血小板減少紫斑症（TTP）和溶血性尿毒症候群（HUS）是罕見又密切相關的疾病，具有不同嚴重度的臨床相似性，特點為血小板減少和微血管病變溶血性貧血。血栓性血小板減少紫斑症，傳統上將其描述為五種徵候為一組的表現，即血小板減少、微血管病變溶血性貧血、神經的症狀、腎臟的侵犯和發燒。溶血性尿毒症候群，主要侵犯小孩，呈現血小板減少、微血管病變溶血性貧血和以腎功能不全為主的臨床表現。臨床上有各種不同的命名來表述這些相似但結合不同程度腎臟和神經症狀的症候群。因為無確定的疾病發生論的證據來支持各種不同疾病類別的分辨，因此有學者將這些不同疾病類別統稱為TTP-HUS。近10年來，學者們對這些異常類別的疾病發生論有所論述：一，大部分先天性和後天性血栓性血小板減少紫斑症病人的血循環中可發現ADAMTS13嚴重缺乏，此導致von Villebran factor調解缺陷；二，許多非典型溶血性尿毒症候群的病人與補體替代路徑調解異常有關，乃補體蛋白基因突變，包括C3，因子H，B，I及胞膜補體輔因子蛋白。這些進展，及對Shiga毒素和下痢相關的溶血性尿毒症候群之間關係的相當認知，提供了我們對這些多變的疾病過程更多的了解，也提供了TTP-HUS診斷和治療的進一步方向。假如未治療，血栓性血小板減少紫斑症的病程將快速進行；不可逆腎衰竭、進行性神經異常、心肌缺血及死亡是常見的後果。血漿置換術具有高度反應率，因此，當病人出現二位組的徵候時，即血小板減少和微血管病變溶血性貧血，就應起動血漿置換術。
關鍵字
無資料並列摘要
Thrombotic thrombocytopenia purpura (TTP) and hemolytic uremia syndrome (HUS) are rare and closed-related disorders with similar clinical features. They are characterized by thrombocytopenia and microangiopathic hemolytic anemia in different severity. TTP was conventionally described as a pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal involvement and fever. HUS affects mainly children and presents with microangiopathic hemolytic anemia, thrombocytopenia and a clinical picture dominated by renal insufficiency. Clinically, various denominations have been used to describe these similar syndromes with variable combinations of neurologic and renal manifestations. Because of without definitive pathogenetic evidence to support a clear distinction among the various clinical entities, some given such disorders the generic term TTP-HUS. In a recent decade, the pathogenesis of those disorders have been described: First, defective regulation of von Willebrand factor activity by a severe deficiency of A Disintegrin and Metalloprotease with ThromboSpondin, type I repeat, member 13 (ADAMTS13) is found in most patients with congenital and acquired idiopathic TTP. Second, mutations in the genes for complement proteins, including Complement 3, factor H, B and I, and membrane cofactor protein are associated with disregulation of alternative complement pathway in many patients with Atypical HUS. These advances, along with well-known association between Shiga toxins and Diarrhea positive HUS (D^+ HUS), provide the better understanding of variable disease processes and the further directions of diagnosis and treatment in TTP-HUS. TTP in adult typically follow a progressive course, irreversible renal failure, progressive neurologic deterioration, cardiac ischemia, and death are common outcome. Plasma exchange is associated with a high response rate, therefore, aggressive plasma exchange should be initiated in all patients as soon as the clinical dyad of microangiopathic hemolytic anemia & thrombocytopenia present.