The von Willebrand Factor-Cleaving Protease (ADAMTS-13) and the Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)
The von Willebrand Factor-Cleaving Protease (ADAMTS-13) and the Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)
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冯维勒布兰德因子裂解蛋白酶 (ADAMTS-13) 和血栓性血小板减少性紫癜 (TTP) 的诊断
DOI：
10.1159/000083839
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发表时间：
2003
影响因子：
--
通讯作者：
B. Lämmle
中科院分区：
文献类型：
--
作者：
J. K. Kremer Hovinga;J. Studt;B. Lämmle
血栓性血小板减少性紫癜（TTP）是一种危及生命的疾病，其特征是微血管性溶血性贫血和血小板减少，这是微血管血小板凝集的结果，通常伴有缺血性器官功能障碍，如神经系统异常或肾功能不全和发热。直到世纪60年代，TTP仍然是一种几乎普遍致命的疾病。血浆置换疗法（PE）的引入与新鲜冷冻血浆的替代已显着提高急性TTP患者的生存率从不到10%到约80-90%，现在被认为是治疗的选择。血管性血友病因子（VWF）裂解蛋白酶（现称为ADAMTS-13）的严重缺乏阻止了从内皮细胞释放的异常大的VWF多聚体的正常加工，并且假定它们的持续存在是微血管系统中血小板血栓形成的原因，这是急性TTP的病理生理学标志。ADAMTS-13活性<正常值的5%是急性经典TTP的特异性发现。然而，这一发现对TTP临床诊断的敏感性不明确，报告的患病率范围为33 - 100%。今天，两种形式的经典TTP被区分开来。遗传性TTP，也称为Upshaw-Schulman综合征，是由ADAMTS-13基因的复合杂合或纯合突变引起的严重的体质性ADAMTS-13缺陷引起的，患者通常表现为慢性复发过程。获得性或散发性TTP是由抑制ADAMTS-13活性的循环自身抗体引起的。获得性TTP的复发也很常见，约35-50%的第一次发作的幸存者会发生复发。尽管治疗方式有所改进，但由于死亡率和发病率仍然相当高，因此患有TTP急性发作的患者对任何临床医生都构成了挑战。
Thrombotic thrombocytopenic purpura (TTP) is a life threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia as a result of microvascular platelet clumping often accompanied by ischemic organ dysfunctions such as neurological abnormalities or renal insufficiency, and fever. Until the sixties of the 20th century TTP remained an almost universally fatal disorder. The introduction of plasma exchange therapy (PE) with replacement of fresh frozen plasma has dramatically improved the survival of patients with acute TTP from less than 10% to about 80-90% and is now considered the therapy of choice. Severe deficiency of the von Willebrand factor (VWF)-cleaving protease, now denoted as ADAMTS-13, prevents normal processing of unusually large VWF multimers released from endothelial cells and it is assumed that their persistence is responsible for the formation of platelet thrombi in the microvasculature, a pathophysiological hallmark of acute TTP. An ADAMTS-13 activity of <5% of the normal is a specific finding for acute classical TTP. However, the sensitivity of this finding for the clinical diagnosis of TTP is equivocal with reported prevalences ranging from 33 -100%. Today, two forms of classical TTP are distinguished. Hereditary TTP, also known as Upshaw-Schulman syndrome, is caused by severe constitutionalADAMTS-13 deficiency due to compound heterozygous or homozygous mutations of theADAMTS13 gene and patients often present with a chronic relapsing course. The acquired or sporadic form of TTP is caused by circulating autoantibodies inhibiting ADAMTS-13 activity. Relapses are also frequent in acquired TTP occurring in about 35-50% of survivors of a first bout. Despite improved treatment modalities, patients suffering from acute bouts of TTP constitute a challenge for any clinician as mortality and morbidity rates are still considerably high.
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影响因子：
20.3
作者：
Padilla, A;Moake, JL;Dong, JF
通讯作者：
Dong, JF
影响因子：
158.5
作者：
BELL, WR;BRAINE, HG;KICKLER, TS
通讯作者：
KICKLER, TS
DOI：
10.1073/pnas.87.16.6306
发表时间：
1990-08-01
影响因子：
11.1
作者：
DENT, JA;BERKOWITZ, SD;RUGGERI, ZM
通讯作者：
RUGGERI, ZM
影响因子：
20.3
作者：
Dong, JF;Moake, JL;López, JA
通讯作者：
López, JA
影响因子：
158.5
作者：
Tsai, HM;Lian, ECY
通讯作者：
Lian, ECY