Clinical and laboratory diagnosis of TTP: an integrated approach
Clinical and laboratory diagnosis of TTP: an integrated approach
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DOI：
10.1182/asheducation-2018.1.530
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发表时间：
2018-11-01
影响因子：
3
通讯作者：
Cuker, Adam
中科院分区：
文献类型：
--
作者：
Chiasakul, Thita;Cuker, Adam
血栓性血小板减少性紫癜（TTP）是一种罕见的、危及生命的疾病，其发病率约为每年每百万人中有2人。其特征在于血管性血友病裂解蛋白酶ADAMTS13（一种具有1型血小板反应蛋白基序的去整合素和金属蛋白酶，成员13）严重缺乏，导致微血管系统中形成富含血小板的血栓。及时开始适当的治疗，特别是血浆置换，可能会挽救生命。TTP的诊断具有挑战性，因为其临床表现多样，与其他血栓性微血管病的临床表现重叠，以及ADAMTS13检测的可用性有限。临床预测评分已被开发用于估计严重ADAMTS13缺陷的预测试概率，并可用作临床判断的辅助工具，以指导初始管理决策。ADAMTS13活性水平低于10%支持在适当的临床背景下诊断TTP，但许多中心不提供内部检测，必须将检测结果发送到参考实验室，周转时间为几天。在这种情况下，必须在没有实验室检测的情况下作出初步管理决定。在TTP患者中，抑制物试验可能有助于区分免疫介导的先天性UP。在这篇文章中，我们回顾了TTP的流行病学，自然史和临床表现，以及UP的实验室检测，包括ADAMTS13活性和抑制剂检测。我们还描述了一种基于证据的方法来评估疑似TTP患者，该方法整合了临床和实验室评估。
Thrombotic thrombocytopenia purpura (TTP) is a rare, life-threatening disease with an incidence of approximately 2 persons per million per year. It is characterized by severe deficiency of the von Willebrand cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), leading to formation of platelet-rich thrombi in the microvasculature. Prompt initiation of appropriate therapy, particularly plasma exchange, may be life-saving. Diagnosis of TTP is challenging because of its diverse clinical manifestations, overlap in clinical presentation with other thrombotic microangiopathies, and limited availability of ADAMTS13 testing. Clinical prediction scores have been developed to estimate the pretest probability of severe ADAMTS13 deficiency and may be used as an adjunct to clinical judgment to guide initial management decisions. An ADAMTS13 activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts, but many centers do not offer testing in-house and must send out the test to a reference laboratory with a turnaround time of several days. In such instances, initial management decisions must be made without the benefit of laboratory testing. In patients with TTP, inhibitor tests may be useful for distinguishing immune-mediated from congenital UP. In this article, we review the epidemiology, natural history, and clinical presentation of TTP and laboratory assays for UP including ADAMTS13 activity and inhibitor assays. We also describe an evidence-based approach to the evaluation of a patient with suspected TTP that integrates clinical and laboratory assessment.