Bonnez Quintijn, Sakai Kazuya, Vanhoorelbeke Karen
Department of Chemistry, KU Leuven Campus Kulak Kortrijk, 8500 Kortrijk, Belgium.
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 634-8522, Japan.
J Clin Med. 2023 Sep 24;12(19):6169. doi: 10.3390/jcm12196169.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare medical emergency for which a correct and early diagnosis is essential. As a severe deficiency in A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats, member 13 (ADAMTS13) is the underlying pathophysiology, diagnostic strategies require timely monitoring of ADAMTS13 parameters to differentiate TTP from alternative thrombotic microangiopathies (TMAs) and to guide initial patient management. Assays for conventional ADAMTS13 testing focus on the enzyme activity and presence of (inhibitory) anti-ADAMTS13 antibodies to discriminate immune-mediated TTP (iTTP) from congenital TTP and guide patient management. However, diagnosis of iTTP remains challenging when patients present borderline ADAMTS13 activity. Therefore, additional biomarkers would be helpful to support correct clinical judgment. Over the last few years, the evaluation of ADAMTS13 conformation has proven to be a valuable tool to confirm the diagnosis of acute iTTP when ADAMST13 activity is between 10 and 20%. Screening of ADAMTS13 conformation during long-term patient follow-up suggests it is a surrogate marker for undetectable antibodies. Moreover, some non-ADAMTS13 parameters gained notable interest in predicting disease outcome, proposing meticulous follow-up of iTTP patients. This review summarizes non-ADAMTS13 biomarkers for which inclusion in routine clinical testing could largely benefit differential diagnosis and follow-up of iTTP patients.
免疫介导的血栓性血小板减少性紫癜（iTTP）是一种罕见的医疗急症，正确且早期诊断至关重要。由于具有1型血小板反应蛋白基序的解聚素和金属蛋白酶13（ADAMTS13）严重缺乏是其潜在的病理生理学机制，诊断策略需要及时监测ADAMTS13参数，以区分TTP与其他血栓性微血管病（TMA），并指导患者的初始管理。传统ADAMTS13检测的分析方法侧重于酶活性以及（抑制性）抗ADAMTS13抗体的存在，以区分免疫介导的TTP（iTTP）与先天性TTP，并指导患者管理。然而，当患者的ADAMTS13活性处于临界值时，iTTP的诊断仍然具有挑战性。因此，额外的生物标志物将有助于支持正确的临床判断。在过去几年中，当ADAMTS13活性在10%至20%之间时，对ADAMTS13构象的评估已被证明是确诊急性iTTP的有价值工具。在患者长期随访期间对ADAMTS13构象进行筛查表明，它是检测不到抗体的替代标志物。此外，一些非ADAMTS13参数在预测疾病预后方面引起了显著关注，这提示需要对iTTP患者进行细致的随访。本综述总结了非ADAMTS13生物标志物，将其纳入常规临床检测可能会在很大程度上有助于iTTP患者进行鉴别诊断和随访。
