Jin Ming, Casper T Charles, Cataland Spero R, Kennedy Melanie S, Lin Shili, Li Yu J, Wu Haifeng M
Department of Pathology, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Br J Haematol. 2008 May;141(5):651-8. doi: 10.1111/j.1365-2141.2008.07107.x. Epub 2008 Apr 7.
Idiopathic thrombotic thrombocytopenic purpura (TTP) is characterized by frequent recurrences. Effective screening for relapses will enable intervention prior to overt episodes of TTP. The present study used a modified assay to detect ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13) activity as low as 0.5%. This analytical improvement permits adequate measurement of ADAMTS13 activity levels in 97% of remission samples used for statistical modelling. ADAMTS13 activity and ADAMTS13 antibody (IgG) were measured in 157 serial samples prospectively collected from 24 TTP patients during periods of clinical remission. These patients were followed-up quarterly for an average of 23 months, during which time nine episodes of TTP relapse occurred among six patients. Finally, logistic regression modelling was used to define the relationship between ADAMTS13 activity levels (0.5-100%) and the probability of TTP relapses. Our data demonstrated that lower ADAMTS13 activity and younger age were significantly associated with higher risk of relapse in the 3 months after specimens were taken. In contrast, ADAMTS13 antibody IgG levels were not predictive of TTP relapses. Identification of low ADAMTS13 activity during clinical remission as a key risk factor for TTP relapses provides a new screening strategy to identify patients who may benefit from prophylactic therapy prior to disease relapses.
特发性血栓性血小板减少性紫癜（TTP）的特点是频繁复发。有效筛查复发情况将有助于在TTP明显发作之前进行干预。本研究采用一种改良检测方法来检测ADAMTS13（含血小板反应蛋白基序的解聚素和金属蛋白酶13）活性，其低至0.5%。这一分析改进使得能够对用于统计建模的97%的缓解样本中的ADAMTS13活性水平进行充分测量。在临床缓解期从24例TTP患者前瞻性收集的157份系列样本中测量了ADAMTS13活性和ADAMTS13抗体（IgG）。这些患者每季度随访一次，平均随访23个月，在此期间6例患者出现9次TTP复发。最后，采用逻辑回归建模来确定ADAMTS13活性水平（0.5 - 100%）与TTP复发概率之间的关系。我们的数据表明，在采集样本后的3个月内，较低的ADAMTS13活性和较年轻的年龄与较高的复发风险显著相关。相比之下，ADAMTS13抗体IgG水平不能预测TTP复发。将临床缓解期ADAMTS13活性低确定为TTP复发的关键危险因素，为识别可能在疾病复发前从预防性治疗中获益的患者提供了一种新的筛查策略。
