Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Katholieke Universiteit Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Katholieke Universiteit Leuven Campus Kulak Kortrijk, Kortrijk, Belgium; Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
J Thromb Haemost. 2024 Feb;22(2):493-502. doi: 10.1016/j.jtha.2023.10.014. Epub 2023 Oct 20.
ADAMTS-13 adopts an open conformation in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in acute phase while being closed in healthy donors. We reported that a substantial number of patients with iTTP in remission with restored ADAMTS-13 activity (>50%) still had an open ADAMTS-13 conformation, although a closed conformation is expected given the extent of remission.
To investigate whether open ADAMTS-13, represented by a conformation index >0.5, is associated with a risk of earlier ADAMTS-13 and/or clinical relapse.
We collected follow-up data (ADAMTS-13 parameters, ADAMTS-13 and clinical relapse, and treatment) from 81 patients with iTTP in remission with ADAMTS-13 activity >50%.
During follow-up, 19 ADAMTS-13 and 10 clinical relapses were reported (median follow-up period, 20 months). First, open or closed ADAMTS-13 conformation was dichotomized based on the 0.5 conformation index cutoff. Open ADAMTS-13 (conformation index, >0.5) was not identified as a risk factor for ADAMTS-13 and clinical relapse (log-rank test and Cox regression model). In contrast, by identifying the optimal conformation index cutoff for relapse prediction, using classification and regression tree analysis, a conformation index >0.645 and >0.835 was shown to be a risk factor for ADAMTS-13 relapse (hazard ratio, 3.3; 95% CI, 1.3-8.3; P = .01) and clinical relapse (hazard ratio, 4.4; 95% CI, 1.3-15.3; P = .02), respectively.
Patients with open ADAMTS-13 with a conformation index >0.645 and >0.835 have a >3- and >4-fold higher risk of earlier ADAMTS-13 and clinical relapse, respectively. Hence, ADAMTS-13 conformation index could be used to complement ADAMTS-13 activity monitoring to timely notice ADAMTS-13 relapse and prevent clinical relapse.
ADAMTS-13 在免疫介导性血栓性血小板减少性紫癜（iTTP）急性期呈开放构象，而在健康供体中呈关闭构象。我们报道，相当数量的 iTTP 缓解患者的 ADAMTS-13 活性恢复（>50%），但仍存在大量的 ADAMTS-13 开放构象，尽管考虑到缓解程度，应存在关闭构象。
研究 ADAMTS-13 开放构象（构象指数>0.5）是否与 ADAMTS-13 复发和/或临床复发的风险相关。
我们收集了 81 例 ADAMTS-13 活性>50%的 iTTP 缓解患者的随访数据（ADAMTS-13 参数、ADAMTS-13 和临床复发以及治疗情况）。
在随访期间，报告了 19 例 ADAMTS-13 复发和 10 例临床复发（中位随访时间为 20 个月）。首先，根据 0.5 构象指数截断值，将 ADAMTS-13 开放或关闭构象进行二分法。ADAMTS-13 开放（构象指数>0.5）未被确定为 ADAMTS-13 和临床复发的危险因素（对数秩检验和 Cox 回归模型）。相反，通过使用分类回归树分析确定预测复发的最佳构象指数截断值，发现构象指数>0.645 和>0.835 是 ADAMTS-13 复发（危险比，3.3；95%CI，1.3-8.3；P=0.01）和临床复发（危险比，4.4；95%CI，1.3-15.3；P=0.02）的危险因素。
构象指数>0.645 和>0.835 的 ADAMTS-13 开放患者发生 ADAMTS-13 和临床复发的风险分别增加 3 倍和 4 倍以上。因此，ADAMTS-13 构象指数可用于补充 ADAMTS-13 活性监测，及时发现 ADAMTS-13 复发并预防临床复发。
