Réti Marienn, Icleanu Andreea-Adela, Várkonyi Andrea, Király Ágnes, Bogsch Luca, Farkas Zita, Reményi Péter, Prohászka Zoltán, Sinkovits György
Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary.
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary.
Thromb Haemost. 2025 Sep 2. doi: 10.1055/a-2685-8118.
In acute immune-mediated TTP (iTTP) caplacizumab therapy has proved to be effective in achieving an early clinical response. However, the discontinuation of caplacizumab therapy before ADAMTS13 activity has at least partially recovered can potentially lead to disease recurrence. Of note, normalization of ADAMTS13 activity was reported to be delayed in caplacizumab-treated patients.To investigate delayed ADAMTS13 normalization and its potential causes.We conducted a retrospective detailed longitudinal investigation of ADAMTS13 activity and anti-ADAMTS13 IgG levels in a single-center cohort of caplacizumab-treated iTTP patients ( = 10). Results were compared to iTTP patients treated according to the standard of care in the same center, without caplacizumab (historical controls, = 28).We observed that ADAMTS13 activity was lower in caplacizumab-treated patients than in historical controls 1 week after therapeutic plasma exchange (TPE) was discontinued upon first clinical response (post-TPE). The difference later gradually decreased and we observed no delay in attaining ADAMTS13 activity thresholds of 20% (partial ADAMTS13 remission, reached in median 26 vs. 25 days after the first TPE session) or higher. However, almost half of the caplacizumab-treated patients needed more than 30 days to achieve partial ADAMTS13 remission. Importantly, we found that the post-TPE anti-ADAMTS13 IgG level correlates with the time until partial ADAMTS13 remission both in caplacizumab-treated and historical control patients, and is a significant predictor of delayed ADAMTS13 normalization.The latter finding has important clinical implications, as it suggests that measuring post-TPE anti-ADAMTS13 IgG levels may help identify patients who need additional immunosuppressive treatment to avoid delayed ADAMTS13 normalization.
在急性免疫介导的血栓性血小板减少性紫癜（iTTP）中，卡泊单抗治疗已被证明在实现早期临床反应方面是有效的。然而，在ADAMTS13活性至少部分恢复之前停用卡泊单抗治疗可能会导致疾病复发。值得注意的是，据报道卡泊单抗治疗的患者中ADAMTS13活性的正常化有所延迟。为了研究ADAMTS13正常化延迟及其潜在原因。我们对单中心队列中接受卡泊单抗治疗的iTTP患者（n = 10）的ADAMTS13活性和抗ADAMTS13 IgG水平进行了回顾性详细纵向研究。将结果与同一中心按照标准治疗方案治疗但未使用卡泊单抗的iTTP患者（历史对照，n = 28）进行比较。我们观察到，在首次临床反应后（治疗性血浆置换后）停用治疗性血浆置换（TPE）1周时，接受卡泊单抗治疗的患者的ADAMTS13活性低于历史对照。差异随后逐渐减小，我们观察到达到20%的ADAMTS13活性阈值（部分ADAMTS13缓解，首次TPE疗程后中位数分别为26天和25天达到）或更高时没有延迟。然而，几乎一半接受卡泊单抗治疗的患者需要超过30天才能实现部分ADAMTS13缓解。重要的是，我们发现治疗性血浆置换后的抗ADAMTS13 IgG水平与接受卡泊单抗治疗的患者和历史对照患者中直至部分ADAMTS13缓解的时间相关，并且是ADAMTS13正常化延迟的重要预测指标。后一发现具有重要的临床意义，因为它表明测量治疗性血浆置换后的抗ADAMTS13 IgG水平可能有助于识别需要额外免疫抑制治疗以避免ADAMTS13正常化延迟的患者。
