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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2685-8118
Stroke, Systemic or Venous Thromboembolism

High anti-ADAMTS13 IgG Levels after Plasma Exchange Predict Delayed ADAMTS13 Normalization in Immune-mediated Thrombotic Thrombocytopenic Purpura

Marienn Réti   *
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Andreea-Adela Icleanu    *
2   Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
3   Research Group for Immunology and Hematology, Semmelweis University - Hungarian Research Network (Office for Supported Research Groups), Budapest, Hungary
,
Andrea Várkonyi
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Ágnes Király
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Luca Bogsch
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Zita Farkas
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Péter Reményi
1   Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest - Institute of Hematology and Infectious Diseases, Budapest, Hungary
,
Zoltán Prohászka
2   Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
3   Research Group for Immunology and Hematology, Semmelweis University - Hungarian Research Network (Office for Supported Research Groups), Budapest, Hungary
,
György Sinkovits 
2   Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
3   Research Group for Immunology and Hematology, Semmelweis University - Hungarian Research Network (Office for Supported Research Groups), Budapest, Hungary
› Institutsangaben
Funding This study was supported by the European Union's Horizon 2021 research and innovation program (under grant agreement No. 101072729) and by the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic program of Semmelweis University, “MOLORKIV” (project No. TKP2021-EGA-24).
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Abstract

Background

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.

Aims

To investigate delayed ADAMTS13 normalization and its potential causes.

Patients/Methods

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 (n = 10). Results were compared to iTTP patients treated according to the standard of care in the same center, without caplacizumab (historical controls, n = 28).

Results

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.

Conclusion

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.

Keywords

ADAMTS13 - autoantibodies - caplacizumab - therapeutic plasma exchange - thrombotic thrombocytopenic purpura

Data Availability Statement

Requests for original data should be submitted to the corresponding author (e-mail: sinkovits.gyorgy@semmelweis.hu).


Authors' Contribution

M.R., Z.P., and G.S,: designed the study; M.R., A.V., Á.K., L.B., Z.F., and P.R.: provided patient samples and related clinical and laboratory data; A.I. and G.S.: performed the experiments; M.R., A.I., and G.S.: analyzed results, prepared the figures, and drafted the manuscript. The manuscript was critically reviewed and the final version was approved by all the authors.


* These authors contributed equally to this study.


Supplementary Material



Publikationsverlauf

Eingereicht: 12. März 2025

Angenommen: 18. Juli 2025

Accepted Manuscript online:
20. August 2025

Artikel online veröffentlicht:
02. September 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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