Clinical presentation and treatment of thrombotic thrombocytopenic purpura - analysis of recent diagnostic and therapeutic methods
DOI:
https://doi.org/10.12775/JEHS.2025.79.57872Keywords
thrombotic thrombocytopenic purpura, thrombocytopenia, ADAMTS13Abstract
Introduction
Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disease caused by reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) activity. This disease can lead to a variety of symptoms and be difficult to diagnose. Correct diagnosis is very important to reduce mortality and initiate appropriate treatment. New treatment methods may offer better chances of survival from this potentially fatal disease.
Aim of the study
The aim of the article was to evaluation of different diagnostic pathways and the effectiveness of treatment of thrombotic thrombocytopenic purpura. Drawing the attention of the medical community to the discussed issue. Highlighting the importance of the issue due to the high mortality rate in the absence of treatment.
Materials and methods
The article was prepared by analyzing multiple databases, including PubMed, Google Scholar, and Elsevier covering the period from 2018 to 2024.
Conclusion
Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease, especially if appropriate treatment is not initiated. There is need a special attention to TTP, as treatment needs to begin even before a definitive diagnosis is established, due to the lengthy wait for laboratory results. Although modern biological drugs are available, further research is needed to streamline treatment methods and provide new therapeutic opportunities.
References
1. Du, P., Cristarella, T., Goyer, C., & Moride, Y. (2024). A Systematic Review of the
Epidemiology and Disease Burden of Congenital and Immune-Mediated Thrombotic
Thrombocytopenic Purpura. In Journal of Blood Medicine (Vol. 15, pp. 363–386). Dove
Medical Press Ltd. https://doi.org/10.2147/JBM.S464365
2. Matsumoto, M., Miyakawa, Y., Kokame, K., Ueda, Y., Wada, H., Higasa, S., Yagi, H.,
Ogawa, Y., Sakai, K., Miyata, T., Morishita, E., & Fujimura, Y. (2023). Diagnostic and
treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023.
International Journal of Hematology, 118(5), 529–546.
https://doi.org/10.1007/s12185-023-03657-0
3. Zheng, X. L., Vesely, S. K., Cataland, S. R., Coppo, P., Geldziler, B., Iorio, A.,
Matsumoto, M., Mustafa, R. A., Pai, M., Rock, G., Russell, L., Tarawneh, R., Valdes, J.,
& Peyvandi, F. (2020). ISTH guidelines for the diagnosis of thrombotic
thrombocytopenic purpura. Journal of Thrombosis and Haemostasis, 18(10), 2486–2495.
https://doi.org/10.1111/jth.15006
4. Du, P., Cristarella, T., Goyer, C., & Moride, Y. (2024). A Systematic Review of the
Epidemiology and Disease Burden of Congenital and Immune-Mediated Thrombotic
Thrombocytopenic Purpura. In Journal of Blood Medicine (Vol. 15, pp. 363–386). Dove
Medical Press Ltd. https://doi.org/10.2147/JBM.S464365
5. Selvakumar, S., Liu, A., & Chaturvedi, S. (2023). Immune thrombotic thrombocytopenic
purpura: Spotlight on long-term outcomes and survivorship. In Frontiers in Medicine
(Vol. 10). Frontiers Media S.A. https://doi.org/10.3389/fmed.2023.1137019
6. Adeyemi, A., Razakariasa, F., Chiorean, A., & de Passos Sousa, R. (2022).
Epidemiology, treatment patterns, clinical outcomes, and disease burden among patients
with immune-mediated thrombotic thrombocytopenic purpura in the United States.
Research and Practice in Thrombosis and Haemostasis, 6(6).
https://doi.org/10.1002/rth2.12802
7. George, J. N. (2022). Hereditary thrombotic thrombocytopenic purpura: The risk for
death at birth. In Research and Practice in Thrombosis and Haemostasis (Vol. 6, Issue 8).
John Wiley and Sons Inc. https://doi.org/10.1002/rth2.12840
8. Chiasakul, T., & Cuker, A. (n.d.). Clinical and laboratory diagnosis of TTP: an
integrated approach. https://doi.org/10.1182/asheducation-2018.1.530
9. Karsenty, C. L., Kirk, S. E., Helber, H. L., Esquilin, J. M., Despotovic, J. M., & Grimes,
A. B. (2022). Molecular Diagnosis Is Vital to the Accurate Classification and
Management of Thrombotic Thrombocytopenic Purpura in Children. Frontiers in
Immunology, 13. https://doi.org/10.3389/fimmu.2022.836960
10. Lämmle, B. (2023). A third form of thrombotic thrombocytopenic purpura? In
Haematologica (Vol. 108, Issue 2, pp. 299–300). Ferrata Storti Foundation.
https://doi.org/10.3324/haematol.2022.281095
11. Shah, S., & Verma, P. (2023). Pregnancy-Related Acute Kidney Injury: Do We Know
What to Do? In Nephron (Vol. 147, Issue 1, pp. 35–38). S. Karger AG.
https://doi.org/10.1159/000525492
12. Beltrami-Moreira, M., & DeSancho, M. T. (2022). Delayed diagnosis of congenital
thrombotic thrombocytopenic purpura in a patient with recurrent strokes. Journal of
Thrombosis and Thrombolysis, 53(3), 734–738.
https://doi.org/10.1007/s11239-021-02629-7
13. DeYoung, V., Singh, K., & Kretz, C. A. (2022). Mechanisms of ADAMTS13 regulation.
In Journal of Thrombosis and Haemostasis (Vol. 20, Issue 12, pp. 2722–2732). John
Wiley and Sons Inc. https://doi.org/10.1111/jth.15873
14. Scully, M., Antun, A., Cataland, S. R., Coppo, P., Dossier, C., Biebuyck, N., Hassenpflug,
W.-A., Kentouche, K., Knöbl, P., Kremer Hovinga, J. A., López-Fernández, M. F.,
Matsumoto, M., Ortel, T. L., Windyga, J., Bhattacharya, I., Cronin, M., Li, H., Mellgĺrd,
B., Patel, M., … Wang, L. T. (2024). Recombinant ADAMTS13 in Congenital
Thrombotic Thrombocytopenic Purpura. New England Journal of Medicine, 390(17),
1584–1596. https://doi.org/10.1056/nejmoa2314793
15. Bonnez, Q., Sakai, K., & Vanhoorelbeke, K. (2023). ADAMTS13 and Non-ADAMTS13
Biomarkers in Immune-Mediated Thrombotic Thrombocytopenic Purpura. In Journal of
Clinical Medicine (Vol. 12, Issue 19). Multidisciplinary Digital Publishing Institute
(MDPI). https://doi.org/10.3390/jcm12196169
16. Dainese, C., Valeri, F., Bruno, B., & Borchiellini, A. (2023). Anti-ADAMTS13
Autoantibodies: From Pathophysiology to Prognostic Impact—A Review for Clinicians.
In Journal of Clinical Medicine (Vol. 12, Issue 17). Multidisciplinary Digital Publishing
Institute (MDPI). https://doi.org/10.3390/jcm12175630
17. Halkidis, K., & Zheng, X. L. (2022). ADAMTS13 conformations and mechanism of
inhibition in immune thrombotic thrombocytopenic purpura. In Journal of Thrombosis
and Haemostasis (Vol. 20, Issue 10, pp. 2197–2203). John Wiley and Sons Inc.
https://doi.org/10.1111/jth.15822
18. Coppo, P., Cuker, A., & George, J. N. (2019). Thrombotic thrombocytopenic purpura:
Toward targeted therapy and precision medicine. In Research and Practice in Thrombosis
and Haemostasis (Vol. 3, Issue 1, pp. 26–37). Blackwell Publishing Ltd.
https://doi.org/10.1002/rth2.12160
19. Staley, E. M., Cao, W., Pham, H. P., Kim, C. H., Kocher, N. K., Zheng, L., Gangaraju, R.,
Lorenz, R. G., Williams, L. A., Marques, M. B., & Zheng, X. L. (2019). Clinical factors
and biomarkers predict outcome in patients with immune-mediated thrombotic
thrombocytopenic purpura. Haematologica, 104(1), 166–175.
https://doi.org/10.3324/haematol.2018.198275
20. Watanabe, A., Shiseki, M., Oishi, M., Kobayashi, M., Oshima, S., Osanai, S., Ryuzaki,
M., Izuka, Y., Tanaka, N., Ishiyama, M., Shinohara, A., Kazama, H., Hagiwara, S.,
Yoshinaga, K., & Tanaka, J. (2021). Successful Rituximab treatment in thrombotic
thrombocytopenic purpura patients complicated by other autoimmune disorders: Two
case reports. Internal Medicine, 60(17), 2859–2862.
https://doi.org/10.2169/internalmedicine.6387-20
21. Scully, M., Cataland, S. R., Peyvandi, F., Coppo, P., Knöbl, P., Kremer Hovinga, J. A.,
Metjian, A., de la Rubia, J., Pavenski, K., Callewaert, F., Biswas, D., de Winter, H., &
Zeldin, R. K. (2019). Caplacizumab Treatment for Acquired Thrombotic
Thrombocytopenic Purpura. New England Journal of Medicine, 380(4), 335–346.
https://doi.org/10.1056/nejmoa1806311
22. Graça, N. A. G., Joly, B. S., Voorberg, J., Vanhoorelbeke, K., Béranger, N., Veyradier, A.,
& Coppo, P. (2022). TTP: From empiricism for an enigmatic disease to targeted
molecular therapies. In British Journal of Haematology (Vol. 197, Issue 2, pp. 156–170).
John Wiley and Sons Inc. https://doi.org/10.1111/bjh.18040
23. Mazepa, M. A., Masias, C., & Chaturvedi, S. (2019). How targeted therapy disrupts the
treatment paradigm for acquired TTP: the risks, benefits, and unknowns.
24. Liu-Chen, S., Connolly, B., Cheng, L., Subramanian, R. R., & Han, Z. (2018). MRNA
treatment produces sustained expression of enzymatically active human ADAMTS13 in
mice. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-26298-4
25. Taylor, A., Keogh, L., Dickens, E., Dutt, T., Grainger, J., Gregory, R., Mapplebeck, C.,
Richards, M., Stokley, S., Salta, S., Taylor, T., & Scully, M. (2024). Caplacizumab in
pediatric immune thrombotic thrombocytopenic purpura: the UK TTP Registry
experience. Blood Advances, 8(17), 4563–4567.
https://doi.org/10.1182/bloodadvances.2024013488
26. Lee, H. T., Park, U. B., Jeong, T. J., Gu, N., Lee, S. H., Kim, Y., & Heo, Y. S. (2021).
High-resolution structure of the vWF A1 domain in complex with caplacizumab, the first
nanobody-based medicine for treating acquired TTP. Biochemical and Biophysical
Research Communications, 567, 49–55. https://doi.org/10.1016/j.bbrc.2021.06.030
27. Mazepa, M. A., Raval, J. S., Brecher, M. E., & Park, Y. A. (2018). Treatment of acquired
Thrombotic Thrombocytopenic Purpura in the U.S. remains heterogeneous: Current and
future points of clinical equipoise. Journal of Clinical Apheresis, 33(3), 291–296.
https://doi.org/10.1002/jca.21600
28. Taylor, A., Vendramin, C., Oosterholt, S., della Pasqua, O., & Scully, M. (2019).
Pharmacokinetics of plasma infusion in congenital thrombotic thrombocytopenic
purpura. Journal of Thrombosis and Haemostasis, 17(1), 88–98.
https://doi.org/10.1111/jth.14345
29. Sukumar, S., Lämmle, B., & Cataland, S. R. (2021). Thrombotic thrombocytopenic
purpura: Pathophysiology, diagnosis, and management. In Journal of Clinical Medicine
(Vol. 10, Issue 3, pp. 1–24). MDPI. https://doi.org/10.3390/jcm10030536
30. Coppo, P., & Veyradier, A. (2020). TTP in the setting of pregnancy: The story still has to
be written. In Journal of Thrombosis and Haemostasis (Vol. 18, Issue 10, pp.
2775–2777). Blackwell Publishing Ltd. https://doi.org/10.1111/jth.15030
31. Fakhouri, F., Scully, M., Provôt, F., Blasco, M., Coppo, P., Noris, M., Paizis, K., &
Kavanagh, D. (n.d.).Management of thrombotic microangiopathy in pregnancy and
postpartum: report from an international working group DOI:
10.1182/blood.2020005221
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