Avoid common mistakes on your manuscript.
To the Editor,
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening immune-mediated disease caused by autoantibodies directed against the von Willebrand (vWF) cleaving protease ADAMTS13. The resulting severe deficiency of ADAMTS13 is responsible for a clinical picture that comprises hemolysis, thrombocytopenia, and widespread organ disfunction [1]. The traditional approach to aTTP used to combine plasma exchange (PEX) with immunosuppressants, but mortality rate remained remarkable (up to 10–15%) in refractory patients [2]. Caplacizumab is a humanized anti-vWF nanobody that proved effective and safe in adults [3]. Data on caplacizumab use in children, and specifically for those < 12 years, are anecdotic. [4]
A 9-year boy presented at the Emergency Department with rapid onset abdominal pain and macrohematuria. No significant history or recent infection was reported. At clinical examination, he had a widespread petechial rash and hypertension (135/90 mmHg). Laboratory studies showed a normal white blood cell count, low platelets (4 × 103/µl) and hemoglobin (10.7 g/dL), 12% of schistocytes on blood smear, bilirubin 7 mg/dL, lactate dehydrogenase 2786 U/L, and undetectable haptoglobin. No additional evidence of central nervous system and kidney involvement (after resolution of hematuria) was detected. However, due to the severe hematologic involvement, the patient was transferred to the intensive care unit where he received intravenous steroids (prednisone equivalent dose of 2 mg/kg daily) and a 5-day course of PEX for presumed TTP, with good response in terms of platelet count (116 × 103/µl at day 6) (Fig. 1). After remaining stable for 2 days, the platelet count rapidly decreased to 14 × 103/µl, and PEX was started again. At the same time, the ADAMTS13 inhibitor was detected at 29 U/mL and ADAMTS13 activity suppressed (< 0.5%); therefore, a diagnosis of refractory aTTP was made, despite no trigger being identified. Considering the severity of the clinical course, off-label administration of caplacizumab was considered. After approval by local IRB and acquisition of parents’ consent, he received intravenous caplacizumab (at adult dose, 10 mg) followed by daily subcutaneous administrations at the same dosing for 30 days. Intravenous rituximab (375 mg/m2 weekly for four weeks) was also administered. A rapid and sustained response of platelet values was obtained (220 × 103/µl after 3 days, Fig. 1). Treatment with caplacizumab was well tolerated, except for a mild cutaneous reaction in the sites of subcutaneous administration. The patient was finally discharged after 52 days in good clinical condition with a platelet count of 376 × 103/µl and an ADAMTS13 activity of 69%. The patient later underwent weekly follow-up evaluations, always remaining in good clinical condition and presenting normal platelets and ADAMTS13 activity (Fig. 1).
Caplacizumab has proven effective in adults as add-on therapy for refractory aTTP [3]. Limited real-life data and sporadic case-reports describe its use in children, [4, 5] but indications for caplacizumab administration are limited to patients older than 12 years. Off-label administration of caplacizumab proved effective and safe for refractory aTTP in our patient, in combination with PEX and immunosuppressive drugs. Despite limited evidence being available on caplacizumab efficacy and safety in younger children, its use in refractory aTTP is a valuable option for patients not responding or relapsing early on conventional therapies.
References
Joly BS, Coppo P, Veyradier A (2017) Thrombotic thrombocytopenic purpura. Blood 129(21):2836–2846
Sayani FA, Abrams CS (2015) How I treat refractory thrombotic thrombocytopenic purpura. Blood 125:3860–3867
Scully M, Cataland SR, Peyvandi F, HERCULES Investigators et al (2019) Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 380(4):335–346
Dutt T, Shaw RJ, Stubbs M et al (2021) Real-world experience with caplacizumab in the management of acute TTP. Blood 137(13):1731–1740
Boudali J, Hallak B, Haeck M et al (2021) Immune-mediated thrombotic thrombocytopenic purpura in childhood treated by caplacizumab, about 3 cases. J Nephrol. https://doi.org/10.1007/s40620-021-00992-5
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics statement
The patient’s parents provided their consent to the publication of the manuscript.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Veltroni, M., Pegoraro, F., Scappini, B. et al. Off-label caplacizumab as add-on therapy in a 9-year-old boy with refractory aTTP. Ann Hematol 101, 1369–1371 (2022). https://doi.org/10.1007/s00277-021-04740-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-021-04740-4