Pratheepan Puvanakumar^1,2

 

¹Department of Clinical Haematology, Royal Melbourne Hospital, Melbourne, Australia

²Department of Clinical Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia

 

Relapsed refractory immune thrombotic thrombocytopenic purpura (R/R iTTP) is a life-threatening primary thrombotic microangiopathy (TMA) associated with significantly increased morbidity and mortality.¹ The treatment paradigm in this difficult clinical scenario has been historically limited to increased volume/frequency of therapeutic plasma exchange (TPE), high dose corticosteroids, rituximab, splenectomy, cytotoxic therapies and, more recently, plasma cell directed therapies (e.g. bortezomib, daratumumab). 

 

Recent clinical advances such as the von-Willebrand factor (vWF) targeted nanobody (caplacizumab)² and recombinant form of a disintegrin and metalloprotease with thrombospondin type motif 13 (ADAMTS13)³ have been observed to show reduced rates of disease exacerbations and treatment refractoriness. However, neither of these medications are readily accessible in the current Australian therapeutic landscape for R/R iTTP.  

 

Furthermore, the other crucial therapeutic aspect of R/R iTTP is re-evaluation for previously unrecognised pathologies and/or management of concurrent co-morbidities (e.g. autoimmune disease, malignancies) or relevant physiological states (e.g. pregnancy). The following case studies will illustrate the clinical heterogeneity and spectral overlap of R/R iTTP, practical complexities of therapeutic management and recognition as immune-mediated phenomena associated with other pathological disorders and physiological states. 

 

1.     Farzana A. Sayani, Charles S. Abrams; How I treat refractory thrombotic thrombocytopenic purpura. Blood 2015; 125 (25): 3860–3867. doi: https://doi.org/10.1182/blood-2014-11-551580

2.     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., & HERCULES Investigators (2019). Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. The New England journal of medicine, 380(4), 335–346. https://doi.org/10.1056/NEJMoa1806311

3.     Scully M, Baptista J, Bhattacharya I, Cataland S, Coppo P, Cuccia L, Dutt T, Huang SH, Izquierdo CP, Mingot-Castellano ME, Parnes A. S305: Phase 2 randomized, placebo-controlled, double-blind, multicenter study of recombinant ADAMTS13 in patients with immune-mediated thrombotic thrombocytopenic purpura. HemaSphere. 2023 Aug 1;7(S3):e8651306.