Refractory immune thrombocytopenia in adults: Towards a new definition

Abstract

SummaryImmune thrombocytopenia (ITP) is an autoimmune haematological disorder characterized by immune‐mediated thrombocytopenia and a variable risk of bleeding. Despite the availability of multiple treatment options, some patients are considered refractory since they do not achieve a platelet count response to multiple treatments and are at risk of bleeding. The term ‘refractory’ has been used to identify this patient group; however, with the advent of multiple lines of treatment, its meaning has become ambiguous. To address this issue, we reviewed previous definitions of refractory ITP, solicited the views of ITP experts and collected data from registries to inform a definition. Twenty ITP experts who attended the 7th Expert Meeting of the Intercontinental Cooperative ITP Study Group in September 2022 answered a web‐based survey: 95% felt that there was a need for a new definition of refractory ITP for clinical and research purposes. The use of the term refractory, accompanied by a clear indication of the type and timing of failed treatments, was supported by 85% of respondents. Preliminary data on the frequency of refractory patients from the McMaster and Norwegian ITP Registries demonstrated that the proportion of adult ITP patients who had failed first‐line therapy, rituximab, thrombopoietin receptor agonists, any immune suppressant medication and splenectomy ranged from 0.4% to 3.8%. We propose a definition of refractory ITP that could be evaluated in future studies.

Treatment of Immune Thrombocytopenia: Contextualization from a Historical Perspective

“…They reported that the threshold value to identify a “low” platelet count is variable, depending on the patient’s age, comorbidities, and concomitant therapies (e.g., antiplatelet or anticoagulant agents) [ 116 ]. In 2023, Arnold DM et al proposed the following definition of refractory ITP for consideration and future evaluation: persistence of severe thrombocytopenia (platelets < 20 × 10 9 /L) and bleeding in a patient with ITP who has received rituximab, two different TPO-RAs, and at least one immunosuppressant medication and who does not respond or only briefly responds to high-dose corticosteroids or high-dose IVIGs (less than 7 days) [ 117 ].…”

“…Although it was traditionally considered that 20% of patients do not achieve an adequate platelet count after splenectomy or after initial and subsequent medical treatment [ 13 ], nowadays, this percentage is probably much lower and difficult to estimate due to the lack of current consensus for the definition of refractoriness. Preliminary data from the McMaster and Norwegian ITP registries demonstrate that the proportion of adult ITP patients who have received first-line therapy, rituximab, at least one TPO-RA, and splenectomy ranges from 3.1% to 4.7% [ 117 ].…”