Immune thrombocytopenia: Modern management, knowledge gaps, and future perspectives

Immune thrombocytopenia (ITP) is an autoimmune disorder with increased risk of bleeding due to a low number of platelets. The pathophysiology is complex and not fully understood, but platelet autoantibodies and/or CD8+ T-cells are responsible, via diverse mechanisms, for disrupting platelet production and enhancing platelet destruction. The symptomatology of ITP seems to be more complex than has traditionally been perceived as thrombocytopenia and bleeding as the disease often has impact on the health-related quality of life and daily functions. The management thus requires a holistic approach and patient involvement at every stage. Corticosteroids still represent the cornerstone of the first-line treatment. Treatment with corticosteroid should not exceed 6–8 weeks. Patients who fail to achieve remission with a short course of corticosteroids may require a second-line therapy. Most guidelines recommend starting with a thrombopoietin receptor agonist (TPO-RA), rituximab, or fostamatinib since these agents have been investigated in randomized trials and have well-characterized efficacy and safety profiles. Patient involvement to reach a shared decision regarding choice of therapy is essential as these treatments have different modes of administration and mechanisms of action. Less than 10% of adults ITP patients will fail to respond to and/or be intolerant of multiple second-line therapies and would thus require a third-line therapeutic option. Such patients may respond well to a combination of TPO-RA and an immunomodulatory agent. Splenectomy or a continuation with nontherapeutic agents that has different mechanism of action may be an alternative approach.