How we treat primary immune thrombocytopenia in adults

Abstract

Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple humoral and cellular immune abnormalities result in accelerated platelet destruction and suppressed platelet production in ITP. The diagnosis remains a clinical exclusion of other causes of thrombocytopenia. Treatment is not required except for patients with active bleeding, severe thrombocytopenia, or cases in need of invasive procedures. Corticosteroids, intravenous immunoglobulin, and anti-RhD immunoglobulin are the classical initial treatments for newly diagnosed ITP in adults, but these agents generally cannot induce a long-term response in most patients. Subsequent treatments for patients who fail the initial therapy include thrombopoietic agents, rituximab, fostamatinib, splenectomy, and several older immunosuppressive agents. Other potential therapeutic agents, such as inhibitors of Bruton's tyrosine kinase and neonatal Fc receptor, are currently under clinical evaluation. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.

Keywords: Diagnosis; Platelets; Primary immune thrombocytopenia; Treatment.

Fig. 1

Pathophysiology of ITP. Thrombocytopenia in ITP is the result of both increased platelet destruction and suppressed platelet production. Platelet autoantigens are abnormally recognized, processed, and presented by DCs, and then CD4⁺ T helper cells are activated toward a proinflammatory profile, which dictate the differentiation of B cells into autoantibody-secreting plasma cells. Autoantibodies not only mediate platelet phagocytosis by macrophages through Fcγ receptors (FcγRs) but also induce platelet desialylation and subsequent clearance through hepatocyte Ashwell–Morell receptors (AMRs). Splenic macrophages have increased expression of major histocompatibility complex (MHC)-II and CD86 and can also present autoantigens to Th cells. CD8⁺ cytotoxic T lymphocytes (CTLs) can directly lyse platelets or induce platelet apoptosis. Moreover, autoantibodies and CTLs interfere with megakaryocyte maturation and apoptosis, leading to decreased platelet production in ITP. AMR Ashwell–Morell receptor, FcγR Fcγ receptor, M1/M2 M1/M2 macrophage polarization, CDC complement-dependent cytotoxicity, AICD activation-induced cell death, DC dendritic cell, IDO indoleamine 2,3-dioxygenase, Tfh follicular T helper cell, Th T helper cell, Treg regulatory T cell, Breg regulatory B cell, Bmem memory B cell, MHC-II major histocompatibility complex-II, ↓ means decreased or downregulated, ↑ means increased or upregulated

Fig. 2

Overview of diagnosis and treatment of adult ITP. CBC complete blood count, Plt platelet count, IVIg intravenous immunoglobulin, HD-DXM high-dose dexamethasone, ANAs antinuclear antibodies, APLAs anti-phospholipid antibodies, TPO thrombopoietin, CT computerized tomography, MDS myelodysplastic syndrome, vWD von Willebrand disease