Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP)

Abstract

Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by low platelet counts. The pathogenesis of ITP remains unclear although both antibody-mediated and/or T cell-mediated platelet destruction are key processes. In addition, impairment of T cells, cytokine imbalances, and the contribution of the bone marrow niche have now been recognized to be important. Treatment strategies are aimed at the restoration of platelet counts compatible with adequate hemostasis rather than achieving physiological platelet counts. The first line treatments focus on the inhibition of autoantibody production and platelet degradation, whereas second-line treatments include immunosuppressive drugs, such as Rituximab, and splenectomy. Finally, third-line treatments aim to stimulate platelet production by megakaryocytes. This review discusses the pathophysiology of ITP and how the different treatment modalities affect the pathogenic mechanisms.

Oxidative Stress and Antioxidant Status in Immune Thrombocytopenia

“…Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to pathogenic antiplatelet autoantibodies, T cell-mediated platelet destruction, and impaired megakaryocyte function [1]. This disorder is classified as primary, also referred to as idiopathic thrombocytopenic purpura, or as secondary to an underlying disorder such as chronic infections, including Helicobacter pylori, or other autoimmune diseases including systemic lupus erythematosus (SLE) and antiphospholipid syndrome [2].…”

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

“…The pathogenesis of ITP remains incompletely understood, yet it appears to be highly multifactorial [1-3]. ITP involves isolated thrombocytopenia [4] as a result of anti-platelet antibody production by plasma cells that induce antibody-mediated platelet phagocytosis [5, 6], T-cell mediated platelet destruction [7], and/or impairment of megakaryocyte function [8-10].…”

“…Second line treatments include immunosuppressive agents such as anti-CD20 therapy with rituximab and splenectomy. Finally, third line treatments involve the stimulation of platelet production by megakaryocytes by Thrombopoietin-receptor agonists [1, 14]. …”

Fostamatinib for Persistent/Chronic Adult Immune Thrombocytopenia

“…The combined effects of platelet destruction and impaired platelet production often leads to severe thrombocytopenia with skin and mucosal bleeding and risk of serious intracranial and gastrointestinal bleeding complications [2][3][4]. Prevalence of ITP is estimated at 9.5 per 100,000 adults, and incidence rates have been reported at 3.3 adults per 100,000 years [5].…”