Pathophysiology of Autoimmune Thrombocytopenia: Current Insight with a Focus on Thrombopoiesis

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a significant reduction in the number of circulating platelets which is frequently associated with bleeding. The total count of platelets in the body is finely regulated by the balance between platelet production and destruction. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to alterations of both mechanisms. An abnormal proliferation of autoreactive T cells leading to the breakdown of immune tolerance to platelet antigens is suggested to be responsible for the up-regulated proliferation of autoantibody producing B cells. Consequently, the immune response induces enhanced T cell-mediated cytotoxicity and antibody-mediated platelet destruction through phagocytosis, complement activation and apoptosis. An additional contribution to the pathophysiology of ITP is given by alterations of thrombopoiesis caused by platelet-reactive autoantibodies or cytotoxic T cells leading to impaired megakaryocyte differentiation and platelet production. All these processes involved in ITP pathophysiology account for the complexity and heterogeneity in the clinical manifestation and therapy responsiveness of this disorder. For this reason, a better understanding of the different underlying mechanisms in ITP is necessary to develop more efficient therapeutic treatments in the future. In this review, we will provide an update on the pathophysiology of ITP with a particular focus on the impact of impaired thrombopoiesis.

Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management

“…Autoantibodies produced during ITP not only affect platelet survival but also platelet formation by megakaryocytes [32]. It has been shown that autoantibodies bind and hinder the megakaryocyte maturation, resulting in reduced platelet formation [33,34].…”

New Developments in the Pathophysiology and Management of Primary Immune Thrombocytopenia

“…Contraindications, potential adverse effects, and ineffectiveness of should be carefully evaluated. 20,49 IVIG include headache, aseptic meningitis, acute kidney injury, and hemolysis from passive transfer of anti-A and anti-B hemagglutinins in patients with non-O blood group. [54][55][56][57] Moreover, IVIG has been suggested to be associated with an increased risk of thrombosis.…”

Low T‐cell receptor excision circles (TREC) in children and adolescents with immune thrombocytopenia

“…Immune thrombocytopenia (ITP) is an autoimmune disease characterised by a low platelet number which is mediated by mechanisms comprised of autoantibodies, reactive CD8+ T lymphocytes and activated phagocytes which recognise either platelets or megakaryocytes 1,2 . ITP can be primary or secondary and its exact immune dysfunction remains unknown.…”