Immunopathology of immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired bleeding disorder caused by complex immune dysregulation. ITP is a rare disorder with significant morbidity; patients experience bleeding symptoms and reduced quality of life. The pathogenesis of ITP can be observed at several levels: the mechanisms of thrombocytopenia, the loss of tolerance mechanisms, and underlying factors that drive its occurrence. Several mechanisms of platelet destruction and impaired platelet production are recognized as driving the disease. These mechanisms range from autoantibody-mediated platelet destruction, T cell-mediated cytotoxicity, complement-mediated destruction, and platelet desialylation leading to platelet clearance to thrombopoietin consumption. These alterations are driven by a loss of tolerance with impaired T regulatory and myeloid-derived suppressor cell surveillance. Several underlying factors may contribute to ITP pathogenesis by promoting this loss of tolerance, including genetic susceptibility, infections, the gut microbiome, and environmental influences. The numerous alterations described may be heterogeneous across patients with ITP, contributing to disease heterogeneity. Many patients require ITP treatment, which may target 1 or more of these mechanisms, with new therapies being developed to focus on specific pathways. Ultimately, identifying the main mechanism(s) driving ITP in a patient may allow individualized management. This review will highlight the major mechanisms of ITP immunopathology to deepen understanding of important pathways and therapies modulating these pathways.