Pathophysiology and management of primary immune thrombocytopenia

Abstract

Primary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins, such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production, although autoantibody-independent mechanisms, such as T cell-mediated cytotoxicity, may also be involved in its pathogenesis. Recent advances in the localization of autoantigenic epitopes and the characterization of T cell functional abnormalities in ITP patients have improved our understanding of the pathophysiology of this disease. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized.

Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults

“…After dexamethasone treatment, 5 patients responded and 5 achieved CR. All patients achieved either R or CR by the time treatment with eltrombopag was complete (median 5 days, range [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The CR rate was 83.3%, whereas the R rate was 16.7%.…”

“…16 In this setting, eltrombopag increases Treg activity and therefore may play a role in altering the natural history of the disease, making the use of this drug in newly diagnosed ITP patients a compelling approach. 17 In spite of a limited follow-up, the median DOR (8.3 months) suggests that lasting remissions can be obtained without immunosuppression by adding a short eltrombopag course to dexamethasone.…”

Seasonal Association of Immune Thrombocytopenia in Adults

“…These autoantibodies cause both impaired thrombocyte production and thrombocyte destruction. However, Tcell mediated mechanisms independent from autoantibodies may also be involved (5). The presence of auto-reactive T cell clones against GPIIb/IIIa epitopes in patients with ITP were shown by Kuwana et al (19).…”

“…Cytotoxic T-lymphocytes are also involved in the pathophysiology of ITP. Therefore, ITP pathogenesis involves a complex network of systemic events including interactions between B and T-lymphocytes and inflammatory cytokines (5). ITP may be primary or in association with other disorders (secondary).…”

Tolerability and safety of the intravenous immunoglobulin octagam®10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials

“…Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by antibody-mediated destruction of platelets in the spleen and suppressed platelet production, which together lead to a reduced platelet count and an increased risk of bleeding [1][2][3]. ITP can occur in the absence of an underlying disease (primary ITP) or in association with other disorders (secondary ITP) [2,3].…”