Immune thrombocytopenic purpura (ITP) is a clinical syndrome characterized by a decline in circulating platelets that manifests as a tendency to bleed (purpura or petechiae) in the absence of a systemic disease. ITP is an acquired autoimmune hemorrhagic disease with an incidence of approximately 3.3 per 100,000 adults and it can be acute or chronic. Primary ITP can be categorized as newly diagnosed (less than 3 months after diagnosis), persistent (3-12 months after diagnosis), and chronic (more than 12 months after diagnosis). Patients who do not respond to splenectomy, or who relapse, are considered to have refractory ITP.

ITP is generally caused either by a megakaryocyte maturation disorder that eventually manifests as insufficient platelet production or by antibody-mediated platelet destruction that exceeds the compensatory capacity of bone marrow. For ITP stemming from autoimmune etiology, an abnormal autoantibody, usually immunoglobulin G (IgG) with specificity for 1 or more platelet membrane glycoproteins, binds to circulating platelet membranes. Thrombocytopenia and purpura will develop if bone marrow megakaryocytes cannot increase production and maintain a normal number of circulating platelets.

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Treatment is typically aimed at immunomodulation and decreasing platelet destruction, and current therapeutic interventions include glucocorticoids, intravenous immunoglobulin, anti-D immunoglobulin, rituximab, and other immunosuppressive agents. These therapies can inhibit the production of antiplatelet antibodies and also decrease the number of immune cells. In addition, splenectomy can remove the site of platelet destruction mediated by macrophage FcgR, and in acute cases, it usually results in rapid, complete, and life-long clinical remission. However, in chronic ITP, the results are often less predictable, and splenectomy is generally not suitable for older adults because of the higher risk for complications and death.

The goal of treatment is to achieve a platelet level that will allow the patient to avoid major episodes of bleeding as opposed to attempting to bring platelet levels back to a normal range. But some patients are unable to reach even this threshold level, and many may relapse following first- and second-line treatment. Despite the availability of a wide range of treatments, many patients are unresponsive, resistant, or intolerant to therapy, due to the heterogeneity of the pathogenesis of ITP. In a paper published in Expert Review of Hematology, researchers highlighted the necessity of developing new treatments for this disorder and discussed current and emerging treatments that have been developed for ITP.

“Patients who are unresponsive to or intolerant of the standard treatments should be receiving individualized evaluation and management, and if possible, [they should] be enrolled into new clinical trials,” said author Renchi Yang, MD, professor and head of the Thrombosis and Hemostasis Center at the Chinese Academy of Medical Sciences and Peking Union Medical College in China.

“[Aside from] the thrombopoietin receptor agonists (TPO-RAs) and anti-CD20 antibodies, neonatal Fc receptor (FcRn) blockers or spleen tyrosine kinase (Syk) inhibitors may be of help for patients with refractory ITP,” Dr Yang added.

TPO and TPO-RAs

The primary interaction between TPO and TPO receptors promotes the viability and growth of megakaryocyte colony-forming cells as well as early megakaryocyte progenitors. Research has demonstrated that TPO concentrations are at normal or near normal levels in patients with ITP, which allows for the administration of supplemental exogenous TPO and TPO-RAs to improve platelet levels. The US Food and Drug Administration (FDA) has approved TPO-RA agents (ie, eltrombopag and romiplostim) for the treatment of adult chronic ITP.