Immune thrombocytopenia: a comprehensive review from pathophysiology to promising treatment modalities

ABSTRACT

Introduction: The present understanding of immune thrombocytopenia (ITP) is rapidly growing in tandem with the advent of new treatment modalities. This review article is a bird’s-eye view of ITP from pathogenesis to available therapeutic options, with extended focus on the novel agents.

Areas covered: ITP, an acquired autoimmune disorder characterized by isolated thrombocytopenia, can present as a primary disease in the absence of a known etiology of thrombocytopenia, or as a secondary entity associated with other autoimmune disorders, infections, or drug reactions. The pathophysiology of ITP is heterogeneous but generally includes both increased platelet destruction and decreased platelet production. Traditionally, ITP has been treated with immunosuppressive therapy, but the newer agents romiplostim and eltrombopag, which belong to the family of thrombopoietin (TPO) receptor agonists, have proved to be highly efficacious in treating the most refractory ITP cases with a favorable safety profile. Other therapies are also on the rise, including Syk inhibitors and anti-CD40L antibodies, among others.

Expert opinion: Although their mechanism of response durability is not yet fully understood, TPO receptor agonists have opened the door to a new era in the treatment of ITP, especially in light of their sustained response rates and minimal associated adverse events.

KEYWORDS:

• Eltrombopag
• immune
• immune thrombocytopenia (ITP)
• platelets
• romiplostim
• thrombopoietin
• thrombopoietin receptor agonist

Article highlights

• Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia.

• ITP can be either primary or secondary to other autoimmune diseases, infectious etiologies, or drug-related reactions.

• ITP is a disease of both increased platelet destruction and decreased platelet production.

• Antibodies against platelet surface antigens (glycoproteins [GPs] IIb/IIIa and Ib/IX) and decreased levels of circulating thrombopoietin (TPO) are the hallmark of the pathogenesis of ITP.

• The most common and feared complication of ITP is bleeding. Other symptoms include thrombosis and fatigue.

• First-line treatments of ITP include corticosteroids, intravenous immunoglobulin (IVIG), and anti-RhD.

• Second-line treatments of ITP include splenectomy, rituximab, danazol, and immunouppressive drugs such as azathioprine, cyclosporine, cyclophosphamide, and mycophenolate mofetil.

• Novel agents for ITP treatment include TPO receptor agonists, Syk inhibitors, and antibody therapies.

• TPO receptor agonists work by stimulating megakaryopoiesis.

• The TPO receptor agonists romiplostim and eltrombopag, which are FDA-approved for use in adult ITP, are highly effective at raising platelet counts to safe levels in chronic ITP, even in the most refractory of cases, with minimal side effects overall.

This box summarizes key points contained in the article.

Declaration of interest

A T Taher receives research funding and honoraria from Novartis Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.