patient care perspectives

The Changing Clinical Treatment Landscape in Chronic Immune Thrombocytopenia

by Terry B. Gernsheimer, MD


Over the past decade, the understanding of immune thrombocytopenia (ITP) has expanded greatly through clinical studies and literature updates, which has led to substantial treatment advances in the management of the disease. Novel therapies have provided safe and effective alternatives to splenectomy, with the approval of thrombopoietin receptor agonists (TPO-RAs) eltrombopag and romiplostim greatly changing the treatment landscape. TPO-RAs work by activating thrombopoietin (TPO) receptors on megakaryocytes and inducing platelet production via the Janus kinase 2/signal transducer and activator of transcription 5 pathways. Romiplostim is an immunoglobulin G heavy chain with 4 TPO agonist peptides inserted, and eltrombopag is an oral small molecule. These 2 agents activate the TPO receptor by different mechanisms to increase megakaryocyte growth and platelet production. They have different routes of administration, with romiplostim being given by subcutaneous injection and eltrombopag being an oral medication. In clinical trials, TPO-RAs significantly increased platelet response rates, reduced the incidence of bleeding events, and reduced the use of rescue medications in patients with chronic ITP.

Expert Commentary

Terry B. Gernsheimer, MD

Director of the University of Washington
Medical Transfusion Service
Professor of Medicine, Division of Hematology
University of Washington
Seattle, WA

“With increased knowledge of the pathophysiology, we now recognize why TPO-RAs may be helpful in patients with chronic ITP.”

Terry B. Gernsheimer, MD

We have previously misunderstood the pathophysiology of ITP—that it is a production as well as a destructive defect. With increased knowledge of the pathophysiology, we now recognize why TPO-RAs may be helpful in patients with chronic ITP. TPO levels are not increased in patients with ITP, as we had expected. In fact, in some patients, they are actually lower than normal. TPO-RAs have moved up on the list of treatments and now are one of the initial second-line management options. Bleeding is not predictable unless platelet counts are very, very low, but other risk factors must be taken into account, including older age, uncontrolled hypertension, work, and activities. The TPO-RAs are probably equal in efficacy and safety, so ease of access, dietary restrictions, and insurance may be considerations. The TPO-RAs appear to be safe and effective for long-term use. Therefore, the use of anti-CD20 therapy and splenectomy may be less-desirable options because they are less effective and more immunosuppressive. This is especially true early in the course of the disease, when spontaneous remissions may occur but a patient requires secondary therapy to discontinue steroids.


Khan AM, Mydra H, Nevarez A. Clinical practice updates in the management of immune thrombocytopenia. P T. 2017;42(12):756-763.

Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98(1):10-23.

Wang L, Gao Z, Chen XP, et al. Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: a systematic review and meta-analysis. Sci Rep. 2016;6:39003.

Zhang J, Liang Y, Ai Y, et al. Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis. Sci Rep. 2018;8(1):576.

Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in iImmune thrombocytopenia (ITP). J Clin Med. 2017;6(2):E16.

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