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Thrombopoietin Receptor Agonists: Eltrombopag and Romiplostim for the Treatment of Chronic Immune Thrombocytopenia Purpura

Katie Atkinson
CJON 2019, 23(2), 212-216 DOI: 10.1188/19.CJON.212-216

The thrombopoietin receptor agonists, eltrombopag and romiplostim, are second-line agents used to treat chronic immune thrombocytopenia purpura (ITP) in adults and children. ITP is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, petechiae, wet purpura, or blood in the urine or stool. This article reviews ITP treatment for adult and pediatric patients, including the use of the oral agent eltrombopag and the injectible agent romiplostim, nursing considerations, and patient education.


  • ITP is primarily characterized by reduced platelet counts and classified based on disease duration.
  • Reduced platelet counts place patients at a higher risk for bleeding and related complications.
  • Eltrombopag or romiplostim can be effective maintenance therapy options for patients with chronic ITP requiring frequent treatments.

Immune thrombocytopenia purpura (ITP) is an uncommon autoimmune disorder where the body’s antibodies destroy platelet antigens and T cells associated with thrombopoietin, resulting in an increased risk for bleeding, bruising, and petechiae from reduced platelet counts (Rodeghiero et al., 2009). The estimated incidence of ITP is approximately 1 to 12 per 100,000 adults and 8 per 100,00 children annually (Terrell et al., 2012).


Diagnosis of ITP is based on the exclusion of other causes of thrombocytopenia because of side effects from drugs (e.g., heparin, penicillin, nonsteroidal anti-inflammatory drugs), secondary ITP (e.g., lupus), or infection (e.g., HIV, Heliobacter pylori [H. pylori], hepatitis C), as well as platelet counts of less than 100,000/ml (Rodeghiero et al., 2009). Although patients can present without excessive bleeding symptoms, most patients present with bruising, petechiae, epistaxis, wet purpura, fatigue, or prolonged or heavy menses. ITP diagnosis begins with a complete blood count evaluation and a peripheral blood smear, in addition to a thorough personal and family history evaluation and physical examination. If the test results are typical of ITP, no further evaluation is needed. Bone marrow examination may be considered in select patients who exhibit symptoms, such as fever or bone or joint pain, or in those who have a family history of low platelet counts or easy bruising; risk factors for HIV infection; skeletal or soft-tissue morphologic abnormalities; nonpetechial rash; lymphadenopathy; or an abnormal hemoglobin level, white blood cell count, or white cell morphology. These symptoms are not typical of ITP and require additional testing to rule out the possibility of other disorders (Neunert et al., 2011; Provan et al., 2010). ITP classification is based on disease duration from three months newly diagnosed to chronic disease being greater than 12 months. In addition, ITP can be classified as severe, indicated by significant bleeding requiring treatment, or refractory, demonstrated by a post-splenectomy relapse or high risk for bleeding, or it can be based on the response or complete response of platelet counts (Lambert & Gernsheimer, 2017; Rodeghiero et al., 2009). This article reviews first- and second-line ITP treatments, particularly use of the thrombopoietin receptor agonists (TPO-RAs), eltrombopag (Promacta®) and romiplostim (Nplate®), for adult and pediatric patients.

First-Line Treatments

The first-line treatment of ITP for low platelet counts or bleeding symptoms includes corticosteroids, such as prednisone or dexamethasone, and IV immunoglobulin (IVIG), or anti-D immunoglobulin (WinRh0) for nonsplenectomized patients. These treatment options provide a rapid but transient response in increasing platelet count and reducing bleeding symptoms if present. Steroids are preferred for first-line treatment and should be administered only on a short-term basis (Neunert et al., 2011).

Long-term steroid use can cause significant side effects, such as diabetes, hypertension, osteoporosis, or weight gain, among others (Guidry, George, Vesely, Kennison, & Terrell, 2009). For patients receiving IVIG, it is recommended that nurses monitor for infusion reactions. Patients receiving anti-D immunoglobulin are monitored for infusion reactions and hemolysis (Aptevo BioTherapeutics, 2016; Khan, Mydra, & Nevarez, 2017). Side effects of IVIG and anti-D immunoglobulin are similar and can include fever, chills, nausea, vomiting, and headache (Khan et al., 2017).

For patients with chronic ITP, approved first-line treatments are not ideal for repeated or prolonged administration. Complications associated with prolonged, or repeated, use of first-line ITP treatment therapies include acne, osteoporosis, diabetes, cataracts, weight gain, and infusion reactions (Cuker & Neunert, 2016; Harris, Tiganescu, Tubeuf, & Mackie, 2015).

Second-Line Treatments

To manage chronic ITP, treatment options should not only be effective but also safe, tolerable, and convenient for long-term use. Preferred second-line therapies for chronic ITP include splenectomy, TPO-RAs, and the anti-CD20 antibody rituximab. When splenectomy is contraindicated or not desired, a TPO-RA may be the best practice approach for treatment (Cuker, 2018; Raj, 2017).

TPO-RAs activate the thrombopoietin pathway, the main regulator of platelet production, to increase blood platelets. Two TPO-RAs, eltrombopag and romiplostim, bind to different parts of the thrombopoietin receptor and may activate it in different ways. Both are used clinically to treat patients with ITP. In addition, subcutaneous romiplostim, a peptide fusion protein, binds at the same site as endogenous thrombopoietin binding to increase platelet production. In 2018, romiplostim was approved for adult and pediatric patients with ITP as a second-line therapy (Amgen, 2018; Novartis Pharmaceuticals, 2018; Raj, 2017). Avatrombopag, which was also approved in 2018, is another non-peptide (small molecule) TPO-RA agent that can be administered orally as a once-daily therapy for the treatment of ITP in adults with chronic liver disease who are scheduled to undergo a procedure. However, additional monitoring and assessments of the clinical experiences of patients taking avatrombopag are required (Bussel, 2018). Additional agents that have been used for patients who have failed to respond to more conventional therapy generally include immunosuppresive agents, such as azathioprine, mycophenolate mofetil, cyclosporine, anti-CD52 monoclonal anitbodies, dapsone, and danazol (Neunert et al., 2011).

Eltrombopag Therapy

Eltrombopag, a non-peptide, small molecule TPO-RA, binds to the transmembrane region of the thrombopoietin receptor to stimulate blood platelet production. Similar to the clinical indications for romiplostim, eltrombopag is approved for treating adult and pediatric patients with chronic ITP who have had an insufficient response to first-line treatments, including, but not limited to, corticosteroids or immunoglobulins (Imbach & Crowther, 2011; Novartis Pharmaceuticals, 2018).

In adult and pediatric patients with chronic ITP, eltrombopag can improve blood platelet counts within weeks, reduce the risk of significant bleeding, and eliminate the need for concomitant ITP medications and rescue treatments, improving quality-of-life parameters (Khelif et al., 2016; Novartis Pharmaceuticals, 2018). Eltrombopag is an oral agent for chronic ITP that is administered once daily on an empty stomach at a starting dose of 50 mg for most adults and pediatric patients aged six years or older. Pediatric patients aged 1–5 years are administered a starting dose of 25 mg once daily (Novartis Pharmaceuticals, 2018). In addition, the recommended dosage is reduced for hepatic impairment and patients of Asian descent (Novartis Pharmaceuticals, 2018). The drug is titrated accordingly with the goal of maintaining platelet counts greater than or equal to 50 x 109/L but not exceeding 200 x 109/L. Although the overall aim is to minimize the risk of bleeding, the maximum dose cannot exceed 75 mg per day (Novartis Pharmaceuticals, 2018). Safe and effective use of eltrombopag requires regular evaluations of complete blood counts, as well as monitoring patients for adherence, dietary considerations, and side effects, including hepatotoxicity, thrombosis, and cataracts (Atkinson & Bussel, 2016; Novartis Pharmaceuticals, 2018).

Romiplostim Therapy

The TPO-RA romiplostim is indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to initial treatments, such as corticosteroids, immunoglobulins, or splenectomy. In 2018, it was approved for pediatric patients aged one year or older who have not responded to first-line treatment options or who have been experiencing symptoms of ITP for at least six months (Amgen, 2018).

Romiplostim is a subcutaneous injection that is administered once weekly at a starting dose of 1 mcg/kg. Similar to eltrombopag, romiplostim is titrated accordingly with the goal of maintaining platelet counts greater than or equal to 50 x 109/L. To reduce the risk for bleeding, the weekly dose of romiplostim can be adjusted by increments of 1 mcg/kg until the patient achieves a platelet count greater than 50 x 109/L. However, the weekly dose cannot exceed a maximum of 10 mcg/kg in adult or pediatric patients with chronic ITP (Amgen, 2018).

In settings of urgency, some practitioners may administer romiplostim at higher doses more rapidly than indicated in the drug package insert (e.g., 3 mcg/kg, 5 mcg/kg, 7 mcg/kg, and 10 mcg/kg) to increase platelet counts faster. Given the expense of romiplostim treatment, practitioners may round off to the nearest single-dose vial (e.g., 250 and 500 mcgs), where possible. In certain groups where oral intake is compromised, such as postoperative patients, patients who have an abnormal gastrointestinal tract, patients with liver disease, and small children who cannot go for long periods without dairy intake, romiplostim may be preferred over eltrombopag therapy. Additional instructions for eltrombopag and romiplostim administration are presented in Figure 1. 

Nursing Considerations

Oncology nursing considerations include knowledge of drug monitoring best practices, appropriate dose titrations, and meal time considerations, as well as an understanding of recommendations for discontinuation of eltrombopag and romiplostim (Novartis Pharmaceuticals, 2018). Safe and effective strategies for patient oral self-administration of eltrombopag involve ongoing monitoring, support, and follow-up with healthcare providers (Tokdemir & Kav, 2017). Until platelet counts are stabilized, complete blood counts are obtained biweekly, then monthly thereafter. The dosage regimen of eltrombopag and romiplostim may need to be modified based on platelet counts (see Table 1). 

Because patients with chronic ITP can become accustomed to low platelet counts, regular monitoring of patients ensures that platelet counts are stable and that necessary dosage adjustments can be made to maintain platelet stability. In addition, nurses can assess patients for potential side effects associated with TPO-RA administration, such as thrombocytopenia, thrombosis, and hepatic abnormalities, such as hepatotoxicity with eltrombopag (Novartis Pharmaceuticals, 2018). Continuous monitoring of patients, including weekly complete blood counts with platelets for four weeks or more, is warranted following discontinuation of eltrombopag and romiplostim (Atkinson & Bussel, 2016; Novartis Pharmaceuticals, 2018).

Because potential preexisting conditions and risk factors (e.g., cataracts related to repeated corticosteroid use) can affect the patient’s response to or the safety of eltrombopag therapy, it is helpful to obtain a baseline hepatitis panel to ensure that the best possible care is provided. Liver function tests, in particular serum aspartate aminotransferase, alanine aminotransferase, and bilirubin, should be measured before administering eltrombopag, every two weeks during the dose adjustment phase, and monthly following establishment of a stable dose. Additional tests are often recommended, including a baseline ocular examination before starting eltrombopag, as well as annual monitoring of patients for signs and symptoms of cataracts. In addition, the treating nurse practitioner may request additional tests or increase the frequency of routine monitoring in patients, particularly those with preexisting risk factors for bleeding (Atkinson & Bussel, 2016; Novartis Pharmaceuticals, 2018).

Patient Education

For patients with ITP receiving TPO-RAs, education includes an understanding of medication administration, dose adjustments, side effects, and, for eltrombopag therapy, dietary and supplement considerations. Patients are instructed to report any and all bleeding symptoms, particularly wet purpura and blood in the urine or stool, as well as any changes in the amount of bleeding or severity of symptoms. In addition, it is important to review the effects of blood thinning agents, such as aspirin, ibuprofen, and warfarin, on platelets with patients, as these can reduce the ability of blood to clot and can result in excessive bleeding (Atkinson & Bussel, 2016; Novartis Pharmaceuticals, 2018). To encourage adherence, nurse practitioners can educate patients and family caregivers on proper usage instructions.

For eltrombopag therapy, administering the dose with foods rich in divalent-ions (e.g., cereals, milk, ice cream, yogurt) or supplements (e.g., multivitamin, ferrous sulfate, calcium) can influence platelet counts and can reduce the efficacy of treatment. Therefore, meal timing requirements are a key component of patient education. Clinicians do not recommend eliminating certain food groups because this can have negative nutritional implications; instead, patients are instructed to either adjust the timing of ingesting these food groups or the timing of the dose. Because abrupt interruptions in dosing may cause a rapid decrease in platelet counts, any interruptions or discontinuation of eltrombopag therapy must be supervised by the patient’s healthcare provider. For this reason, expert opinion recommends tapering the dose. To avoid unintentional interruptions in treatment, nurse practitioners should remind patients to refill their prescriptions on time, to bring their medication with them when traveling, and to modify their travel diet as needed to ensure proper adherence. In clinical experience, eltrombopag therapy has been found to be well-tolerated, and reporting of adverse events that lead to discontinuation is infrequent (Atkinson & Bussel, 2016; Novartis Pharmaceuticals, 2018). 


TPO-RAs are effective treatment options for patients with chronic ITP based on convenience, tolerability, and ease of administration. They are recommended for patients with ITP who have not responded well to first-line treatment options and who require a treatment option that is convenient for long-term use. Although a detailed package insert is provided with eltrombopag and romiplostim medication, a discussion with the patient or family caregiver is important to confirm that the information is understood to maximize adherence to medication guidelines and dietary considerations, as well as to ensure that patients watch for possible signs and symptoms of negative side effects. Nurse practitioners are instrumental in educating patients on how to take medication properly, increasing the probability of stable platelet counts and, therefore, maximizing quality of life for patients.

About the Author(s)

Katie Atkinson, RN, BC-FNP, is a family nurse practitioner at Weill Cornell Medicine in New York, NY. The author takes full responsibility for this content. Atkinson has previously received support and provision of writing assistance from Novartis Pharmaceuticals. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Oncology Nursing Society. Atkinson can be reached at kaa9009@med.cornell.edu, with copy to CJONEditor@ons.org.



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