What Drug Is Used to Stimulate Platelets? An Overview of TPO-Receptor Agonists

In the United States, immune thrombocytopenia (ITP) affects approximately 9.5 to 21.4 per 100,000 adults annually, highlighting the need for effective treatments for low platelet counts. For patients at risk of bleeding, understanding what drug is used to stimulate platelets is critical for both physicians and patients. These advanced medications, known as thrombopoietin receptor agonists, have transformed treatment for many hematologic conditions.

Quick Summary

Thrombopoietin receptor agonists (TPO-RAs), including romiplostim and eltrombopag, are a class of medications used to stimulate the bone marrow to increase platelet production for conditions causing thrombocytopenia.

Key Points

• TPO-Receptor Agonists (TPO-RAs): This is the class of drugs that stimulate platelets, including romiplostim, eltrombopag, avatrombopag, and lusutrombopag.

• Mechanism of Action: TPO-RAs mimic the natural hormone thrombopoietin, binding to receptors on megakaryocytes in the bone marrow to increase platelet production.

• Routes of Administration: Romiplostim is an injection, while eltrombopag, avatrombopag, and lusutrombopag are taken orally.

• Indications: These drugs treat conditions like chronic immune thrombocytopenia (ITP), severe aplastic anemia, and thrombocytopenia related to chronic liver disease.

• Potential Side Effects: Risks include blood clots (thrombosis), bone marrow changes, and specific issues like liver enzyme elevation and cataracts associated with eltrombopag.

• Patient Considerations: The choice of medication depends on the specific diagnosis, patient tolerance, lifestyle factors, and potential drug interactions, especially with orally administered options.

Understanding Thrombopoietin and the Need for Stimulation

Thrombopoietin (TPO) is a natural hormone that regulates platelet production by binding to its receptor (c-Mpl) on bone marrow cells, signaling them to produce more platelets. In conditions like immune thrombocytopenia (ITP), where platelet counts are low, therapeutic intervention with platelet-stimulating drugs is often necessary because the body's natural increase in TPO production may not be sufficient.

The Role of TPO-Receptor Agonists (TPO-RAs)

Thrombopoietin receptor agonists (TPO-RAs) are the primary class of drugs used to stimulate platelet production. These drugs activate the TPO receptor on megakaryocytes, leading to increased platelet count. Modern TPO-RAs are designed to avoid the immunologic risks associated with earlier agents. Several TPO-RAs are available, including:

Romiplostim (Nplate)

Romiplostim is a "peptibody" administered weekly by subcutaneous injection. It is used for chronic ITP in adults and children and for acute radiation syndrome. Trials showed it can significantly increase platelet counts.

Eltrombopag (Promacta, Alvaiz)

Eltrombopag is an oral, small-molecule TPO-RA taken daily. It is approved for chronic ITP, severe aplastic anemia, and thrombocytopenia associated with chronic hepatitis C. Eltrombopag absorption is affected by polyvalent cations, requiring specific timing around food and supplements.

Avatrombopag (Doptelet)

Avatrombopag is an oral, small-molecule TPO-RA that can be taken with or without food and is not affected by polyvalent cations. It is used for chronic ITP and for thrombocytopenia in adults with chronic liver disease needing a procedure.

Lusutrombopag (Mulpleta)

Lusutrombopag is an oral, small-molecule TPO-RA primarily used for thrombocytopenia in adults with chronic liver disease requiring an invasive procedure. It can be taken with or without food.

Potential Side Effects and Monitoring

TPO-RAs can cause side effects. Common ones include headache, fatigue, and joint pain. More serious risks require monitoring:

• Thromboembolic events: Increased platelet counts can raise the risk of blood clots. This risk is higher in patients with chronic liver disease. Platelet counts are monitored to manage this risk.
• Bone marrow changes: TPO-RAs can lead to increased bone marrow reticulin, which can progress to fibrosis in rare cases. Monitoring includes blood tests and bone marrow biopsy if needed.
• Other agent-specific risks: Eltrombopag is linked to liver enzyme elevation and cataracts, requiring liver function tests and eye exams.

Comparison of TPO-Receptor Agonists

Feature	Romiplostim (Nplate)	Eltrombopag (Promacta/Alvaiz)	Avatrombopag (Doptelet)	Lusutrombopag (Mulpleta)
Route of Administration	Weekly Subcutaneous Injection	Oral, Daily	Oral, Daily	Oral, Daily (7-day course)
Mechanism of Action	Peptibody; Binds to the extracellular TPO-receptor site	Small molecule; Binds to the transmembrane TPO-receptor site	Small molecule; Binds to the transmembrane TPO-receptor site	Small molecule; Binds to the transmembrane TPO-receptor site
Dosing Schedule	Once weekly	Once daily	Once daily	Once daily for 7 days before a procedure
Dietary Restrictions	None	Avoid polyvalent cations (calcium, iron, etc.) 2-4 hours before/after dose	None	None
Key Indications	Chronic ITP, Acute Radiation Syndrome	Chronic ITP, Severe Aplastic Anemia, Chronic Hepatitis C-associated thrombocytopenia	Chronic ITP, Chronic liver disease-associated thrombocytopenia pre-procedure	Chronic liver disease-associated thrombocytopenia pre-procedure
Monitoring	Platelet counts	Platelet counts, Liver function tests, Ocular exams	Platelet counts	Platelet counts

Conclusion

TPO-RAs have significantly improved the treatment of thrombocytopenia by stimulating platelet production. These agents have enhanced the management of low platelet counts and their associated risks. For more information, refer to resources like {Link: NIH https://www.nhlbi.nih.gov/health/platelet-disorders/treatment}.

Frequently Asked Questions

What is the main drug class used to stimulate platelets?

The main drug class used to stimulate platelets is known as thrombopoietin receptor agonists (TPO-RAs). This class includes medications like romiplostim, eltrombopag, avatrombopag, and lusutrombopag.

How do TPO-RAs like romiplostim and eltrombopag work?

TPO-RAs work by binding to and activating the thrombopoietin (TPO) receptor on megakaryocytes in the bone marrow. This activation signals the megakaryocytes to proliferate and mature, leading to increased production of new platelets.

Is there a difference between oral and injectable platelet-stimulating drugs?

Yes, romiplostim (Nplate) is an injectable TPO-RA, typically given once weekly, while eltrombopag, avatrombopag, and lusutrombopag are oral medications taken as tablets. The choice between them can depend on patient preference and specific medical conditions.

Which drug is used to stimulate platelets before a surgical procedure?

Avatrombopag (Doptelet) and lusutrombopag (Mulpleta) are approved for treating thrombocytopenia in adults with chronic liver disease who are scheduled for an invasive procedure. They are given as a short course before and around the time of the procedure.

What are the common side effects of platelet-stimulating medications?

Common side effects can include headache, fatigue, joint or muscle pain, nausea, and dizziness. Eltrombopag can also cause increased liver enzyme levels and cataracts.

What are the serious risks associated with TPO-RAs?

Serious risks include an increased chance of developing blood clots (thrombosis) and potential bone marrow changes, such as increased reticulin fibrosis. These risks require close monitoring by a healthcare provider.

How does eltrombopag interact with food?

Eltrombopag is affected by foods and supplements containing polyvalent cations, such as calcium and iron. It should be taken on an empty stomach, at least four hours after and two hours before consuming these products, to ensure proper absorption.