Immune Thrombocytopenic Purpura (ITP): Expanding Options in Thrombopoietin Receptor Agonist Therapy

Immune Thrombocytopenic Purpura (ITP) is a rare autoimmune bleeding disorder in which the immune system mistakenly targets and destroys platelets—cells essential for blood clotting. The resulting thrombocytopenia (low platelet count) can cause spontaneous bruising, petechiae, and life-threatening hemorrhages. ITP can be primary or secondary to other conditions such as lupus, infections, or certain medications.

The disease can present acutely in children, often resolving spontaneously, but in adults, it tends to be chronic and relapsing. Prompt diagnosis and individualized treatment are key to preventing complications and improving long-term outcomes.

TPO Receptor Agonists: Doptelet, Nplate, Promacta

Thrombopoietin (TPO) receptor agonists have revolutionized the treatment of chronic ITP by stimulating platelet production in the bone marrow, offering an effective alternative to immunosuppressive therapies and splenectomy.

Promacta® (eltrombopag)

Promacta is an oral, once-daily TPO receptor agonist that stimulates megakaryocytes to increase platelet production. It is approved for both adult and pediatric patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Promacta requires routine monitoring of liver function and should be taken on an empty stomach due to potential interactions with food and supplements high in calcium or iron.

Nplate® (romiplostim)

Nplate is a subcutaneous injection administered weekly. It mimics endogenous thrombopoietin and binds to and activates the TPO receptor on bone marrow progenitor cells. Nplate has been shown to significantly increase platelet counts and reduce bleeding episodes in both adults and children with chronic ITP. Long-term use is generally safe, although patients require ongoing monitoring to avoid excessive platelet production.

Doptelet® (avatrombopag)

Doptelet is a newer oral TPO receptor agonist approved for adult patients with chronic ITP. Unlike Promacta, Doptelet can be taken with food, offering greater flexibility. In clinical trials, Doptelet effectively increased platelet counts with a favorable safety profile. It is also approved for use in thrombocytopenic patients with chronic liver disease undergoing procedures.

Diagnostic Considerations

ITP remains a diagnosis of exclusion. Key features include:

• ●  Isolated thrombocytopenia (platelet count <100,000/μL)
• ●  Normal red and white blood cell counts
• ●  No evidence of bone marrow failure or other causes of thrombocytopenia
•  

Additional work-up may include testing for HIV, hepatitis C, ANA, and Helicobacter pylori depending on clinical context. A bone marrow biopsy is typically reserved for atypical presentations or treatment-refractory cases.

Future Directions in ITP Treatment

As understanding of ITP's underlying immune dysregulation grows, treatment is shifting toward targeted therapies that restore immune tolerance and enhance platelet production. TPO receptor agonists like Promacta, Nplate, and Doptelet are now mainstays in chronic ITP management, offering durable responses with reduced bleeding risk.

Ongoing research is evaluating combination approaches (e.g., TPO-RA + rituximab), next- generation agents, and biomarkers to better predict response and tailor treatment duration. With these advancements, the prognosis for patients with chronic ITP continues to improve.