A Review of Thrombopoietin Receptor Agonists and Subsequent Development of Thrombosis: Exploring a Hematologic Paradox

Thrombopoietin receptor agonists (TPO-RAs) are drugs that increase platelet production and reduce bleeding risk. Agents such as romiplostim, eltrombopag, avatrombopag, and lusutrombopag act in different ways to stimulate megakaryopoiesis. These agents are used in both adult and pediatric populations, primarily in chronic immune thrombocytopenia, severe aplastic anemia, and myelodysplastic syndrome, as well as pre-procedural in patients with chronic liver disease. This literature review summarizes the current TPO-RAs and aims to evaluate the risk of thrombus formation. Past studies have been inconsistent in significantly associating thrombotic events with higher platelet counts, medication doses, or drug mechanisms of action. The pathophysiology appears to be multifactorial, with some theories suggesting risk from increased thrombopoiesis with potential alterations in platelet activity or an already prothrombotic patient state due to underlying disease or individual predisposing factors. Risks such as prior thrombus formation, older age, history of splenectomy, antiphospholipid syndrome, prolonged TPO-RA exposure, and thrombotic risk associated with the underlying disease being treated are important to consider not only during treatment initiation but also during continued risk assessment.