The US FDA has approved the thrombopoietin receptor agonist avatrombopag (Doptelet®, AkaRx Inc) for the prevention of bleeding events in patients with chronic liver disease and thrombocytopenia undergoing a planned medical or dental procedure.
- Thrombopoietin receptor agonist, stimulates platelet production
- Decreases serious bleed risk 2-3 fold in patients w/ severe thrombocytopenia (<50*109/L) and chronic liver disease undergoing invasive procedures for up to 7 days after procedure
- Most common adverse events: fever, abdominal pain, fatigue, edema, nausea
- Current treatment: pre-procedural platelet transfusion
- May increase risk of thromboembolism in some patients
- 2 Phase III clinical trials (ADAPT-1, ADAPT-2)
- 435 patients, 40 or 60 mg PO QD x5, procedure 5-8d after last dose
- >50% of patients had viral etiologies for liver disease
- Tx and placebo arms similar rates of adverse events
What is thrombocytopenia?
Thrombocytopenia occurs when a patient’s platelet count falls below 150*109/L. Platelets play an important role in the formation of blood clots, and their depletion increases the risk of uncontrolled bleeding. Chronic liver disease, most often a consequence of viral hepatitis or alcohol use disorder, is among the most common causes of thrombocytopenia. As many as 84% of patients with liver cirrhosis may develop thrombocytopenia during the course of the disease.
What is a thrombopoietin receptor agonist?
Thrombopoietin agonists increase the rate of platelet production by activating thrombopoietin receptors in the bone marrow. This leads to increased differentation of megakaryocytes – platelet precursors – and increases circulating platelet counts. The most widely used thrombopoietin agonist is eltrombopag, which is FDA-approved for the 2nd-line treatment of of chronic idiopathic thrombocytopenia, severe hepatitis C infection, and in refractory aplastic anemia.