Avatrombopag-induced lactic acidosis in a patient with severe thrombocytopenia

A woman in her 60s was admitted for refractory thrombocytopenia, initially presumed to be from immune thrombocytopenia (ITP). She was treated with the thrombopoietin receptor agonist (TPO-RA) avatrombopag, as well as prophylactic ciprofloxacin and fluconazole for neutropenia. She developed an anion gap metabolic acidosis with a significantly elevated lactate level peaking at 7.5 mmol/L. Other causes of lactic acidosis including hypovolaemia, sepsis, ischaemia and diabetic ketoacidosis were ruled out. Avatrombopag was discontinued, with quick resolution of the lactic acidosis. Fluconazole and ciprofloxacin were found to inhibit the metabolism of avatrombopag and were also discontinued. Worsening thrombocytopenia prompted a rechallenge with increased dose avatrombopag and severe lactic acidosis again developed, with subsequent quick resolution after drug discontinuation. We conclude that a dose-dependent lactic acidosis occurred with avatrombopag in this case. While other TPO-RAs including eltrombopag have been associated with lactic acidosis, to our knowledge, this is the first report of avatrombopag-induced lactic acidosis.