Refractory Severe Thrombocytopenia Associated with Intravenous Treprostinil Use: a Case Report

Background: Intravenous epoprostenol was the first drug approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial hypertension. Treprostinil, a tricyclic benzidene prostocycline analog of epoprostenol has been favored over epoprostenol due to its more advantageous mode of administration and similar efficacy. All prostocyclines are known to cause thrombocytopenia, but severe platelet reductions are rare below 100,000/μL.

Aim: We report the first case of severe thrombocytopenia associated with intravenous treprostinil with subsequent recovery of a normal platelet count following transition to epoprostenol.

Case Report: A 55 year-old Caucasian woman diagnosed with idiopathic pulmonary artery hypertension noted significant improvement in symptoms and exercise tolerance following initiation of intravenous treprostinil. However, she developed new onset severe thrombocytopenia with her platelet count falling to 51,000/μL (150,000–399,000/μL) and recurrent anterior epistaxis after receiving intravenous treprostinil for six months. She had no known hematologic disorders or history of recurrent bleeding and was not receiving any other new medications. There was no evidence of disseminated intravascular coagulation, hemolysis, coagulation factor deficiency, or splenic sequestration. Empiric treatment with corticosteroids was started for positive antiplatelet IgG direct antibody, but the platelet count further declined to 25,000/μL. The patient was subsequently transitioned from intravenous treprostinil to epoprostenol under the assumption that her severe thrombocytopenia was an idiosyncratic reaction rather than a class effect of prostocyclines. Her platelet count had returned to normal two weeks after the transition.

Conclusion: In practice, patients developing thrombocytopenia from epoprostenol are frequently switched to treprostinil hoping to attenuate the degree of thrombocytopenia. This case is the first report of severe thrombocytopenia associated with intravenous treprostinil, as well as its successful resolution following transition to another prostocycline analog, epoprostenol. Although the exact mechanism of thrombocytopenia is unknown, it raises a question if the cyclohexane ring on treprostinil compared to the lactone ring on epoprostenol can potentially lead to more severe thrombocytopenia. Although at this point, it is uncertain if severe thrombocytopenia is an idiosyncratic reaction to treprostinil, this report will hopefully draw attention to this potential adverse effect and identify the mechanism of this reaction.