S5527 Common Prescription, Uncommon Reaction: Hematologic Toxicity Associated With Proton Pump Inhibitor Use

Introduction: Proton pump inhibitors (PPIs) are a widely prescribed class of medications used to treat a range of gastrointestinal conditions, including gastroesophageal reflux disease (GERD), dyspepsia, peptic ulcer disease, and Helicobacter pylori infection. While PPIs are typically well tolerated and have a favorable safety profile, rare hematologic complications such as neutropenia and agranulocytosis have been reported. In this case, we present a patient who developed leukopenia and thrombocytopenia shortly after recent initiation of a proton pump inhibitor. Case Description/Methods: A 29-year-old man with a medical history of migraines presented to the hospital with complaints of fever and chills. Notably, he had been hospitalized 2 weeks earlier for chest pain, during which time his complete blood count (CBC) was within normal limits: white blood cell count (WBC) of 5.6 × 103/uL, red blood cell count of 5.4 × 106/uL, hemoglobin of 14.3 g/dL, and platelets of 265 × 103/uL. Troponins and electrocardiogram were unremarkable at the time. After further workup his symptoms were attributed to musculoskeletal pain and gastroesophageal reflux disease. He was discharged on pantoprazole 40 milligrams (mg) daily. On his current admission, laboratory results revealed leukopenia with a WBC of 1.4 × 103/uL and thrombocytopenia with platelets of 121 × 103/uL. After thorough workup, no infectious or autoimmune cause was identified. Given the recent initiation, pantoprazole was suspected to be the reason for the observed leukopenia. Pantoprazole was subsequently discontinued, and follow-up labs demonstrated resolution of leukopenia, supporting the diagnosis of PPI-induced leukopenia. Discussion: Although uncommon, leukopenia and thrombocytopenia are recognized as adverse effects associated with proton pump inhibitor use. Although pathophysiology is not fully understood, suspected mechanisms include the production of drug-induced antibodies, or direct toxicity toward hematopoietic cells. This emphasizes the importance of maintaining a high index of suspicion in hematologic complications in patients presenting with unexplained cytopenias after initiation of PPI therapy. Early identification and discontinuation of the medication can assist with recovery.