The Potassium Trap: Recognizing Pseudohyperkalemia in Hematologic Malignancies

Introduction: Pseudohyperkalemia and reverse pseudohyperkalemia, first described by Hartmann and Melinkoff in 1955, have become increasingly recognized, with a prevalence of up to 40% in patients with hematologic malignancies with leukocytosis (>50 × 109/L). Initially attributed to coagulation-induced potassium release in serum samples, other mechanisms have since been proposed including increased cell fragility, depletion of intracellular metabolites, and disruption of membrane integrity. We present a case of severe leukocytosis with pseudohyperkalemia and discuss the clinical implications. Case Description: A 74-year-old male lost to follow-up after a diagnosis of chronic lymphocytic leukemia (CLL) three years ago, currently being treated with one month of acalabrutinib, was admitted after an outpatient workup revealed worsening leukocytosis. Laboratory findings were significant for a white blood cell (WBC) count of 620,000/µL, hypokalemia (2.8 mmol/L), and a creatinine of 2.26 mg/dL (baseline ~1.2mg/dL). He was admitted for initiation of fludarabine, cyclophosphamide, and rituximab. On admission 24 hours later, his serum potassium level was markedly elevated at 9.8 mmol/L and 10 mmol/L on repeat testing. Other significant labs were WBC count 520,000/µL phosphorus 3.2mg/dL, calcium 7.7mg/dL, and uric acid 9.3 mg/dL. He was started on fluids and given a dose of rasburicase for tumor lysis syndrome (TLS) prevention; Nephrology was consulted for potential dialysis initiation. The patient remained asymptomatic, and EKG was negative for conduction abnormalities and arrhythmia. Calcium gluconate was administered and an arterial blood gas, ordered simultaneously, revealed a potassium level of 2.8 mmol/L, leading to discontinuation of further treatments. The patient continued chemotherapy with WBC down to 120,000/µL by day 3, with subsequent serum potassium levels remaining normal during his stay, confirmed with whole blood measurements. Discussion: Hyperkalemic emergencies often result in reflexive treatments with emphasis on rapid stabilization of membranes. The protocols ensure prompt treatment but could result in missing pseudohyperkalemia. It is imperative to confirm serum measurements with whole blood, especially in scenarios with discrepancies in clinical presentations and laboratory findings, to avoid complications like iatrogenic hypokalemia and unnecessary procedures.