IT AIN’T HYPERKALEMIA: ADULT-ONSET JAK2-POSITIVE POLYCYTHEMIA RUBRA VERA COMPLICATED BY THE DOUBLE WHAMMY OF CONCURRENT PSEUDOHYPERKALEMIA AND TRUE IATROGENIC DRUG-RELATED HYPONATREMIA

Pseudohyperkalemia is a well-known phenomenon that is sometimes misinterpreted as life threatening hyperkalemia and can lead to inappropriate and potentially life-threatening medical interventions. On the other hand, hyponatremia is the commonest dyselectrolytemia in clinical practice and the commonest causes of hyponatremia are often administered medications that are associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We report the simultaneous and concurrent existence of pseudohyperkalemia and true hyponatremia in a now 73-yo male who was diagnosed with adult-onset polycythemia rubra vera in early 2016, and was subsequently treated with Hydroxyurea for several years, then was switched to Anagrelide and Ruxolitinib in more recent years.  

Case Report.

A now 73-year-old male was diagnosed in early 2016 with JAK2-positive polycythemia vera on bone marrow biopsy following the incidental finding of elevated hemoglobin and platelet counts on routine blood testing. Except for a history of aquagenic pruritus reported for decades, he was otherwise asymptomatic. He never smoked and he did not have sleep apnea. For about 6 years from 2016 – 2022, he was treated with Hydroxyurea, an antimetabolite urea derivative, 500 – 1000 mg daily. In the summer of 2022, due to worsening persistent hyponatremia, Hydroxyurea was discontinued, and he was started on Anagrelide, an antiplatelet hematologic agent, 0.5 mg BID. In September 2022, he was also started on Ruxolitinib, an immunosuppressant kinase inhibitor and JAK inhibitor, initially 10 mg BID and over the past three years, Ruxolitinib was titrated upwards to a current dose of 15 mg BID. He gets monthly CBC and blood chemistry and had needed near monthly therapeutic phlebotomy treatments from March 2018 to April 2025. Over the same period, the patient has had elevated WBC (peak 48.21 K/cmm), RBC (peak 7.67 M/cmm), Hemoglobin (peak 16.5 g/dL), Hematocrit (peak 50.7%) and Platelet (peak 1,072 K/cmm), which have varied over the years with therapy at different times, initially on Hydroxyurea (2016 – 2022), switched to Anagrelide (2017 - Present), and started on Ruxolitinib (2022 – Present) (FIGURES). Nevertheless, he continued to exhibit significant hyperkalemia and hyponatremia through to 2025 (FIGURES). 

He was therefore referred to Nephrology in July 2025 for the evaluation of persistent albeit asymptomatic hyperkalemia and hyponatremia. As of July 2025, WBC was 17.08 K/cmm, Hemoglobin was 14.0 g/dL, Hematocrit was 42.0%, and platelet was 162 K/cmm on maintenance Anagrelide 1 mg daily, and Ruxolitinib 15 mg BID. At Nephrology evaluation, he was otherwise asymptomatic, blood pressure was normal, and examination was unremarkable. Kidney function remained normal with creatinine at 0.74 mg/dL. Lipid profile was normal with LDL 77 mg/dL, Triglycerides 50 mg/dL, HDL 80 mg/dL on Atorvastatin 10 mg daily. Liver function tests were normal. Serum potassium was 5.3 mmol/L and simultaneously measured plasma potassium was 4.8 mmol/L. Simultaneous serum and plasma sodium levels carried out by Nephrology in early August 2025 were exactly the same, at 131 mmol/L. He has since been discharged from the Nephrology Clinic and subsequent potassium testing would be only in plasma. It is acknowledged that no urine sodium nor urine osmolarity tests were completed earlier on. No thyroid function tests were completed but in early 2024, he had serum cortisol and cortisol co-stimulation tests carried out which returned normal, to rule out adrenal insufficiency causing hyperkalemia with hyponatremia.

An extensive review of the literature confirmed that indeed, both Hydroxyurea and Ruxolitinib can cause hyponatremia. It is therefore no surprise that our patient has continued to exhibit hyponatremia, albeit without symptoms. The patient has clear features of pseudohyperkalemia mostly related to the thrombocytosis from polycythemia rubra vera, and to a lesser extent due to the elevated hemoglobin and WBC indices. One important clue that should raise a red flag to the presence of pseudohyperkalemia is the report of elevated potassium levels in the absence of overt kidney dysfunction (FIGURE). Such concurrent observations must call for significant circumspection and scrutiny. We advised that subsequent potassium monitoring be carried out in plasma.

On another front, there are rare reports that suggest that sodium and potassium levels in conditions of hyperleukocytosis go in opposite directions, being driven by various hypothesized mechanisms that may involve cell breakdown and lysis with release of molecules including ATP, the impact on different cations especially sodium and potassium, ionic channels and transcellular shifts mostly of increased sodium influx into the lymphocytes. Interestingly in our patient, the serum potassium and serum levels over the past 5 years demonstrated tantalizingly mirror-image trajectories that would support the published theories (FIGURE ABOVE).