Analytical interference by IgM paraprotein causing platform-dependent electrolyte discrepancies: a case-based...

Accurate measurement of serum electrolytes and calcium is essential for clinical management; however, monoclonal immunoglobulins, particularly IgM paraproteins, may cause misleading analytical interference. We report the case of an 85-year-old man admitted for low back pain whose serum sample showed marked inter-platform discordance in sodium and total calcium results. The Hitachi platform reported a "hypercalcemic crisis" (total calcium 4.95 mmol/L) and severe hyponatremia (125 mmol/L), whereas the Beckman Coulter AU platform showed only mildly elevated total calcium (2.89 mmol/L) and milder hyponatremia (133 mmol/L). This corresponded to a 71.3% difference in total calcium, despite both platforms using the Arsenazo III method. Direct ion-selective electrode measurements excluded true hyponatremia and hypercalcemia. Dilution studies, polyethylene glycol precipitation, reaction-curve inspection, and simulation experiments confirmed that IgM-related precipitation and optical scattering were the underlying mechanisms. Specifically, platform-specific mixing dynamics determined the magnitude of interference. Recognition of biochemical-clinical discordance and targeted method comparison prompted hematological evaluation and led to a diagnosis of Waldenström macroglobulinemia. This case highlights that unexplained analytical discrepancies may delay recognition of underlying disease if analytical interference is not appropriately investigated.