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

Highlights• IgM-κ paraprotein caused marked platform-dependent interference in electrolyte and total calcium measurements • Total calcium differed by 71% between Hitachi and Beckman despite the same Arsenazo III reagent • Direct ion-selective electrode analysis excluded true hyponatremia and hypercalcemia • Platform-specific mixing dynamics determined the extent of paraprotein interference • Recognition of marked inter-platform discrepancies prompted targeted laboratory investigation, leading to identification of IgM paraprotein and diagnosis of occult Waldenström macroglobulinemia AbstractAccurate 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.