Unmasking Hidden Monoclonal Proteins: Leveraging the Lipemia Index

BACKGROUND: Early detection of monoclonal gammopathies is challenging, as they often remain undiagnosed until morbidity develops. Monoclonal proteins (M-proteins), particularly IgM, can interfere with the lipemia index (L-index) on chemistry analyzers, producing elevations in visually clear samples. The L-index may allow incidental detection of M-proteins, but its clinical value is uncertain. METHODS: A retrospective chart review was conducted on 78 patients with visually clear serum samples with Siemens Atellica CH930 L-index ≥2 to assess diagnoses and follow-up of previously known and newly identified M-proteins. L-index was measured on Atellica, Roche cobas Pro c503, and Ortho VITROS XT3400 in 40 additional samples from patients with an IgM M-protein to assess L-index sensitivity for M-proteins. A survey of laboratories examined current practices for managing such samples. RESULTS: Sixty-three of 78 patients with visually clear serum samples with a reproducible Atellica L-index ≥2 had an M-protein(s) (34 previously known; 29 newly identified). Among these, IgM kappa predominated (47/63; 66%), and 5/29 newly identified cases were diagnosed with Waldenström macroglobulinemia. In 40 additional samples with known IgM M-proteins, only one had an elevated Atellica L-index, and none were elevated on cobas or Vitros. Survey results showed wide variation in managing these samples. CONCLUSIONS: An elevated L-index on the Atellica in visually clear serum samples, though insensitive, is predictive of the presence of an M-protein. These findings were inconsistent across platforms, highlighting the lack of L-index standardization. Protocol development of an elevated L-index in clear samples will help recognize and manage incidental M-proteins.