Abstract
Paraprotein interference in routine chemistry assays is an under-recognised cause of a spurious result that does not match the
clinical picture, and bilirubin assays are among those susceptible to it through turbidity and direct spectral interference from a
high concentration of monoclonal immunoglobulin. We report a case of a 68-year-old man with known IgM monoclonal
gammopathy who presented with a total bilirubin of 187 μmol/L on routine chemistry despite normal liver function otherwise,
normal conjugated bilirubin by an alternative method, and no clinical or ultrasound evidence of hepatic or biliary disease. Serial
dilution of the sample produced a non-linear response inconsistent with a true bilirubin elevation, and repeat measurement by a
diazo method on an ultracentrifuged, paraprotein-depleted sample returned a bilirubin of 14 μmol/L, within the reference range.
We describe the interference mechanism, the clues that distinguished it from genuine hyperbilirubinaemia, and a practical
laboratory pathway for the discordant bilirubin result in a patient with known or suspected paraproteinaemia.
References
Nolan JP, Wong M, Boscato LM, et al. "Interference in immunoassay by paraprotein: a review". Clin Biochem Rev 27(2006): 195-202.
Bornhorst JA, Roberts RF, Roberts WL. "Assay-specific differences in lipemic interference in native and intralipid-supplemented samples". Clin Chem 50(2004): 2197-2201.
Doumas BT, Kwok-Cheung PP, Perry BW, et al. "Candidate reference method for determination of total bilirubin in serum: development and validation". Clin Chem 31(1985): 1779-1789.
Dimeski G. "Interference testing". Clin Biochem Rev 29 Suppl 1(2008): S43-S48.
Kroll MH, Elin RJ. "Interference with clinical laboratory analyses". Clin Chem 40(1994): 1996-2005.
Berth M, Bosmans E, Everaert J, et al. "Rheumatoid factor interference in the determination of cardiac troponin T". Clin Chem Lab Med 44(2006): 89-92.
Ismail AA. "A radical approach is needed to eliminate interference from endogenous antibodies in immunoassays". Clin Chem 51(2005): 25-26.
Sturgeon CM, Viljoen A. "Analytical error and interference in immunoassay: minimizing risk". Ann Clin Biochem 48(2011): 418-432.
Ward G, Simpson A, Boscato L, et al. "The investigation of interferences in immunoassay". Clin Biochem 50(2017): 1306-1311.
Rajkumar SV. "Updated diagnostic criteria and staging system for multiple myeloma". Am Soc Clin Oncol Educ Book 36(2016): e418-423.

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