Artifactual Hyperbilirubinemia Due to Paraprotein Interference

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Abstract
Context.—Paraprotein interference in automated chemistry is uncommon. We describe 2 patients with paraproteinemia and elevated total bilirubin levels measured erroneously using the Roche total bilirubin assay. Objectives.—To explain the mechanism of this artifactual hyperbilirubinemia and to determine its frequency in patients with monoclonal or increased immunoglobulins. Materials and Methods.—The assay was performed manually using serum from 2 index patients and from control patients (without M proteins). Total bilirubin was also determined using another manufacturer's assay. A prospective study was then undertaken using serum from 100 consecutive patients with various monoclonal gammopathies and from 13 patients with polyclonal hypergammaglobulinemia and cryoglobulins. For all patients, serum immunoglobulin (Ig) G, IgA, IgM, total and direct bilirubin, creatinine, and a direct spectrophotometric assessment of icterus were measured. Results.—After the addition of assay reagents, a white precipitate formed in the reaction mixtures containing serum from the index patients, but not in other samples. This turbidity, rather than the expected color change to pink, increased the absorbance and falsely elevated the total bilirubin value. Serum from both index patients was anicteric, their direct bilirubin measurements were unaffected, and total bilirubin measured using an alternate assay was normal. Among the 113 patients studied, no additional spurious total bilirubin values were detected. Conclusion.—Paraprotein interference with the Roche automated total bilirubin assay is caused by precipitate formation. This interference is rare and probably idiosyncratic. Spurious hyperbilirubinemia from paraprotein interference may cause clinical confusion. If artifactual elevation of total bilirubin is suspected, the laboratory should examine the specimen for icterus (manually or by spectrophotometry) or measure total bilirubin using a different method.