Paraprotein interference in bilirubin assays: A case of multiple myeloma highlighting the reliability of dry chemistry

The presence of paraproteins in multiple myeloma can cause analytical interference, resulting in unusual and misleading biochemical outcomes. An uncommon but clinically relevant finding is the reporting of a negative direct bilirubin result on wet chemistry analyzers-an impossible outcome that strongly suggests analytical interference. A 60-year-old male presented with nonspecific symptoms. Liver function tests carried out on a wet chemistry analyzer indicated a total bilirubin of 0.39 mg/dL and a direct bilirubin of -7.67 mg/dL, which was not physiologically possible. There was no evidence of jaundice, and imaging appeared normal. Repeat testing with a dry chemistry analyzer indicated a total bilirubin of 1.0 mg/dL and a direct bilirubin of 0.1 mg/dL, aligning with the clinical picture. Further investigations confirmed the diagnosis of multiple myeloma with IgG-kappa monoclonal gammopathy. The discrepancy was attributed to paraprotein interference in the wet chemistry method. This case highlights a rare but important laboratory artifact-negative direct bilirubin due to paraprotein interference-and emphasizes the reliability of dry chemistry in such scenarios. Awareness of this interference is important for accurate diagnosis and avoiding unnecessary workup.