Loh et al. report the clinical case of a patient with pseudohyperphosphatemia owing to paraprotein (monoclonal immunoglobulin) interference and remind us of the importance of correlating laboratory results with clinical findings and of encouraging communication between the laboratory and physicians.
Paraproteins are common interferents in routine chematology assays. More than 70 published reports have documented paraprotein interference with a variety of analytes, including calcium, direct and total bilirubin, creatinine, glucose, HDL and LDL cholesterol, iron, phosphate, sodium, urea, uric acid, coagulation tests, and blood cell counts (1). The importance of paraprotein interference should not be underestimated, given the prevalence of paraproteinemia (3.2% and 5.3% for persons ≥50 and ≥70 years of age, respectively)(2).
Paraproteins cause interference via several mechanisms. The most common is the formation of turbidity due to the precipitation of paraproteins during the test reaction. Test results can be falsely low or high. Paraprotein interference is underrecognized and underreported. Systematic studies of sera from patients with monoclonal gammopathies have reported that interference is far more frequent than can be inferred from case reports (3).
Given the prevalence of paraproteins and their interference with analyte measurements, more approaches are needed for reducing and detecting this interference. Manufacturers of diagnostic reagents can optimize reagents (e.g., detergents, ionic strength) to reduce interference and can flag interference by monitoring reaction kinetics and sample consistency. Laboratories can use software to identify samples that may have paraproteins or paraprotein interference. Examples of the use of test results and interference indices to identify such samples include (a) samples with a low albumin concentration and an increased total protein concentration, (b) samples with discordant interference indices and test results (e.g., an increased icteric index and normal total or direct bilirubin values), (c) samples with discordant test results (e.g., a direct bilirubin value greater than the total bilirubin value), and (d) samples with negative or improbable undetectable results (e.g., HDL cholesterol).
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2010 The American Association for Clinical Chemistry