A clinical case study published in the November issue of Clinical Chemistry involving a patient with multiple myeloma ends with an unexpected finding. While increased production of monoclonal immunoglobulins is to be expected in patients who have this disease, “unusually high concentrations of serum immunoglobulins can result in multiple laboratory interferences, including the prozone effect, the volume displacement effect, and the precipitation interference,” wrote the two authors, Andrea Gilbert Jelinek, DO, and Lorin M. Bachman, PhD, DABCC, both in the department of pathology at Virginia Commonwealth University in Richmond.
As such, “laboratorians should remain attentive to potential sources of discrepant results in patients with high plasma protein concentrations and should take appropriate action to prevent the release of erroneous results,” the case study concluded.
In one of two accompanying commentaries, Jerry A. Katzmann, PhD, compared the case study to the story of Goldilocks and the three bears: “we appreciate when monoclonal immunoglobulin concentrations are not too high and not too low, but just right.”
Katzmann, associate professor of laboratory medicine and pathology at Mayo Clinic in Rochester, Minnesota, went on to explain, “The myeloma diagnosis in this case was known to the clinician, and laboratory results were consistent with myeloma-associated bone marrow suppression (hemoglobin, hematocrit, platelet count) and renal impairment (creatinine, urea nitrogen). The apparent absence of immunoglobulins might have suggested a nonsecretory or light chain myeloma except for the serum protein electrophoresis and dramatically increased serum total protein. Dilution and reanalysis of the serum yielded a quantitative IgG of 14 400 mg/dL, which was compatible with the serum M spike.”
Further describing the case study’s findings, “there are other idiosyncratic analytic problems caused by monoclonal immunoglobulins that are unrelated to concentration,” Katzmann wrote. Preanalytic and analytic cryoglobulin precipitates are the most common of these. “The unique nature of each monoclonal gammopathy warrants our attention to the entire case, and evaluation of such cases frequently benefits from open lines of communication with clinicians.”
In the second accompanying commentary, Jim D. Faix, MD, a clinical professor of pathology at the Stanford University School of Medicine in Stanford, California, wrote that the case study nicely documents three well-known effects these immunoglobulins can have on laboratory testing in vitro—but he thinks the report may only scratch the surface of the issue. “The prozone effect foiled accurate determination of the monoclonal IgG’s concentration, but monoclonal immunoglobulins exhibit other quirky behaviors that may similarly cause them to be under- or overestimated,” Faix explained. Also, the “pseudohyponatremia and falsely increased phosphate results described by the authors are well recognized in vitro problems,” his commentary stated.
What is less common are “inaccurate bilirubin results (caused by precipitation similar to that seen in the phosphate assay), abnormally high calcium results (with a free calcium concentration within the reference interval) owing to calcium binding by the immunoglobulin, and a variety of artifacts caused by serum with a high viscosity literally gumming up the works of an automated instrument,” Faix wrote, adding that the case study serves as a reminder for medical professionals to pay close attention to what he calls a “fascinating disease.”
Read the case study online.