Interference from heterophilic antibodies in Ca 19-9 testing: A case report

Immunoassays are widely used analytical techniques in clinical laboratories, which can be affected by interference, leading to erroneous test results. We present the case of a 38-year-old female patient with a thyroid nodule, who had been followed up with since 2012, was not taking medication, and had an implausible elevation of Ca 19-9, a commonly used biomarker for gastrointestinal malignancies. Interference arising from heterophilic antibodies in the differential diagnosis was considered. Measurements were repeated with the same patient sample on three different immunoassay analyzers. Ca 19-9 levels measured with the Abbott Architect i2000 device were high, while the results from the latter two instruments (COBAS e601 and ADVIA Centaur CP) were within normal limits. Serial dilutions of serum samples revealed non-linearity, suggesting assay interference. The heterophilic blocking tube procedure and polyethylene glycol precipitation resulted in a normal range of Ca 19-9 levels, confirming that a heterophile antibody interaction was the most likely cause of the abnormal results. In this paper, we present a narrative review of the current literature pertaining to false-positive Ca 19-9 caused by interference. We propose close collaboration between clinicians and the laboratory before exposing patients to the cost of additional testing when clinical non-compliance is suspected.