Limits in the biology and the assay

Benign biology can shift a marker. AFP can rise with viral hepatitis, hepatitis flare, cirrhosis with active inflammation, and acute liver injury or regeneration. CA 19-9 can rise during biliary obstruction, cholangitis, choledocholithiasis, and pancreatitis, so interpretation is more reliable after biliary decompression and bilirubin normalization. A normal CA 19-9 also cannot exclude pancreatic cancer because Lewis-antigen-negative people may produce little or no measurable CA 19-9.

Serial interpretation needs method continuity. Results from different manufacturers are not numerically interchangeable, and a method change requires a new baseline, ideally with an interpretive comment. CLIA requires the laboratory to verify or establish a reportable range and reference intervals for its test system and make pertinent reference intervals available. The laboratory should use its verified interval, calibrator, reagent lot, and analyzer documentation rather than import an interval from another method.

Sandwich assays can be affected by high-dose hook effect, heterophile antibodies, biotin, and anti-analyte antibodies. Excess analyte can saturate capture and detection antibodies separately and yield a falsely low result in a two-site assay. Biotin bias direction is platform-specific, and thyroglobulin antibodies, abbreviated TgAb, most often make immunometric thyroglobulin falsely low or undetectable. Investigate a result that conflicts with the clinical pattern before calling it reassuring.