Why do hemolysis interference studies produce different results? A proposal for standardized experimental design and...

Hemolysis is a major preanalytical source of laboratory interference, but methods used to experimentally generate hemolyzed specimens are poorly standardized.

Different lysis procedures, blood sources, cellular compositions, hemolysate volumes, control designs, and time-to-analysis can influence results independently of free hemoglobin concentration. The amount and composition of intracellular material released may also vary with erythrocyte, leukocyte, and platelet characteristics. Therefore, identical hemolysis indices do not necessarily represent equivalent experimental interferents.

Hemolysis interference studies should clearly distinguish the interferent, its method of generation, and its measurement. Detailed reporting of specimen preparation and experimental conditions is essential for reproducibility and comparison between studies.

Harmonized hemolysate preparation and reporting, together with assessment at clinically relevant measurand concentrations and, when appropriate, multiple time points, would improve the reliability of hemolysis thresholds and laboratory decision-making.