Home > Journals > La Rivista Italiana della Medicina di Laboratorio > Past Issues > La Rivista Italiana della Medicina di Laboratorio 2022 Marzo;18(1) > La Rivista Italiana della Medicina di Laboratorio 2022 Marzo;18(1):42-56



Publishing options
To subscribe
Recommend to your librarian


Publication history
Cite this article as



La Rivista Italiana della Medicina di Laboratorio 2022 Marzo;18(1):42-56

DOI: 10.23736/S1825-859X.22.00135-9


language: Italian

The icterus interference. Recommendations from the Extra-analytical Variability Working Group of Italian Society for Clinical Pathology and Laboratory Medicine (GdS VEA SIPMeL)

Margherita MORANDINI

Laboratorio Analisi, ASFO, Pordenone, Italia

“Jaundice” is defined as the yellow color of the skin, sclera and mucous membranes produced by a high concentration of bilirubin in the plasma. The interference of jaundice on laboratory tests is of a physical type (absorption of light between 400 and 520 nm) or of a chemical type (interference with the reagents of chemical or enzymatic methods). The presence of icteric interference in the plasma and its type (increase/decrease) depends on the method-instrument system. In general, it can be argued that negative interference is more frequent and important for creatinine, total proteins, total and HDL cholesterol, ammonia, folate and tobramycin; while a positive interference can involve phosphorus, magnesium, urea, FT3, testosterone, estradiol, fructosamine, acetaminophen, phenobarbital, theophylline, paracetamol. The debate on icteric interference on coagulation tests in photo-optic instruments does not yet have certain answers. The most recent data on the frequency of interference refer to 0.14% (0.06% on creatinine tests, 2.2% on total proteins, 3.9% on ammonia). The methods for detecting icteric interference are essentially three: visual, bilirubin measurement, automatic determination of the so-called “serum indices” (hemolysis, icterus, lipemia [HIL]). The latter are now the most widespread because they are more accurate and feasible on the large amount of biochemical tests. However, some issues exist for quality assurance and acceptability thresholds, as well as for non-harmonization. There are recommendations in the literature on the reporting of interfered plasma results: 1) for analytes with validated dilution method, it is recommended to dilute; 2) for analytes without validated dilution method or with clinically critical LoQ (limit of quantification) or where the dilution does not bring the I-index within the acceptable range, it is recommended to cancel the results; and 3) for analytes in which the manufacturer certifies that there is no interference up to the maximum bilirubin concentrations tested, the result should be accompanied by a comment: “highly icteric sample may influence the result. Interpretation within the clinical context is recommended.” Icteric interference in other biological liquids on biochemical tests, with the exception of triglycerides (underestimation), creatinine and proteins (overestimation), would appear to be less than 10%. In the cerebrospinal fluid, where xanthochromy can help in the diagnosis of previous subarachnoid hemorrhage, hyperbilirubinemia over 20 μmol/L determines a false positivity. As for urine, bilirubinuria and urobilinogen can alarm the false positives of ketones, leukocyte esterase and glucose and false negatives of pH and nitrites as well as of creatininuria. Icteric interference is not taken into due account by laboratories, as demonstrated by the investigation of the Working Group for the Preanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine. However, icteric interference challenges the accuracy of the analytical data and clinical interpretation. It is therefore recommended: 1) that laboratories are aware of the importance of this interference; 2) to provide for its detection through automated HIL methods; 3) to confirm the level of bilirubin effectively interfering on the individual tests, taking into account the specificity of the method-instrument system; 4) to treat the reporting of plasmatic tests affected by icterus as reported above; 5) to keep in mind that hyperbilirubinemia over 20 μmol/L determines false positivity in the cerebrospinal fluid for the diagnosis of previous subarachnoid hemorrhage; and 6) to use the dipstick information on bilirubinuria and urobilinogen for the verification of false positives of ketones, leukocyte esterase and glucose and false negatives of pH and nitrites as well as in the determination of creatininuria.

KEY WORDS: Jaundice; Guidelines; Bilirubin

top of page