Limitations and opportunities of whole blood bilirubin measurements by GEM premier 4000®

Abstract

BackgroundNeonatal hyperbilirubinemia has traditionally been screened by either total serum bilirubin or transcutaneous bilirubin. Whole blood bilirubin (TwB) by the GEM Premier 4000® blood gas analyzer (GEM) is a relatively new technology and it provides fast bilirubin results with a small sample volume and can measure co-oximetry and other analytes. Our clinical study was to evaluate the reliability of TwB measured by the GEM and identify analytical and clinical factors that may contribute to possible bias.Methods440 consecutive healthy newborn samples that had plasma bilirubin ordered for neonatal hyperbilirubinemia screening were included. TwB was first measured using the GEM, after which the remainder of the blood was spun and plasma neonatal bilirubin was measured using the VITROS 5600® (VITROS).Results62 samples (14%) were excluded from analysis due to failure in obtaining GEM results. Passing-Bablok regression suggested that the GEM results were negatively biased at low concentrations of bilirubin and positively biased at higher concentrations relative to the VITROS results (y = 1.43x-61.13). Bland-Altman plots showed an overall negative bias of the GEM bilirubin with a wide range of differences compared to VITROS. Both hemoglobin concentration and hemolysis affected the accuracy of the GEM results. Clinically, male infants had higher mean bilirubin levels, and infants delivered by caesarean section had lower hemoglobin levels. When comparing the number of results below the 40th percentile and above the 95th percentile cut-offs in the Bhutani nomogram which would trigger discharge or treatment, GEM bilirubin exhibited poor sensitivity and poor specificity in contrast to VITROS bilirubin.ConclusionsAn imperfect correlation was observed between whole blood bilirubin measured on the GEM4000® and plasma bilirubin on the VITROS 5600®. The contributors to the observed differences between the two instruments were specimen hemolysis and the accuracy of hemoglobin measurements, the latter of which affects the calculation of plasma-equivalent bilirubin. Additionally, the lack of standardization of total bilirubin calibration particularly in newborn specimens, may also account for some of the disagreement in results.

Neonatal hemoglobin affects the accuracy of whole blood bilirubin measurement on GEM Premier 4000 blood gas analyzers

“…Although Hb F and Hb A (majority of adult hemoglobin) have a slightly different light absorption spectra, it is important enough to be taken into account in the multi-component analysis of hemoglobin derivatives [ 18 , 19 ]. The inaccurate neonatal hemoglobin on the GEM observed in this study may also account for the bias of bilirubin measurements between blood gas analyzers and chemistry analyzers as seen in Wang’s study [ 8 ].…”

“…Additionally, the GEM underestimated bilirubin at low levels and overestimated bilirubin at high levels. It also identified that the GEM underestimated bilirubin at high hemoglobin levels [ 8 ].…”

“…Some validation studies using neonatal whole blood samples provided conflicting correlations between blood gas analyzers and chemistry analyzers [ [5] , [6] , [7] , [8] , [9] ], which confused physicians in interpreting whole blood bilirubin results for patient management. The common causes of bias are a lack of standardized plasma bilirubin reference methods [ 10 , 11 ] and the difference in methodologies between blood gas analyzers using multiple-wavelength photometry and chemistry analyzers using diazo based assay [ [5] , [6] , [7] , [8] , [9] ].…”

“…Some validation studies using neonatal whole blood samples provided conflicting correlations between blood gas analyzers and chemistry analyzers [ [5] , [6] , [7] , [8] , [9] ], which confused physicians in interpreting whole blood bilirubin results for patient management. The common causes of bias are a lack of standardized plasma bilirubin reference methods [ 10 , 11 ] and the difference in methodologies between blood gas analyzers using multiple-wavelength photometry and chemistry analyzers using diazo based assay [ [5] , [6] , [7] , [8] , [9] ]. Other factors contributing to the bias include neonatal hemoglobin interference [ 5 , 8 ], calculation of plasma equivalency on blood gas analyzers [ 8 , 9 ], increased conjugated bilirubin or delta bilirubin in samples [ 7 ], and variable blood albumin levels [ 12 ].…”

Analytical performance validation and clinical application of blood gas analyzer on the detection of neonatal bilirubin

“…Neonatal bilirubin has traditionally been measured by either total serum bilirubin or transcutaneous bilirubin (7). The application of a biochemical analyzer for venous blood bilirubin is currently considered a more reliable clinical method (8,9).…”