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Neonatal jaundice is the characteristic yellowing of the skin and eyes in newborn children, caused by an accumulation of bilirubin following birth. Bilirubin is the naturally occurring break-down product from hemoglobin produced in all individuals. Bilirubin is a cytotoxic that must be cleared from the body. It is always produced in all individuals. It binds tightly to serum albumin, and is transported to the liver. There, bilirubin is conjugated to a sugar molecule, and excreted in the bile and stool.
In the fetus, this function is turned off. Instead, bilirubin crosses the placental barrier into the mother’s blood stream. The mother’s liver and other systems dispose of the child’s bilirubin. With birth, the newborn’s liver and other systems must “turn on”. This process can take 24 to 48 hours. During this period, it is common to see a significant rise from a normal bilirubin level, resulting in hyperbilirubinemia. In most children, the level of bilirubin is tolerable, and no injury occurs.
In some infants, the hyperbilirubinemia can reach dangerous levels. As the albumin binding sites for bilirubin are filled, free bilirubin levels rise in the blood. The unbound, unconjugated bilirubin can cross from the blood into tissue and the brain, causing cellular damage, leading to a range of neurological effects from reversible hearing loss, to palsy, to even death. These effects are sometimes collectively called kernicterus. When phototherapy is not adequate, a blood exchange transfusion may be necessary.
In the USA, measurement of the bilirubin is done by various assays that report the Total Serum Bilirubin (TSB). These assays cannot assay the unbound bilirubin. They are insensitive to the binding capacity of the albumin, which is a measure of the ability of the infant's blood to keep bilirubin from entering tissue and the brain. Presumably, the TSB-to-albumin ratio could provide insight to the binding capacity. However, this approach has proven unsatisfactory as it can not anticipate other factors that may influence bilirubin binding capacity . Transcutaneous reflectance assays of bilirubin are merely proxies of the TSB, and suffer additional short comings . Assays that directly measure binding capacity have not been successfully commercialized (like chromatography), or are not widely available (peroxidase assay). As a result, a grey zone exists where interpretation of the TSB assay is difficult. A child with exceptionally good binding capacity (and tolerable free bilirubin levels) may receive unnecessary treatment. Conversely, a child with poor binding capacity, and the same TSB, may not be recognized as at-risk, not receive the necessary treatment, and as a result, be injured. While the Subcommittee on Hyperbilirubinemia recommends that other risk factors be considered too , the uncertainty is not entirely resolved.
The bilirubin hematofluorometer provides a functional assay of the bilirubin binding capacity . The technology takes advantage of the fact that bilirubin bound to albumin will fluoresce. Free bilirubin does not fluoresce at significant levels . Therefore, a measurement of raw blood’s fluorescence in a drop of blood will provide a measure of the Bound Bilirubin level. A second drop of blood is doped with excess bilirubin. The available binding sites are then saturated, resulting in an increase in the fluorescence level. The higher level of fluorescence gives the Bilirubin Binding Capacity. The difference between the two measurements is the concentration of free binding sites available to hold additional bilirubin. This is the Reserve Binding Capacity. A low or absent Reserve Binding Capacity indicates a child at risk, possibly with dangerous levels of free bilirubin present. The free bilirubin level can be calculated from the ratio of Bound Bilirubin to the Reserve Binding Capacity. When this ratio approaches unity, 50% of the available binding sites are filled. A value for the serum free bilirubin level in nanomoles per liter, which we call the Saturation Index (SI), can be calculated from 10 x [Bound Bilirubin] / [Reserve Binding Capacity] .
At present, the bilirubin hematofluorometer has not received FDA approval. Guidelines for its use have not been accepted. The instrument is available for research purposes only.
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