Relationship of Unbound Bilirubin Concentration to Reserve Albumin-Binding Concentration for Bilirubin in Human Neonatal Plasma

Neonatology ◽  
1984 ◽  
Vol 46 (3) ◽  
pp. 105-109
Author(s):  
Warren B. Karp ◽  
Alex F. Robertson ◽  
Harry C. Davis
Keyword(s):  
Albumin Binding ◽  
Bilirubin Concentration ◽  
Unbound Bilirubin ◽  
Relationship Of ◽  
Reserve Albumin

Criteria for Exchange Transfusion in Jaundiced Newborns

PEDIATRICS ◽  
1994 ◽  
Vol 93 (3) ◽  
pp. 488-494
Author(s):  
Charles E. Ahlfors
Keyword(s):  
Serum Albumin ◽  
Exchange Transfusion ◽  
Full Term ◽  
Albumin Binding ◽  
Albumin Concentration ◽  
Bilirubin Concentration ◽  
Albumin Ratio ◽  
Unbound Bilirubin ◽  
Frequency Curves ◽  
Normally Distributed

Objective. A widely published set of exchange transfusion criteria lowers critical bilirubin concentrations when the serum albumin falls to <2.5 g/dL. Although acknowledging the role of bilirubin-albumin binding in bilirubin neurotoxidty, this approach may inadvertently produce two critical bilirubin concentrations. This study investigates using the bilirubin/albumin ratio instead of the single albumin concentration to eliminate this potential ambiguity in the criteria. Design and participants. The bilirubin/albumin ratio was defined as a reliable indicator of bilirubin-albumin binding if the frequency curves of specific unbound bilirubin concentrations are normally distributed functions of the ratio. Therefore the bilirubin/albumin ratios at which the unbound bilirubin reached 10, 15, and 20 nmol/L were determined by the peroxidase method in 35 well full-term, 10 ill full-term, and 19 ill preterm neonates. The frequency curves for each unbound bilirubin concentration plotted against the bilirubin/albumin ratio were tested for normality. Results. The frequency of each unbound bilirubin concentration was a normally distributed function of the bilirubin/albumin ratio. Furthermore, the mean ratio at which each unbound bilirubin occurred did not differ significantly among the groups of neonates. Conclusion. The bilirubin/albumin ratio is a simple, nonambiguous way of incorporating the serum albumin concentration into exchange transfusion criteria.

Effect of serum dilution on apparent unbound bilirubin concentration as measured by the peroxidase method.

1981 ◽  
Vol 27 (5) ◽  
pp. 692-696 ◽  
Author(s):  
C E Ahlfors
Keyword(s):  
Dissociation Rate ◽  
Albumin Binding ◽  
Bilirubin Concentration ◽  
Serum Dilution ◽  
Apparent Concentration ◽  
Unbound Bilirubin ◽  
Bilirubin Binding ◽  
Accuracy Of Results ◽  
Bilirubin Toxicity ◽  
Rate Limiting

Abstract I studied the effects of serum dilution and oxidation of albumin-bound bilirubin on the accuracy of results by the peroxidase method for assessing bilirubin-albumin binding. The apparent concentration of unbound bilirubin decreases with dilution of bilirubin-enriched serum or defatted-albumin solutions, the effect being more marked with serum. The decrease in apparent unbound bilirubin does not appear to be due to slow oxidation of albumin-bound bilirubin. Instead, the bilirubin-albumin complex has a much lower apparent dissociation rate constant (K-1) in serum (0.0033 [SD 0.0002] s-1) than in solutions of defatted-albumin (0.017 [SD 0.006] s-1), causing the dissociation of the complex to be rate-limiting when serum is analyzed at the currently recommended 40-fold dilution and peroxidase concentration (0.11 mu mol/L). In addition, dilution appears to enhance bilirubin binding by serum but not by defatted-albumin solutions. Decreasing the serum dilution and peroxidase concentration may significantly improve the accuracy of the peroxidase test. The actual correlation between clinical bilirubin toxicity and specific unbound bilirubin concentrations, however, remains to be determined.

Transcutaneous Bilirubinometry: A New Light on an Old Subject

PEDIATRICS ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 124-125 ◽  
Author(s):  
Thomas Hegyi
Keyword(s):  
Central Nervous System ◽  
Skin Color ◽  
Serum Bilirubin ◽  
Cellular Injury ◽  
Bilirubin Concentration ◽  
Specific Serum ◽  
Relationship Of ◽  
The Relationship ◽  
Transcutaneous Bilirubinometry

The role of bilirubin as a cause of central nervous system morbidity in the newborn infant has been well recognized for several decades. The specific serum concentration that leads to cellular injury, as well as the precise mechanism of damage, are as yet unclear but general principles of therapy have been established. Early detection of hyperbilirubinemia is based on the clinical assessment of dermal icterus followed by appropriate serum tests to determine the degree of serum bilirubin elevation. The relationship of dermal icterus and serum bilirubin concentration has intrigued clinicians for more than a century.1 In an attempt to utilize skin color as an index of hyperbilirubinemia many techniques have been investigated.

scholarly journals Possible Ibuprofen-Induced Kernicterus in a Near-Term Infant with Moderate Hyperbilirubinemia.

2006 ◽  
Vol 11 (4) ◽  
pp. 245-250
Author(s):  
Peter Gal ◽  
J Laurence Ransom ◽  
Sherri A Davis
Keyword(s):  
Neonatal Intensive Care ◽  
Serum Bilirubin ◽  
Primary Pulmonary Hypertension ◽  
Term Infant ◽  
Auditory Neuropathy ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Albumin Binding ◽  
Unbound Bilirubin ◽  
Near Term

A 36-week gestation newborn was admitted to the neonatal intensive care unit for treatment of primary pulmonary hypertension and possible sepsis. The infant developed hyperbilirubinemia on day 4 of life and peaked on day 5 at a total serum bilirubin of 19 mg/dL. Phototherapy was started on day 4 and continued for 5 days. On day 8 of life, ibuprofen was started for fever; a concurrent total serum bilirubin was 15.7 mg/dL. The subsequent hospital course was uneventful, and discharge occurred on day 22 of life. Because the patient failed a hearing screen at discharge, he was referred for a diagnostic audiology workup. He subsequently failed formal audiometric testing on two occasions one week apart, and was given a diagnosis of auditory dys-synchrony and/or auditory neuropathy, consistent with kernicterus. At 5½ months of age, he was reported to be hypotonic and to have frequent arching movements. Since the total serum bilirubin did not exceed 19 mg/dL, concern was raised that ibuprofen may have caused displacement of bilirubin from its albumin binding site, resulting in kernicterus due to excessive unbound bilirubin concentrations. Ibuprofen should be administered with caution in preterm infants at risk for kernicterus.

YELLOW SKIN A BETTER PREDICTOR?

PEDIATRICS ◽  
1989 ◽  
Vol 84 (6) ◽  
pp. A45-A45
Author(s):  
Student
Keyword(s):  
Brain Damage ◽  
Clinical Utility ◽  
Serum Bilirubin ◽  
High Serum ◽  
Bilirubin Concentration ◽  
Yellow Colour ◽  
The Brain ◽  
Reserve Albumin ◽  
High Serum Bilirubin ◽  
Serum Bilirubin Concentration

If kernicterus develops in an infant due to high serum bilirubin, low reserve albumin, and acidosis, bilirubin acid will also be deposited in the skin. In consequence, it seems possible that the yellow colour of the skin is correlated with that of the brain, to the extent that bilirubin deposition in the skin has occurred by precipitation of bilirubin acid. If so, the intensity of the yellow colour of the skin may be a somewhat better predictor of brain damage than the serum bilirubin concentration and measurement of the colour of the skin may theoretically be of clinical utility.

Determination of Unbound Bilirubin in the Serum of Newborns

1974 ◽  
Vol 20 (7) ◽  
pp. 783-789 ◽  
Author(s):  
Jorgen Jacobsen ◽  
Richard P Wennberg
Keyword(s):  
Binding Capacity ◽  
Newborn Infants ◽  
Albumin Binding ◽  
Initial Oxidation ◽  
High Affinity ◽  
Normal Human ◽  
Unbound Bilirubin ◽  
Rate Limiting

Abstract An enzymatic assay is described for non-albuminbound bilirubin in the serum of newborn infants. Unbound bilirubin is oxidized to colorless compounds by ethyl hydroperoxide in the presence of horseradish peroxidase (EC 1.11.1.7), while albumin-bound bilirubin is protected from oxidation. Because the equilibrium between albumin and bilirubin occurs rapidly, the oxidation step is rate limiting, and the initial oxidation velocity of total bilirubin is proportional to the unbound bilirubin concentration. By titrating serum with bilirubin in vitro, the association constant and binding capacity of high-affinity sites for albumin binding can be determined. Normal human serum albumin tightly binds 1 mole of bilirubin per mole of albumin (binding constant, 2-4 x 108 liter/mol). Although weaker secondary binding occurs, the unbound bilirubin fraction increases rapidly after the high-affinity binding sites are saturated. Compromised newborns may have a decreased apparent binding capacity and (or) binding affinity. The method can be used to assess the risk of a jaundiced infant for bilirubin encephalopathy.

The Effect of Drugs on Albumin Binding of Bilirubin and on Free Bilirubin Concentration as Determined by Fluorescence Quenching

1979 ◽  
Vol 13 (9) ◽  
pp. 498-503
Author(s):  
John H. Drew ◽  
Rhondda Wells
Keyword(s):  
Fluorescence Quenching ◽  
Binding Affinity ◽  
Newborn Infant ◽  
Total Bilirubin ◽  
Binding Capacity ◽  
Albumin Binding ◽  
Binding Parameters ◽  
Bilirubin Concentration ◽  
Phenytoin Sodium ◽  
Clinically Significant

Fluorescence quenching was used to determine the influence of five drugs commonly used in the newborn infant, on the binding of bilirubin to albumin, and to quantitate the resultant changes in binding parameters and the free bilirubin concentration. The five drugs studied were digoxin, furosemide, diazepam, phenytoin sodium, and theophylline. The primary influence of digoxin, furosemide, diazepam, and phenytoin sodium was on the affinity of albumin to bind bilirubin. They also affected the capacity of albumin to bind bilirubin, but to a lesser extent. Furosemide reduced the apparent binding affinity by 60 percent (p = 0.01), phenytoin sodium by 58 percent (p < 0.01), digoxin by 52 percent (p = 0.02), and diazepam by 45 percent (p = 0.03). Furosemide reduced the apparent binding capacity by 24 percent (p < 0.001), digoxin by 23 percent (p = 0.04), and diazepam by 13 percent (p = 0.10). Phenytoin sodium had a different effect on the apparent binding capacity: It increased the apparent capacity by 30 percent (p < 0.01). Theophylline had no significant effects on either binding affinity or capacity or free bilirubin concentration. Furosemide, digoxin, and diazepam significantly increased free bilirubin concentration at all total bilirubin concentrations; therefore, these drugs should be used with caution in the jaundiced newborn infant. Phenytoin sodium increased free bilirubin concentrations in the low total bilirubin ranges only; however, the increase was marginal and unlikely to be clinically significant.

Is bilirubin/albumin ratio correlated with unbound bilirubin concentration?

2011 ◽  
Vol 54 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Yumi Sato ◽  
Ichiro Morioka ◽  
Akihiro Miwa ◽  
Tomoyuki Yokota ◽  
Kiyomi Matsuo ◽  
...  
Keyword(s):  
Bilirubin Concentration ◽  
Albumin Ratio ◽  
Unbound Bilirubin
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