Related Experiment Videos
Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants
Insights
Intravenous vitamin E (E-Ferol) caused a fatal syndrome in infants, marked by liver injury, kidney dysfunction, and low platelets. This vasculocentric hepatotoxicity resulted from prolonged exposure to the supplement.
Area of Science:
- Pediatric Medicine
- Toxicology
- Gastroenterology
Background:
- A fatal syndrome occurred in infants receiving intravenous vitamin E (E-Ferol).
- E-Ferol contains dl-alpha-tocopheryl acetate solubilized with polysorbates.
Purpose of the Study:
- To investigate the clinical course and pathological findings in infants who developed a fatal syndrome after receiving E-Ferol.
- To identify potential causative factors and mechanisms of toxicity.
Main Methods:
- Clinical review of 36 infants from an index nursery who received E-Ferol.
- Autopsy tissue analysis from 20 infants who received intravenous vitamin E.
- Correlation of clinical outcomes with E-Ferol dosage and duration of exposure.
Main Results:
- Eight of 36 infants developed the syndrome, characterized by thrombocytopenia, renal dysfunction, cholestasis, and ascites.
- Affected infants had lower birth weight and received higher doses of E-Ferol for longer periods.
- Hepatic histology showed progressive injury, including Kupffer cell exfoliation, cellular debris accumulation, congestion, cholestasis, venule inflammation, and sinusoidal veno-occlusion.
Conclusions:
- The syndrome is linked to E-Ferol administration.
- Vasculocentric hepatotoxicity, resulting from cumulative effects of E-Ferol constituents, is proposed as the underlying mechanism.
- Lower birth weight infants may be at higher risk.
Abstract:
A fatal syndrome characterized by progressive clinical deterioration with unexplained thrombocytopenia, renal dysfunction, cholestasis, and ascites developed in certain infants throughout the United States who had received E-Ferol, an intravenous vitamin E supplement. We reviewed the clinical course of all 36 infants from one (index) nursery who had received E-Ferol, which contains 25 units per milliliter of dl-alpha-tocopheryl acetate solubilized with 9% polysorbate 80 and 1% polysorbate 20. The syndrome was recognized in eight of the 36 infants; affected infants had a lower birth weight (less than 1,200 g) and had received a higher total dose of E-Ferol for longer periods than the unaffected cases. We reviewed autopsy-derived tissue from 20 infants (six from the index nursery and 14 from three other collaborating nurseries) who had received the intravenous vitamin E preparation in a reported dose of 25 to 137 units/kg/day for six to 45 days between October 1983 and March 1984. The hepatic histology in the affected cases indicated a progressive injury characterized initially by Kupffer cell exfoliation, central lobular accumulation of cellular debris, and centrally accentuated panlobular congestion. Prolonged exposure to E-Ferol was associated with progressive intralobular cholestasis, inflammation of hepatic venules, and extensive sinusoidal veno-occlusion by fibrosis. We propose that vasculocentric hepatotoxicity is the basis for the observed clinical syndrome that represents the cumulative effect of one or more of the constituents of E-Ferol.