Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants
K. E. Bove, N. Kosmetatos, K. E. Wedig, D. J. Frank, S. Whitlatch, V. Saldivar, J. Haas, C. Bodenstein and W. F. Balistreri
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.
