Blood, 15 March 2002, Vol. 99, No. 6, pp. 2017-2022
HEMATOPOIESIS
Infant hypervitaminosis A causes severe anemia and
thrombocytopenia: evidence of a retinol-dependent bone marrow cell
growth inhibition
Silverio Perrotta,
Bruno Nobili,
Francesca Rossi,
Maria Criscuolo,
Achille Iolascon,
Daniela Di Pinto,
Irene Passaro,
Lucia Cennamo,
Adriana Oliva, and
Fulvio Della
Ragione
From the Department of Pediatrics, Department of
Biochemistry and Biophysics "F. Cedrangolo," Second University of
Naples, Naples, Italy; and the Institute of Pediatrics, University of
Foggia, Foggia, Italy.
Vitamin A is a pivotal biochemical factor required for normal
proliferation and differentiation as well as for specialized functions,
such as vision. The dietary intake of 1500 IU/day is recommended in the
first year of life. Here, we report the case of an infant who had been
given 62 000 IU/day for 80 days. The infant showed several clinical
signs of retinol intoxication, including severe anemia and
thrombocytopenia. Bone marrow showed a remarkably reduced number of
erythroid and megakaryocytic cells. The interruption of vitamin A
treatment was immediately followed by clinical and biochemical
recovery. To clarify whether the effects of retinol are due to a direct
action on bone marrow cell proliferation, we investigated the activity
of retinol (both the drug and the pure molecule) on the growth of
K-562, a multipotent hematopoietic cell line, and on bone marrow
mesenchymal stem cells. We observed that vitamin A strongly inhibited
the proliferation of the cells at concentrations similar to those
reached in vivo. Subsequent biochemical analyses of the cell cycle
suggested that the effect was mediated by the up-regulation of
cyclin-dependent kinase inhibitors, p21Cip1 and
p27Kip1. These are the first findings to demonstrate that
infant hypervitaminosis A causes a severe anemia and thrombocytopenia
and that this is probably due to the direct effect of the molecule on
the growth of all bone marrow cellular components. Our data also
suggest potential bone marrow functional alterations after excessive
vitamin A intake because of emerging social habits.
