L. Defranceschi et al., ORAL MAGNESIUM SUPPLEMENTS REDUCE ERYTHROCYTE DEHYDRATION IN PATIENTSWITH SICKLE-CELL DISEASE, The Journal of clinical investigation, 100(7), 1997, pp. 1847-1852
Intracellular polymerization and sickling depend markedly on the cellu
lar concentration of sickle hemoglobin (Hb S). A possible therapeutic
strategy for sickle cell disease is based on reducing the cellular con
centration of Hb S through prevention of erythrocyte dehydration. The
K-Cl cotransporter is a major determinant of sickle cell dehydration a
nd is inhibited by increasing erythrocyte Mg content. We studied 10 pa
tients with sickle cell disease before treatment and after 2 and 4 wk
of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hema
tological parameters, erythrocyte Na, K, and Mg content, erythrocyte d
ensity, membrane transport of Na and K, and osmotic gradient ektacytom
etry were measured. We found significant increases in sickle erythrocy
te Mg and K content and reduction in the number of dense sickle erythr
ocytes. Erythrocyte K-Cl cotransport was reduced significantly. We als
o observed a significant reduction in the absolute reticulocyte count
and in the number of immature reticulocytes. Ektacytometric analysis s
howed changes indicative of improved hydration of the erythrocytes. Th
ere were no laboratory or clinical signs of hypermagnesemia. Mild, tra
nsient diarrhea was the only reported side effect. We conclude that or
al Mg supplementation reduces the number of dense erythrocytes and imp
roves the erythrocyte membrane transport abnormalities of patients wit
h sickle cell disease.