VALPROIC-ACID-INDUCED ALTERATION IN RED-CELL MEMBRANES

Erythrocyte macrocytosis is noted in patients taking valproate with se rum levels >100 mug/ml. We postulated valproate affects membrane struc ture directly by altering membrane phospholipids. Patients were select ed from a chronic care facility, had known static encephalopathy, were generally healthy, and on valproate monotherapy. Red cells were obtai ned from three groups: macrocytic with serum levels >100 mug/ml (Group 1), normocytic with serum levels <100 mug/ml (Group 2), and controls (Group 3). Patients in Group 2 demonstrated the highest level of membr ane phospholipid content. Patients in Group 1 demonstrated total phosp holipid content lower than controls. Phospholipid analysis demonstrate d higher sphingomyelin and significantly lower phosphatidylserine in G roup 1 than in Groups 2 or 3. Phosphatidylcholine and phosphatidyletha nolamine did not significantly differ among the three groups. Valproat e appears to alter the membrane matrix directly by affecting total pho sphatidylserine and sphingomyelin contents. This effect is serum-conce ntration-specific, occurring when levels are >100 mug/ml. Macrocytosis may be reflective of this biochemical, concentration-specific effect.