Etiology of red blood cell macrocytosis during childhood: Impact of new diseases and therapies

Although an elevated erythrocyte mean corpuscular volume has been noted in many conditions, the relative frequency of various causes of macrocytosis in the pediatric population has not been defined. Therefore, the different medical conditions associated with red cell macrocytosis were retrospectively reviewed. One hundred forty-six children between 6 months and 12 years of age with a mean corpuscular volume ≥ 90 fL were identified during a 13-month period. The most common association with macrocytosis was drug ingestion (anticonvulsants, zidovudine, immunosuppressive agents), observed in 51 (35%) of the cases. Other conditions associated with macrocytosis were congenital heart disease (20), Down syndrome (12), reticulocytosis (11), and marrow failure/myelodysplasia (6). Miscellaneous diseases were identified in 21 children. Twenty-four cases had no apparent cause of their macrocytosis; 21 of them had just a slight elevation of the mean corpuscular volume (91 or 92 fL), suggesting that these values probably represent the upper limit of normal. No cases of vitamin B₁₂ or folate deficiency were observed. The use of relatively new drugs such as valproate, zidovudine, and immunosuppressants (for the treatment of diverse medical conditions) accounted for more than half of the cases of drug administration and 24% of the children with macrocytosis. Three children with bone marrow failure had macrocytosis and pancytopenia, suggesting that this finding might be the first manifestation of serious but treatable disorders such as aplastic anemia.