619 INHIBITORS OF HEME PRODUCTION IN TRANSIENT ERYTHRO-BLASTOPENIA OF CHILDHOOD

Abstract

Transient erythroblastopenia of childhood (TEC), congenital hypoplastic anemia (CHA), and iron deficiency anemia (IDA) are characterized by anemia, reticulocytopenia, and decreased eryth-ropoiesis. Differences in erythrocyte size, enzyme activities, membrane antigens, hemoglobin F, and protoporphyrin content; serum iron, iron-binding capacity, and ferritin levels; and spontaneous recovery from TEC are significantly diagnostic to differentiate these conditions. Inhibitors of heme production have not been found in CHA serum. To determine if inhibitors of heme production occur in TEC or IDA 1 ml human bone marrow cultures were incubated under controled conditions in pairs with and without erythropoietin (EPO) added. Fe59 was added to the cultures for the last 4 hours of incubation and EPO stimulated Fe59 heme production measured. To check for inhibitor activity, 1 μ1 of test serum was added to culture pairs. Serum from 8 untransfused TEC patients produced a 23±22% inhibition of Fe59 heme production. In contrast, serum from 2 untransfused CHA and 7 IDA children produced a 43±34% stimulation of Fe59 heme production. As recovery occurred, serial serum specimens from 2 TEC patients demonstrated gradual disappearance of inhibitor activity. We conclude that a transient inhibitor of heme production occurs in TEC but not in CHA or IDA. This inhibitor may an immune response and be the mechanism for anemia in TEC.