Heterogeneity of F cells in β-thalassemia

BACKGROUND: Fetal hemoglobin (HbF), which is largely replaced after birth by the adult Hb, is concentrated in a few F cells. Their number significantly increases in certain physiologic and clinical situations, including in -thalassemia (-thal). Their quantification is used to detect fetalmaternal hemorrhage (FMH), where fetal cells enter the maternal circulation. We were confronted with a pregnant woman with -thal who was suspected to have FMH. To establish the usefulness of a flow cytometric procedure to differentiate between fetal cells and the maternal F cells, we screened adult -thal patients. STUDY DESIGN AND METHODS: Blood samples were simultaneously stained with fluorescent antibodies to HbF and to carbonic anhydrase (CA) isotype II, which is specific to adult red blood cells (RBCs). RESULTS: A heterogeneous distribution of RBCs with respect to HbF and CA expression was observed: adult non-F cells (CA+HbF) and F cells (CA+HbF+/HbF++) as well as F cells with characteristics of fetal cells (CAHbF++). CONCLUSIONS: The presence of CAHbF++ RBCs in nonpregnant women, and even men, with thal indicates that the CA/HbF method is inappropriate for detection of FMH. The coexistence of F cells carrying fetal or adult markers suggests that they originate from two types of stem cell, adult and fetal, lineages. Normally, the fetal lineage is insignificant, but in -thal, as HbF-containing RBCs have a selective advantage, the fetal lineage gains significance.