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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 β-thalassemia (β-thal). Their quantification is used to detect fetal–maternal hemorrhage (FMH), where fetal cells enter the maternal circulation. We were confronted with a pregnant woman with β-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 β-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 (CA–HbF++).

CONCLUSIONS: The presence of CA–HbF++ 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 β-thal, as HbF-containing RBCs have a selective advantage, the “fetal” lineage gains significance.