Enrichment of Erythrocytes of Fetal Origin From Adult-Fetal Blood Mixtures via Selective Hemolysis of Adult Blood Cells: An Aid to Antenatal Diagnosis of Hem oglobinopathies

Red cell lysis in isotonic solutions containing NH4CI, NH4HCO3, and a carbonic anhydrase enzyme inhibitor (acetazolamide) is a function of erythrocyte enzyme activity and permeability of cells to the inhibitor. Erythrocyte carbonic anhydrase activity is at least fivefold greater and acetazolamide permeability about tenfold less for adults than for newborns. In this setting, > 99.9% of red cells from adults can be hemolyzed at a time when > 25% of those from newborns remain intact. This easily applied method may be useful when antenatal diagnosis of hemoglobinopathies is otherwise precluded by contamination with maternal erythrocytes. The feasibility of differential hemolysis via NH4CI-HC03-mediated, acetazolamide-modulated reactions is shown by the successful isolation of the few fetal-origin erythrocytes present in grossly nonbloody amniotic fluids and, in one instance, by approximately 3300-fold enrichment of apparently authentic fetalorigin red cells from the arm blood of a woman in her 18th wk of pregnancy.