Significant variability in the duration of hemolysis among infants with hemolytic disease of the fetus and newborn (HDFN), alongside diverse causes for late anemia, according to preliminary results from a pilot study published recently in the Journal of Perinataology.
While hemolysis persisted for as long as 75 days in some cases, others normalized within a week. Late anemia occurred in four infants, with underlying mechanisms varying between hemolytic and non-hemolytic causes. These results provided early insights into the complexity of managing HDFN and the potential benefits of interventions such as erythropoietic stimulating agents.
Hemolysis in this study was assessed using serial end-tidal breath carbon monoxide (ETCOc) measurements, a marker of breakdown of red blood cells. All 13 infants showed elevated levels of ETCOc at birth, with gradual declines over time. In most cases, hemolysis fell below the normal threshold (<1.7 ppm) by one week, but in others, hemolysis persisted for several weeks, highlighting the variability in severity of disease. ETCOc patterns sometimes reflected maternal antibody load or response to exchange transfusions, but other factors contributing to variability remain unclear.
“Response to ESAs [erythropoietin stimulating agents] was variable. For example, of the four patients with HDFN due to antibody against Kell-1—an antigen expressed on the surface of RBC [red blood cell] precursors, three received ESA therapy, and two of those avoided late transfusion (one untreated anti-Kell-1 patient also avoided late transfusion),” the authors of this study explained. “In larger studies aimed at completely preventing late anemia, the optimal ESA, unit dose, dosing interval, and duration of dosing could be assessed.”
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Late anemia was observed in four cases, requiring red blood cell transfusions. In two instances, anemia was linked to ongoing hemolysis, evidenced by persistently elevated levels of ETCOc. However, two others showed normal levels of ETCOc, suggesting a non-hemolytic origin. For example, one infant’s serum erythropoietin level—a hormone responsible for red blood cell production—was abnormally low despite severe anemia, indicating potential disruptions in the body’s compensatory mechanisms.
Erythropoietic stimulating agents, such as darbepoetin and erythropoietin, were used in 10 infants, though not as part of the study protocol. These agents showed mixed effectiveness in preventing late anemia, with some infants avoiding late transfusions entirely while others still required intervention. The role of erythropoietic stimulating agents appeared promising, particularly for cases involving anti-Kell-1 antibodies, which may impair red blood cell precursors.
Although this study was small and limited by high variability in patient characteristics, it raises important questions about the mechanisms of late anemia and optimal management strategies for HDFN. Future research could explore the functional lifespan of maternal antibodies, refine dosing protocols for erythropoietic stimulating agents, and investigate other markers of progression of disease. For affected families, these findings emphasize the need for personalized treatment approaches and close monitoring during the first weeks of life.
