Understanding, detecting, and managing the “late” anemia of hemolytic disease of the fetus and newborn

The “late” anemia of hemolytic disease of the fetus and newborn (HDFN), first described over 65 years ago, remains incompletely understood and inconsistently treated. We suspect that deficiencies in understanding its pathogenesis and fostering uniformity in its management could be remedied by teams working collaboratively to test the best ideas through multicentered trials. We begin this review by proposing a data-based definition of anemia, and of “severe” anemia, among infants at birth and during the neonatal period. We then review early as well as recent reports of the “late” anemia of HDFN, suggesting that two pathogenic forms of the condition exist; hemolytic vs. non-hemolytic (hypoproductive). We then review the use of a noninvasive and rapid means of differentiating between these two possibilities, in any given case. Next, we review means of either preventing the “late” anemia or treating it without red blood cell transfusions, using erythropoietic stimulating agents (darbepoetin or erythropoietin). We present our preferred method, using darbepoetin, and explain what we see as the chief advantages. We call for the development of transfusion stewardship programs in each NICU, to establish NICU transfusion guidelines, periodically evaluate compliance, and provide advice for problem cases. In addition, these programs can endorse a consistent approach to managing neonates with HDFN, during their NICU stay and for the weeks after discharge. We end the review with a gap analysis and a call for new focused research aimed at producing better outcomes for these patients, and less uncertainty and stress for these families.