Increased Reticulocytosis during Infancy Is Associated with Increased Hospitalizations in Sickle Cell Anemia Patients during the First Three Years of Life

Abstract

ObjectiveAmong older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days.Study DesignData from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy and childhood.ResultsA majority of subjects had demonstrable anemia with increased reticulocytosis. Only increased absolute reticulocyte levels during early infancy were associated with a significant increase in hospitalization during the first three years of life. Higher absolute reticulocyte counts were also associated with a markedly shorter time to first hospitalizations and a four-fold higher cumulative frequency of clinical manifestations over the first three years of life. No significant increase in white blood cell counts was identified among the infant subjects.ConclusionsThese data suggest that during early infancy, increased reticulocytosis among asymptomatic SCA subjects is associated with increased severity of disease in childhood.

Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the CooperativeStudy of SickleCellDisease

“…[1] Consistent with a previous report from the BABY HUG study, [6] those infants in the lowest quartile for hemoglobin had the highest event rate of the four hemoglobin groups, while there was no statistical difference in event rates between the four groups divided by steady state WBC count. The rate of stroke and death increased in a step wise fashion with increasing ARC, but there was not a consistent decrease in the number of events as the hemoglobin increased which would limit the utility of using hemoglobin as a risk stratification marker in young infants.…”

“…Demographic and hematologic data for each ARC quartile are shown in Table 1 and are consistent with previous reports. [1,5]…”

“…The association of infant reticulocytosis with painful crisis, acute chest syndrome and other SCA-related complications were studied previously using a modern cohort of infants with sickle cell disease. [1] However, the two most severe outcomes of SCA, stroke and death, were not present in that cohort. Therefore, archived data from the CSSCD cohort was analyzed to determine if early ARC could identify those pediatric SCA patients who are at the highest risk of stroke or death.…”

“…Recently, in a single-center pilot study, steady state absolute reticulocyte count (ARC), but not hemoglobin or white blood cell (WBC) count, during early infancy was associated with an increased rate of early hospital admission for painful crisis, acute chest syndrome and splenic sequestration. [1] Infants with increased levels of reticulocytosis were hospitalized at an earlier age and had a four-fold higher cumulative frequency of hospitalizations during the first three years of life. None of the enrolled infants in the study died or had a stroke, arguably the two most severe complications of SCA.…”

“…None of the enrolled infants in the study died or had a stroke, arguably the two most severe complications of SCA. [1] In a separate study, reticulocytosis at the time of Transcranial Doppler (TCD) screening (median age 6.2 years, range 2.0–11.2 years) was correlated with cerebrovascular disease in a cohort of Brazilian SCA patients. [2]…”