Post-exchange neutrophil count, but not post-hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange

BackgroundWith chronic transfusion in sickle cell disease (SCD), equipoise exists regarding whether increasing the post-procedure hematocrit (Hct) suppresses endogenous erythropoiesis. Reticulocytosis predicts SCD morbidity and mortality, so this study's objective was to clarify the role of the post-procedure Hct in suppressing reticulocytosis and to identify other potential red cell exchange (RCE) parameters predictive of reticulocytosis.Study Design and MethodsThis retrospective analysis of 17 patients who underwent chronic RCE at a single institution between 2014 and 2022 examined both standard red cell exchanges (SRCE) and exchanges preceded by isovolemic hemodilution (IVH-RCE). Post-procedure parameters with biologic plausibility to influence the subsequent procedure's absolute reticulocyte count (sPre-ARC) were examined using regression modeling.ResultsNeither post-hematocrit, nor post-hemoglobin (Hb), nor Delta Hb/day was associated with sPre-ARC or the change in HbS% per day (Delta HbS%/day). Concurrent Hb was predictive for SRCE but not IVH-RCE, where ARC trended lower than with SRCE. Male gender and post-procedure neutrophil and white cell counts were predictors of sPre-ARC, consistent with their associations with SCD morbidity and mortality. IVH-RCE had a stronger correlation than standard RCE between pre-Hct and neutrophil or white cell depletion.DiscussionAlthough targeting a post-procedure Hct maintains a higher subsequent pre-procedure Hb and a lower sPre-HbS%, it does not lead to sustained suppression of reticulocytosis as measured by the sPre-ARC or the Delta HbS%/day. IVH-RCE or the addition of hydroxyurea could be considered in those patients with high reticulocyte, white blood cell, or neutrophil counts.