vessel with red blood cells
Inside space of empty healthy human anatomical vessel with red blood cells – erythrocytes and endothelium cells, 3d rendering

A study published in Transfusion characterized the adverse events (AEs) experienced by children with sickle cell disease (SCD) who underwent automated red cell exchange (RCE) and further revealed the preprocedure factors that lead to a higher risk of experiencing them.

This retrospective review analyzed data from 38 pediatric patients who received RCE in a period of 3 years, demonstrating that AEs were more frequently experienced in patients with a hematocrit above or equal to 30%, systolic blood pressure above the 50th percentile, severe central nervous system vasculopathy, and other hemoglobinopathies with non-sickle cell anemia genotypes. 

From a total of 760 procedures studied, 150 (19.7%) lead to AEs, out of which 45% were symptomatic. In order of frequency, patients reported dizziness, nausea, diaphoresis, and syncope. As for the asymptomatic AEs, hypocalcemia was the most common, followed by hypotension.

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This finding carries clinical importance, as noted by the authors, who wrote “based on the high incidence of procedural hypocalcemia, we advocate for routine serial ionized calcium monitoring and continuous IV calcium replacement to minimize symptomatic AEs from occurring.” Additionally, while rare, allergic and febrile reactions were also seen in 9 and 5 procedures, respectively. 

Interestingly, although isovolemic hemodilution (IHD) was not linked to higher AEs, the authors mentioned a previous study that found citrate and vasovagal reactions were predominantly experienced by patients who underwent IHD-RCE. Noticing the small sample size is a limitation of both studies, they still suggest IHD may be safe, and the risk for developing such AEs is likely minimal.

“However, due to a paucity of studies investigating the overall safety of IHD-RCE compared with conventional RCE, the [2020 American Society of Hematology] clinical guidelines panel highlighted a need for further studies evaluating the safety of IHD-RCE in chronically transfused SCD patients,” the authors concluded.

Automated RCE represents a valuable therapeutic tool for patients with SCD, playing a pivotal role in primary and secondary stroke prevention, currently preferred over partial manual exchange and simple transfusion. While its benefits cannot be overlooked, understanding the AEs associated with the procedure allows a more individualized approach for each patient by increasing vigilance of asymptomatic AEs and modulating RCE in patients with risk factors for overall AEs.


Wade J, Yee MEM, Easley KA, et al. Procedural adverse events in pediatric patients with sickle cell disease undergoing chronic automated red cell exchange. Transfusion. Published online January 24, 2022. doi:10.1111/trf.16807