Abstract Background Isovolemic hemodilution red cell exchange (IHD‐RCE) (as compared to standard, or STD‐RCE) may: reduce per‐procedure RBC use, result in a lower fraction of cells remaining (FCR), and provide an “iron unloading” benefit. We review the published literature to explore whether these benefits have been realized in real‐world settings. Methods A literature search was conducted in PubMed, Embase, EBSCOhost, and Cochrane Library. Additional studies were identified through bibliography review. To be included, studies required STD‐RCE versus IHD‐RCE comparison groups. Data, including RBC utilization, actual FCR, ferritin levels, pre‐hemoglobin S% (HbS%), and procedure intervals were extracted and analyzed using descriptive statistics. Results The initial search and bibliography review yielded 70 studies; 48 were excluded for not meeting inclusion criteria; of the remainder, 3 reports met full inclusion criteria and were retained for data extraction. Compared to STD‐RCE, IHD‐RCE reliably reduced red cell requirements, with reduction (in mL/mL Total Blood Volume) from 0.55 (0.42–0.66) to 0.49 (0.34–0.54), among 15 patients ( p = 0.02); and (in mL/kg) from 39.5 ± 4.6 to 35.5 ± 4.1 ( p < 0.001) in another 20 patients. While actual FCR was lower than programmed FCR with both STD‐RBCx and IHD‐RBCx, the magnitude of this difference was not significantly different ( n = 15). Among 26 patients for whom ferritin levels were reported, a clear reduction was not observed. Furthermore, no clear safety signals were observed. Conclusions Conversion to IHD‐RCE appears safe and reduces per‐procedure RBC utilization by approximately 1 unit. IHD‐RCE did not demonstrate a clear iron‐unloading benefit over STD‐RCE.
Nourse et al. (2026) studied this question.