(P-TA-3) Comparison of Isovolemic Hemodilution Red Cell Exchange (IHD-RCE) to Standard Red Cell Exchange (STD-RCE) in Sickle Cell Disease: A Systematic Literature Review

Background/Case Studies:
Isovolemic hemodilution red blood cell exchange (IHD-RCE) (as compared to standard, or STD-RCE) may offer benefits of either a savings in per-procedure RBC use or attainment of a lower Fraction of Cells Remaining (FCR). IHD-RCE may offer an ‘iron unloading’ benefit among patients with iron overload. However, the evidence supporting these contentions is limited. We therefore sought to review the published literature to explore whether these benefits have been realized in real-world settings.

Study

Design/Methods:
A literature search was conducted using the following terminology: ("sickle cell disease"[MeSH] OR "sickle cell anemia") AND ("isovolemic hemodilution" OR "red cell exchange" OR "automated erythrocytapheresis") AND ("iron overload" OR ferritin OR "iron burden") AND (“safety” OR “tolerability” OR “complications” OR "adverse effects") AND (“technique” OR “protocol” OR “procedure”). Additional studies were identified through bibliography review. Inclusion criteria included clinical studies comparing outcomes between STD-RCE and IHD-RCE. Data including procedure intervals, pre-Hb S%, actual FCR, RBC utilization, and ferritin levels were extracted and analyzed using descriptive statistics.

Results/Findings:
The initial search and bibliography review resulted in 70 studies; 48 studies were excluded for not meeting inclusion criteria. The remaining 22 were screened by title and abstract review leaving 10 finalists, of which 3 reports met full inclusion criteria and were retained for data extraction. These reports described 35 patients (18 females, 17 males) with 28/35 (80%) undergoing RCE for secondary stroke prevention. Comparing STD-RCE vs IHD-RCE, we found no difference in intervals (in days) among 15 patients for whom discrete data was provided - 30 (21-67) vs 31 (21-43), p=0.52; pre HbS (%) – 41 (21-58) vs 41 (25-54), p=0.69; or actual FCR (%) – 24 (18-51) vs 26 (16-44), p=0.76. Among these patients, there was a reduction in RBC utilization (mL/mL Total Blood Volume) – 0.55 (0.42-0.66) vs 0.49 (0.34-0.54), p=0.02. In another report, 6 patients had an increased interval when converting from STD-RCE to IHD-RCE – 37.0 ± 7.0 vs 52.9 ± 6.5 (p < 0.001); and among 20 patients a reduction in RBC utilization (mL/kg) 39.5 ± 4.6 vs 35.5 ± 4.1, p< 0.001) was reported. Among 26 patients for whom ferritin levels were presented, a clear reduction was not observed (data not shown). Furthermore, no clear safety signals were observed.

Conclusions:
Conversion to IHD-RCE appears to reduce per-procedure RBC utilization, may permit prolongation of RCE intervals, and appears safe, but does not appear to have an iron-unloading benefit over STD-RCE.