More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Background: In sickle cell disease (SCD), red blood cells (RBCs) containing hemoglobin S can be denser than RBCs containing wild-type hemoglobin, especially when dehydrated. We hypothesize that targeting denser RBCs during red blood cell (RBC) exchange for SCD could result in more efficient removal of dehydrated, sickled RBCs and preservation of non-sickled RBCs. Study design and methods: Waste products from RBC exchanges for SCD were used as “simulated patients”. One RBC volume was exchanged using ABO-compatible blood. The apheresis instrument was programmed to exchange the entire RBC layer by indicating the hematocrit (control), or the bottom half by indicating the hematocrit was half the hematocrit (experimental), with or without subsequent transfusion. Hemoglobin S levels, and complete blood counts were measured. Results: Hemoglobin S levels were lower after the modified versus control RBC exchange (post-RBC exchange mean 4.96% and 11.27%); total hemoglobin S amounts were also lower (mean 19.27 and 58.29 mL of RBCs). Mean RBC density decreased after the modified RBC exchange by 8.86%. Hematocrit decreased in the modified RBC exchange by 36.37%, with partial correction by direct transfusion following a truncated RBC exchange. Conclusions: Targeting denser RBCs in RBC exchange enhanced hemoglobin S removal and decreased RBC density. Further development of this ex vivo model could potentially allow for: 1) improved reduction in hemoglobin S levels (allowing for longer periods between RBC exchange or maintained lower levels), or 2) achievement of previous goal hemoglobin S levels with fewer donor units (reducing alloimmunization risk and improving blood utilization).