More Efficient Exchange of Sickle Red Blood Cells Can be Achieved By Exchanging the Densest Red Blood Cells

Background: In sickle cell disease, it is well established that cells containing two mutated hemoglobins (SS) are denser than cells containing wild-type hemoglobin. We asked whether we could more efficiently exchange red blood cells (RBCs) in sickle cell anemia patients by exploiting the denser property of RBCs containing hemoglobin SS compared to wild-type RBCs.

Methods: To probe this question, we performed a series of experiments using the waste bags from sickle cell patients as simulated patients. We exchanged the simulated patient with one RBC volume using recently expired ABO compatible RBC units on a COBE Spectra apheresis instrument. We measured hematocrit and hemoglobin S levels in the simulated and control patient bag before and after the exchange. In the experimental scenario, we programmed the COBE Spectra to exchange the bottom half of the RBCs by indicating that the hematocrit was half of the true hematocrit (e.g. 21% when the hematocrit of the bag was 42%). For control exchanges we programmed the COBE Spectra to exchange the entire RBC volume by programing the hematocrit to be the true one (for this example 42%).

Results: The percentage of hemoglobin S was more effectively diminished in our modified exchanges that targeted dense RBCs than in control exchanges. Our experimental exchanges were also more effective than expected for a 1 red blood cell volume exchange by Poisson calculation (n=5). In an optimized experiment, hemoglobin S was reduced from 23.7% to 1.3 % after exchanging 1 RBC volume using our modified approach while it was reduced from 23.2 to 5.4% using the control or routine exchange parameters. The same volume of donor RBCs (1 RBC volume) was used to exchange our experimental and control simulations. We obtained a 95% reduction of hemoglobin S in our experimental conditions and a 77% reduction in our control conditions. The instrument was programmed to compensate for RBC depletion with the modified RBC exchange. The compensation is necessary to maintain a constant hematocrit since more RBCs are present in the bottom half than top half of the centrifuged RBCs.

Conclusions: It is possible to exchange sickle cell anemia patients more effectively by taking advantage of the fact that RBCs containing hemoglobin SS are denser than normal RBCs. Using waste products from sickle cell anemia exchanges provides an opportunity to safely optimize exchange parameters. This approach should allow us to: 1) achieve a higher reduction in hemoglobin S in patients, 2) achieve the previous levels of reduction using fewer donor units and/or 3) combine red cell exchange with other therapies for sickle cell disease, such as hydroxyurea, by taking advantage of the differential densities and selective depletion of red blood cells containing different levels of hemoglobin F.