More Efficient Exchange of Sickle Red Blood Cells can be Achieved by Exchanging the Densest Red Blood Cells
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1 More Efficient Exchange of Sickle Red Blood Cells can be Achieved by Exchanging the Densest Red Blood Cells Thibodeaux, SR, Jamensky, L, Schell K, Irwin L, O Doherty U Hospital of the University of Pennsylvania Department of Pathology and Laboratory Medicine Division of Transfusion Medicine and Therapeutic Pathology
2 Sickle Cell Disease Prevalence in the USA 100,000 people affected 1/365 Black or African- American births 1/13 have sickle cell trait Pathogenesis Autosomal recessive disease Point mutation causes glutamic acid valine
3 Sickle Cell Disease has Major Health Implications Complications Acute Chronic Cost cost for hospital stays due to SCD complications ~$488 million
4 Increased quantity, but what about quality of life?
5 Sickled Red Blood Cells are Denser than non-sickled Red Blood Cells Erythrocyte dehydration K+ efflux from the red blood cell Decreased intracellular water content Increased mean corpuscular hemoglobin concentration (MCHC) Can we capitalize on this density difference? Dense, Dehydrated Red Blood Cells (DRBCs) defined as having a density exceeding Increased rigidity, decreased stability Include a variable fraction of irreversibly sickled cells Non-sickle cell patient Sickle cell patient N Engl J Med Sep 11;337(11): Microcirculation (2004) 11, Blood. 2012;120(15):
6 Experimental Approach Control RCE Experimental RCE Waste Donor Plasma WBCs Patient Plasma WBCs RBCs RBCs Control settings (current practice) exchange the entire RBC layer based on the patient s hematocrit Patient RCE exchange waste product Donor therapeutic phlebotomy waste Waste Waste from this exchange Experimental settings exchanges the bottom half of the RBC layer based on the patient s hematocrit
7 Initial Findings support that targeting the densest RBCs leads to lower HgbS Control settings Experiment al settings Pre- RCE Percent Hgb S Reduction 23.2% Control Experimental Hgb S 23.7% 76.7% 94.5% Post- RCE Hgb S 5.4% Hgb S 1.3%
8 Better Reduction in Hemoglobin S is Reproducible
9 However, Reproducibility was not 100% In three experiments, there was no improvement by exchanging the bottom half of the hematocrit
10 Unexpected hurdles: Age of product tested Age of patient blood stored before exchange Density of RBCs may re-equilibrate with time due to K+ flux The experiments that did not work all used aged patient product MCHC s decrease over time in stored products Fresh product Old product (37 days old) Percent Decrease in HgbS
11 Unexpected hurdles: RBC depletion Hematocrit loss with experimental settings Taking more RBCs than we give back Average Percent Reduction 25% More than 50% of the RBCs are in the bottom half of the RBC layer J. Cell. Mol. Med. Vol 15, No 12, 2011 pp
12 Conclusions More effective red cell exchange in sickle cell anemia patients is possible by taking advantage the density gradient between sickled RBCs and normal RBCs Goals and applicability to patients 1) achieve a higher reduction in hemoglobin S in patients or 2) achieve the previous levels of reduction using fewer donor units Hurdles Hematocrit loss with experimental settings Patient variability in RBC density may lead to difficulty in identifying patients that will most benefit from the procedure and leads to difficulty in correcting the patient final hematocrit
13 Acknowledgements The nurses in apheresis Especially Clarice Dixon for saving donor units The Blood Bank Staff Especially Rachel Hauser for the training to make donor units and type blood The Stem Cell Lab Staff For measuring CBCs The hematology lab For Hemoglobin S measurements And our fine colleagues Nicole Aqui, Eric Russell, Carlos Villa
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