A Comparison of Chronic Manual and Automated Red Blood Cell Exchange Transfusion in Sickle Cell Disease Patients From Two Comprehensive Care Centres in the United Kingdom

Abstract 3430

Chronic transfusion is indicated in the treatment and prevention of sickle cell disease (SCD) related-complications. Red blood cell exchange (RBCX) is preferred over top-up transfusion as it enables iron balance and rapid reduction of sickle hemoglobin (HbS) without increasing blood viscosity. RBCX can be done manually by sequential phlebotomy and transfusion or by automated apheresis, but the two methods have not been formally compared. Bart's Health NHS Trust (BHT) performs manual RBCX and Guy's and St. Thomas NHS Trust (GSTT) automated RBCX. Manual RBCX consists of isovolumetric exchange 15 to 20 mL/kg of venesected blood for normal saline and packed RBC, generally at a 1:1 ratio. Automated RBCX utilizes the Spectra Optia Apheresis System with a fractional cell remaining between 24 and 44, end Hct within 0.02 of pre-RBCX Hct, and a fluid replacement balance of 100%. The indications for RBCX and pre-RBCX HbS or hemoglobin SC (HbSC) target (30% or 50%, depending on indication) are the same in both units. All packed RBC were leukodepleted, HbS negative, ≤ 7 days old, and phenotypically matched for C, D, E, and Kell.

A retrospective observational cohort study as part of a quality assurance audit was conducted examining all SCD patients attending regular RBCX at BHT and GSTT between 1 May 2011 and 30 April 2012. Fifty-one patients (21 manual, 30 automated), totaling 401 RBCX sessions were included. Ten patients in the manual group and 7 patients in the automated group targeted an HbS of < 30%, while the rest were targeted to < 50%. There was no significant difference in baseline characteristics between the two groups. Peripheral vein was the most common method of cannulation in manual RBCX while temporary central venous catheterization was most common in automated RBCX (P < 0.0001). Time interval differed between manual and automated RBCX (median 4.4 vs. 7.1 weeks, P < 0.0001). Both groups consistently achieved a post-RBCX Hct < 0.350. More patients on automated RBCX were able to consistently achieve their prescribed HbS or HbSC target (defined as > 2/3 of RBCX sessions) than on manual RBCX (37% vs. 10%, unadjusted OR 5.5, 95% CI 1.07 – 28.22, P = 0.048). When adjusted for the prescribed pre-RBCX HbS or HbSC target, the Mantel-Haenszel OR estimate was 4.72 (95% CI 0.885 – 25.17). Older age was also associated with consistently achieving the prescribed HbS or HbSC target (P = 0.010 on multivariable logistric regression). Although the yearly volume of RBC and donor units used were significantly higher in the automated group (241.1 mL/kg/year and 55 units/year) compared to the manual group (127 mL/kg/year and 32 units/year), there was no difference in the rate of allo-antibody formation. There was no difference in the mean ferritin trend between manual and automated RBCX in non-chelated patients (−0.068 ± 1.439 vs. −0.297 ± 2.027 ug/L/day, P = 0.439). Automated RBCX was better at maintaining a near zero iron balance than manual RBCX due to considerable individual variability in the manual group (kurtosis statistic 13.221 ± 0.935 SE vs. 0.398 ± 1.121 SE). It took a significantly longer time to perform a manual RBCX session than an automated one (257 min. vs. 115 min.). There was no significant difference in the number of adverse events. The number of RBCX sessions that had to be converted to top-up transfusions in the manual group because of low pre-RBCX haematocrit far exceeded that of the automated group (11 vs. 0 sessions). None of the patients in either group had new or progressive neurological events.

Manual RBCX, despite an optimized protocol and strict adherence to treatement, is inferior to automated RBCX in being able to consistently achieve the prescribed HbS target, although consistent adherence with automated RBCX can also be challenging. Automated RBCX requires less time to perform than manual RBCX, but involves higher RBC use and more donor exposure. Adverse events and antibody formation are the same for both methods. Automated RBCX can maintain a near zero iron balance in most patients without the use of iron chelation and with less individual variability than manual RBCX. The results suggest that automated RBCX is the preferred RBC exchange method in controlling HbS in SCD patients. Further longitudinal study is required to determine whether a better control of HbS translates into differences in patient-related outcomes.