Conserving Red Blood Cell Units in the Treatment of Patients With SCD During Blood Shortages

The ongoing COVID-19 pandemic has led to severe blood shortages within the health care delivery system, disproportionately affecting the supply of red blood cells (RBCs) prophylactically matched for Rh and K antigens, which are recommended for the treatment of patients with hemoglobinopathies. Patients with sickle cell disease (SCD) requiring chronic red cell exchange (RCE) have a particularly large demand for RBC units.

A study published in Blood Advances investigating dual measures designed to conserve blood resources and use found that obtaining pretransfusion hemoglobin S (HbS) values prior to RCE may assist in determining exact RBC volume needed to achieve the necessary post-RCE HbS level. Additionally, the investigators found that increasing the RCE end hematocrit above the pretransfusion level reduced the required number of RBC units needed. These strategies led to an 18% reduction in transfused RBC units in patients with SCD who underwent chronic RCE during the COVID-19 pandemic while maintaining pretransfusion HbS percentage values.

“The ability to use nearly 20% fewer red cell units is a tremendous savings in this current national shortage, helping ensure all patients who need blood will have blood available to them.”

—Stella Chou, MD

“The ability to use nearly 20% fewer red cell units is a tremendous savings in this current national shortage, helping ensure all patients who need blood will have blood available to them,” said Stella Chou, MD, of Children’s Hospital of Philadelphia. “While raising the hematocrit can only be implemented as a short-term measure, having the pre-exchange hemoglobin quantification prior to the procedure can result in significant unit savings as well, by allowing precise calculation of red cells needed.”

Dr. Chou and colleagues enrolled 50 patients with SCD who were on a chronic RCE program. The mean age of the patients in the study was 23.5 years (range = 9-44).
Pretransfusion HbS goals for patients enrolled in the study were as follows:

  • <30% (n=33)
  • <35%-45% (n=8)
  • <50% (n=9)

Most commonly, transfusion therapy was indicated for primary stroke prevention (n=16) and secondary stroke prevention (n=23). The patients in the study cohort required RCE every three to five weeks with a corresponding RBC unit requirement ranging between two and 10 units.

The first studied strategy was the acquisition of pretransfusion HbS results by the start time of the procedure to calculate the exact RBC volume required to achieve a desired HbS after RCE. Secondly, the researchers modestly increased the targeted end hematocrit “to enhance suppression of endogenous erythropoiesis,” which was performed in 43% of procedures and for 11 patients.

Ultimately, this led to an increase of the fraction of cells remaining (FCR) needed to maintain the target HbS, which led to reductions in the units transfused. The average per-patient FCR rose from 43.4% before the pandemic to 52.4% during the pandemic in patients with an HbS goal of <30% (p<0.001). Additionally, the mean FCR per patient increased from 48.7 to 54.7% for the <35 to 45% group (p=0.022) and from 54.8 to 60.6% for the <50% group (p=0.013).

While 1,594 units were transfused during a six-month study period, a total of 351 units (18.0%) were saved. The average number of RBC units transfused for each procedure was reduced from 6.1 to 5.0 units (p<0.001). There was a significant correlation between the percentage of units saved for each patient during the pandemic and the patient’s mean FCR increase from their procedures before and during the COVID-19 era (p<0.001).

The percentage increase in FCR for the procedures performed during the COVID-19 pandemic was greater in patients with increased hematocrit compared with patients with unchanged hematocrit (p=0.035), a finding which the researchers suggest is consistent with fewer transfused units per RCE.

While there was an overall reduction in blood use, the HbS target goals prior to transfusion were maintained, while net iron accumulation remained low.

This study is limited by its small sample size. Dr. Chou added that further research should also examine whether other institutions could have similar blood unit savings if the same measures were implemented.

Study authors report no relevant conflicts of interest.


Uter S, An HH, Linder GE, et al. Measures to reduce red cell use in patients with sickle cell disease requiring red cell exchange during a blood shortage. Blood Adv. 2021;5(12):2586-2592.

Over the last several years, there has been a continued decline in RBC supply in the U.S., attributed to an aging donor population and the combination of increasingly stringent donor eligibility criteria and added regulations.1 National efforts such as the Choose Wisely® campaign, the implementation of transfusion guidelines supporting restrictive transfusion practices, and the implementation of patient blood management and conservation strategies have helped to decrease RBC utilization, partially offsetting the decrease in collections.

However, the ongoing COVID-19 pandemic has further reduced the blood supply. In the early phases of the pandemic, donation centers suffered a dramatic decreased in blood collections resulting from the disruption of daily activities of the community, the implementation of stay home directives, and restrictions affecting blood drive operations, such as social distancing and reduced staff availability. This shortage was compensated by lower blood utilization as hospitals prioritized COVID-19 admissions and rescheduled elective surgeries.2 To increase donor pool eligibility, the U.S. Food and Drug Administration updated and shortened donor referral times. More recent blood shortages were associated with a rebound in hospital operations and confusion about donor eligibility associated with COVID-19 vaccines, prompting blood centers to increase donor recruitment and bump hospital collections.3

Variations in blood supply availability are expected to continue. These results invite us to think about the opportunity to conduct well-designed protocol-based clinical studies as an alternative to expensive and operationally challenging randomized clinical trials.

Monica B. Pagano, MD
University of Washington
Seattle, WA


  1. Klein HG, Hrouda JC, Epstein JS. Crisis in the sustainability of the U.S. blood system. N Engl J Med. 2017;377:1485-1488.
  2. Pagano MB, Hess JR, Tsang HC, et al. Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID-19) pandemic affecting Washington State. Transfusion. 2020;60:908-911.
  3. Gniadek TJ, Mallek J, Wright G, et al. Expansion of hospital-based blood collections in the face of COVID-19 associated national blood shortage. Transfusion. 2020;60:1470-1475.