Clocking the Processes and Challenges of Urgent Red Blood Cell Exchange for Acute Complications of Sickle Cell Disease

Background: Red blood cell exchange transfusion (RBCX) is the therapy of choice for some acute complications of sickle cell disease (SCD), including stroke, severe acute chest syndrome and multi-organ failure. Rapid initiation of RBCX is critical to reduce morbidity and mortality in those with acute complications of SCD. A typical RBCX procedure requires anywhere from 6-10 units of packed red blood cells (RBC) and measures are taken to provide higher-fidelity RBC matches (key RHCE and KEL antigens at a minimum, ±suitable KIDD, FY, Ss profiles for the sensitized). Our recent review of urgent apheresis transfers to our tertiary-care centre, including 26 for RBCX, demonstrated that the median time per transfer was approximately 4 hours. Not yet characterized is the additional time required to start RBCX once a patient arrives. The time required to investigate antibody repertoires, and to procure sufficient quantities of blood that can bypass these specificities, is of interest in a specialty center with substantial but not unlimited investigative expertise and inventory. Methods: This was a retrospective database and chart review of all patients referred to our apheresis service for urgent RBCX for severe complications of SCD between Jan 1, 2013 to Dec 31, 2020. Time stamps for admission, blood bank, and apheresis processes were extracted from the electronic medical record and blood bank database. Categorical variables were analyzed using nonparametric tests. Results: Thirty-eight patients were included (65.8% males, 35.2% females) (Table 1). HbSS was the most common SCD genotype represented (81.6%). Most patients (71.1%) were transferred from another hospital, with the remaining patients arriving through the emergency department (26.3%) and one (2.6%) as a direct admission from clinic. ACS +/- additional complications constituted the most common indication for RBCX (78.9%). Two patients died due to complications of multi-organ failure, the remaining patients were discharged from hospital. Six patients (15.8%) had a positive antibody screen. The majority had RBC phenotype (42.1%) or genotype +/- phenotype (36.8%) on file to facilitate extended matching, and sufficient appropriate units were available in the blood bank in 82% of cases. Four (10.5%) patients required top-up transfusions prior to RBCX due to significant anemia. The median number of units issued per procedure was 9 (IQR 2). The median times from index group and screen (G&S) collection to sample accession, and from accession to result were 23 minutes (IQR 26) and 46 minutes (IQR 31), respectively (Figure 1). The median time from G&S result to RBC units issued was 348.5 minutes (IQR 479). The median total time from patient admission (or determination of RBCX indication) to RBC units issued was 569 minutes (IQR 464). A positive antibody screen, patient origin (ED vs. transfer), and the availability of sufficient RBC units in house were associated with turnaround time from accession of the index G&S sample to the issuing of RBCs (p<0.01 for all). Patients having antibodies to high prevalence antigens (e.g. anti-U) or to multiple targets (demanding unique donor profiles) had some of the longest times to initiate treatment. These constraints necessitated orders and coordinated deliveries of units from across the geographic network of the national blood provider.Discussion: These data from the largest apheresis unit in the country characterize the time invested in blood preparation for an urgent RBCX for acute SCD complications. A positive antibody screen is predictive of increased time to procedure start, reflecting delays inherent to serologic investigations, product sourcing, and serologic crossmatch times. While the precise moment of a blood request was available for a minority of patients, the G&S time stamp was used as a surrogate, thus potentially overestimating turnaround times in the blood bank. Nevertheless, the serologic demands inherent to a case present a tension between speed (treating the disease) and safety (averting immune rejection reactions).