Automated red cell exchange: a simplified formula for how many red cell units to exchange and validity of haemoglobin S levels measured one to two hours later.

Dear Sir, Red cell exchange (RCE) remains an effective therapy for the acute complications of sickle cell disease1. Modern apheresis machines have built-in formulae or web-based tools for determining how many red cell units to use for RCE and precise formulae have been presented for calculating the red cell volume to be exchanged2. We present a simpler calculation and show that the use of our method leads to effective RCE. Although the most often quoted goal of reducing haemoglobin S (HbS) levels by RCE in patients with sickle cell anaemia or its variants is to 30% or under, it has been noted that it is not necessary to maintain HbS at such levels. Cohen et al.3 found that a target HbS level of 50% afforded a high rate of protection, even in stroke prevention, while reducing blood requirements by 33% to 99% and thereby lessening the rate of iron accumulation3. Limiting the number of red cell units used also decreases the likelihood of infectious diseases and the risk of alloimmunisation to blood cell antigens from exposure to more donor blood products. However, the goal of RCE is variable, depending on the clinical circumstances; for example, for limb surgery in which a tourniquet is applied, the goal would be a significantly lower HbS level for protection under ischaemic conditions and our formula is not applicable in this kind of scenario. Also, for chronic RCE (e.g., for stroke prophylaxis), the formula is likely to overestimate the amount of blood needed and we readjust the number of units exchanged based on how often the patient returns for RCE in order to keep the HbS level under 50% before the next visit. Under an Institutional Review Board (IRB)-approved protocol, we studied 68 patients diagnosed with sickle cell disease or sickling variants (e.g., HbS-beta thalassemia, HbSC) with initial HbS levels above 50% (average 78.7%) who underwent automated RCE with the COBE® Spectra System (CaridianBCT, Lakewood, CO, USA). Our goal was a post-RCE HbS level of 30–35%. Red cells exchanged were compatible, leucodepleted, and HbS-negative, with the additive solution removed after centrifugation. The machine can determine the replacement volume following input from the operator, who programmes the patient’s gender, height, weight, blood volume, starting and ending haematocrit, haematocrit of replacement fluid, fluid balance, and the percentage (fraction) of cells remaining (FCR). We used a much simpler calculation for patients whose indications included predominantly acute chest syndrome (n =46), urgent surgery (n =8), stroke and cerebral ischaemic events (n =6), allowing us to determine how many red cell units to exchange, thus enabling the Transfusion Service to prepare the appropriate number of red cell units needed as soon as possible. This minimises delay and avoids the preparation of more blood units than actually needed, thereby reducing costs and the potential for wastage of red cells. Our calculation, based on observations of RCE over a number of years and taking into account pre- and post-RCE HbS levels and improvement in the patient’s clinical condition, is as follows: ten percent of a patient’s body weight in kilograms multiplied by the patient’s HbS level (if known, if not assume 100%), and, if the resulting decimal is 0.5 or more, round up to the next full unit. The scientific validity of this approach is supported by the following considerations: (i) it is assumed that one blood volume of an average adult is 70 mL/kg and that the haematocrit is 30%; (ii) the blood volume in a 70 kg patient will then be estimated to be 4,900 mL and the red cell mass 1,470 mL; (iii) if the volume of a unit of packed red cells containing additive solution and reduced plasma, white cells, and platelets is 330 mL with an approximate haematocrit of 60%, then its red cell content is roughly 200 mL; (iv) it will, therefore, take approximately seven red cell units to replace the red cell mass in the 70 kg patient (1,470 mL ÷ 200 mL); (v) accordingly, the number of red cell units (n =7) needed for a one-volume RCE is approximately 10% of the patient’s weight in kg (in this case, 70 kg). A 70 kg patient with a HbS of 100% would be exchanged with 7 red cell units; a 70 kg patient with a HbS of 80% would be exchanged with 7×0.8=5.6, or 6 units. Pre- and post-HbS levels are used to document the efficacy of the RCE. Unless the patient requires a higher haematocrit for surgery or other indications, we ordinarily set the machine for a post-RCE haematocrit close to that of the patient’s baseline level or slightly higher. Since 63 of our patients had starting haematocrit values lower than 30% (average 21.5%), we would have expected the resulting HbS levels to be under 30%. The average was 27.8% (see below). Retrospective review of 68 patients who had RCE performed with calculations employing the “10% rule” showed that all of them tolerated the procedure well and achieved the desired clinical benefit. Pre-RCE HbS values ranged from 51.4% to 97.4%. The average post-RCE HbS level was 28.6% (range, 16.1–42.1%). Post-RCE HbS levels were under 40.0% in 98.5% of cases (which included all patients except one who had a post-RCE HbS level of 42.1%) and ≤35% in 81% of patients. A t test used to compare post-RCE HbS levels in patients with starting haematocrit values ≥30% (mean ± SD, 34.9±6.1%, n =5) with those in patients with starting haematocrit values <30% (mean ± SD, 27.8±6.3%, n =63) showed a statistically significant difference (P =0.018). Both results were within the clinically effective range. We also compared the number of red cell units needed for a goal 30% post-transfusion HbS level predicted by the COBE® Spectra with the number predicted by our “10% rule”. Complete data were available for 61 patients. The COBE® predictions exceeded the “10% rule” by 1.4 units per patient (mean ± SD by paired t test): COBE® 6.62±2.71 versus 10% rule: 5.21±2.37, P <0.0001). In addition, because it is beneficial to know the results of RCE as soon as possible, we studied post-RCE HbS levels at two time points (1–2 hours and 6–8 hours) in a separate IRB-approved study in 11 RCE episodes (10 adults and one child, aged 10 years, weighing 32 kg, with an initial HbS level of 83.8%, who was not part of our IRB-approved study, but who had samples drawn at the clinician’s initiative). Adults ranged in age from 18 to 57 years, weighed between 48 kg and 99 kg, and their initial HbS levels ranged from 46.1% to 85.4%. Samples were drawn during or within 45 minutes of the prescribed intervals in all except one case in which the second time point was at 10 hours (instead of 8 hours). Post-RCE HbS levels at the first time point ranged from 23.2% to 32.7%, and at the second time point from 23.9% to 34.8%. The end-point was improvement in clinical symptoms in all patients. A paired t test comparing HbS levels in the 11 patients at the first time point post-RCE with those at 6 to 8 hours (10 hours in one case) showed a small increase in HbS (mean ± SEM; 31.41±1.53 at the first time point, as compared with 32.45±1.64 at the second time point; 1.0% increase; P =0.0013); although this small increase was statistically significant, it is not likely to be clinically relevant. The other haemoglobin fractions (A, F, A2) showed no statistically significant changes during these intervals. In summary, we present a simplified method for determining the number of red cell units to use for clinically effective RCE and suggest that this method can facilitate timely exchanges and, perhaps on average, enable the use of fewer red cell units. In addition, although studied in few patients, we present data indicating that a sample for HbS evaluation drawn 1 to 2 hours after RCE results in as clinically meaningful an assessment of the efficacy of RCE as a sample drawn at 6 to 8 hours. These observations make possible an earlier decision regarding repeat RCE, if necessary, or removal of the access catheter if it is no longer needed. The results confirm that, after RCE, as with transfusion in anaemic patients4, haemoglobin and haematocrit levels equilibrate more rapidly than has been realised in the past5.