Sickle cell disease is an inherited genetic disease affecting red blood cells. The cells are a crescent – or sickle – shape instead of the normal round disc shape, affecting the cell’s ability to carry oxygen and move around the body. Symptoms may include intense pain and severe anaemia, and the condition can cause damage to major organs, infections and life-threatening complications.
Sickle cell disease is the commonest inherited monogenic disorder in the UK, where there are between 12,500–15,000 people affected, with an estimated 240,000 genetic carriers. It is more prevalent among people of African and African-Caribbean descent, but it can affect other ethnic groups too.
Disease-modifying approaches are limited currently and these consist of Hydrea® (hydroxyurea or hydroxycarbamide), blood transfusions (top up, manual and automated red blood cell exchanges (RBCX)) and stem cell transplantation. The latter is not the most suitable approach for many of these patients.
The majority of patients with SCD who are on long-term transfusion regimens will nowadays have regular automated red cell exchanges. The most frequent indications are primary or secondary stroke prevention and recurrent sickle pains or chest syndromes that do not respond to hydroxycarbamide. It might be considered a reasonable approach – although evidence is lacking – for patients with progressive sickle-related liver or renal disease.
Frequency and target parameters (target pre- and post-RBCX Hb and HbS) are decided by the sickle team looking after the patients and varies from patient to patient, but generally the aim for stroke prevention is to keep the HbS percentage well suppressed at <30% prior to each exchange and the usual frequency is six-weekly although some patients might need them more frequently to maintain optimal HbS control.
Emergency automated exchange transfusions may sometimes be needed for the management of patients presenting acutely unwell, mainly for these presenting with acute chest syndrome or stroke, fulminant priapism or other life-threatening complication, that is, multi-organ failure.
Elective exchange transfusions may also be required prior to major surgery and during complicated pregnancies.
Generally, exchange transfusions can be performed manually or can be automated using a cell separator. Both approaches are suitable for inpatients with acute sickle complications requiring emergency red cell exchange and for outpatients on an elective red cell exchange programme.
The proportion of blood exchanged can be varied with either approach as can the intended target final Hb and both approaches can be performed isovolaemically, provided that venous access is adequate.
The advantages and disadvantages of manual and automated RBCX transfusions are listed below:
- Is relatively quick: it takes approximately two hours to achieve a target HbS of <30% in patients with good venous access, using a single continuous flow procedure.
- Can be programmed to achieve a target final Hb, %HbS and net fluid balance. If the goal is to achieve the lowest proportion of HbS containing cells as fast as possible this approach will be the quickest where available.
- When more than 30–50% of the total blood volume is exchanged, care must be taken to avoid acute hypocalcaemia and dilutional thrombocytopenia.
- Use is limited in many parts of the UK by the unavailability of cell separators and/or trained operators. However, this is being addressed.
- Requires less equipment and can be performed in any ward or day care setting without the need for a cell separator or trained cell separator operator but takes longer than automated.
- Can be performed with a single vein, or with an indwelling line (although it is done most quickly and isovolaemically using a two-arm technique).
- This approach is effective on an outpatient basis for maintaining HbS <30% but has to be performed every four weeks ( as opposed to an average of six-weekly with the automated RBCX).
- Rapid reversal of chest syndrome can also be achieved effectively with a partial exchange.
- Protocols differ from hospital to hospital and will need to be agreed with the SCD specialist centre.
- The NICE guidance states that manual red blood cell exchange is not iron neutral.
Spectra Optia Apheresis System
The recent NICE medical technology guidance supports the use of the Spectra Optia Apheresis System for automated red blood cell exchange in patients with sickle cell disease who need regular transfusion.2 The device automatically replaces sickle red blood cells with healthy red blood cells in people with the disease. The Spectra Optia is faster to use and patients need the process less often than manual red blood cell exchange.
The NICE guidance suggests that based on current evidence and expert advice on the anticipated benefits of automated red cell exchanges via Spectra Optia when used in patients with iron overload, usage of Spectra Optia for the automated exchanges is cost-saving compared with manual red blood cell exchange or topup transfusion. The savings depend on the iron overload status of the patient, and are more likely to be achieved if devices already owned by the NHS can be used to treat sickle cell disease.
In our centre all our patients receiving regular elective exchanges, are on the automated red cell exchange programme. We have been using the Spectra Optia for over five years now. The procedure time is 2–3 hours on average and we conduct over 900 automated red cell exchange transfusions in sickle cell patients per year. This is a nurse-led service.
Automated RBCX on average necessitates 10 units of packed red blood cells every six weeks in an adult sickle cell patient and the fact that the Rh types of donors differ from the patients’ (due to different ethnicity mainly) makes it difficult to use the limited resource appropriately. In addition, some patients are not able to have regular RBCX due to the difficulty in finding sufficient numbers of antigen negative blood units. Also it is unknown whether those regularly transfused are more at risk of emerging pathogens.
Hence it would be in the patient’s best interest if the same clinical effect could be achieved with less blood use. It was already known that patients undergoing manual exchanges would often, in effect, have a red cell depletion at the beginning of an exchange, with the first unit of blood in being exchanged with normal saline. The technology of the Spectra Optia permits a similar technique where at the outset of the exchange, donor blood does not enter the circuit.
At our centre, data were collected over 12 months from the apheresis database and of 125 patients, 70 patients received depletion exchanges. Depletion efficacy was evaluated on 454 monthly depletion episodes in these 70 patients.1
The outcome of this study showed that red cell depletion is a safe method of reducing blood usage whilst maintaining efficacy in automated RBCX and a patient who would be on 6% depletion every six weeks would on average use seven units less per year.
Securing adequate vascular access is essential for a successful apheresis procedure, especially for an automated one. In most, peripheral access is preferred but it is not always technically possible. Ultrasound-guided peripheral vascular access (USG-PIVA) is a well-documented technique in the setting of emergency departments. However, limited data exists reporting its use in the context of automated red cell exchanges (a-RCEx).
In our centre, between April 2014 and July 2015, 84 USG-PIVA procedures were performed on 38 patients and 71 USG-PIVA (85%) were successful, 13 (15%) were unsuccessful. Veins were successfully cannulated in the upper arm: basilic (22), brachial (33) and cephalic (2) veins; in the antecubital fossa: basilic (3) and median cubital (7); in the lower arm: cephalic (2) and radial (2).
The cannulas we used were the Introcan Safety® Braun 22G (1), 20G (9) and 18G (61). Inlet flow rates achieved: 30–60ml/min (mean 45ml/min). Depth of veins cannulated: 2–12mm (mean 5mm). Two complications were observed – one cannula displacement and one nerve injury. No arterial punctures occurred. Central venous catheters were avoided in 49 patients.
The US-PIVA method offers an effective alternative to central venous access in patients requiring a-RCEx procedures who lack visual or palpable peripheral access, with minimal complications seen in this series.
Summary of NICE guidance
As the life expectancy of sickle cell patients is increasing, the need for treatment of sickle related complications will be increasing. Automated red cell exchange transfusions are faster to use, need to be done less often than manual red blood cell exchanges and the risk of iron overload would potentially be less.
Spectra Optia should be considered for automated red blood cell exchange in patients with sickle cell disease who need regular transfusion.
NICE recommends collaborative data collection to generate further clinical evidence on some outcomes of treatment with Spectra Optia. In particular, there is a need for longterm data on how automated and manual exchanges affect iron overload status and the subsequent need for chelation therapy.
Based on current evidence and expert advice on the projected benefits of the technology when used in patients with iron overload, cost modelling shows that in most cases using Spectra Optia is cost-saving compared with manual red blood cell exchange or topup transfusion. The savings depend on the iron overload status of the patient, and are more likely to be achieved if devices already owned by the hospital can be used to treat sickle cell disease.
- Trompeter S et al. Red cell depletion in automated red cell exchange: a safe and effective method of exchange transfusion whilst reducing blood usage. Br J Haematol 2015;169:91–2.
- NICE. Spectra Optia Apheresis System for automated red blood cell exchange in patients with sickle cell disease: Scope. London: National Institute for Health and Care Excellence; 2015.