NICE, the National Institute for Clinical Excellence, has just published guidance on the preferred way of undertaking exchange transfusions in sickle cell disease. These recommendations have major implications for all those living with sickle cell in the UK, and will no doubt have an impact on how services are organised, in order to ensure that all patients have access to the most advances treatments. An exchange blood transfusion is an important treatment option in sickle cell and has been in use for many years. It can be used in one off emergency situations but can also be repeated, on a regular basis, to manage some of the long term complications of sickle cell.
The aim of most blood transfusions is to raise the patient’s haemoglobin concentration rapidly because they have become dangerously anaemic. This is sometimes necessary in sickle cell and is then often referred to as a “top-up” transfusion. The purpose of an exchange transfusion however is different; the main requirement is to reduce the number of sickle red cells in the patient’s blood stream, rather than increase the haemoglobin level. The frequency and severity of sickle cell related events are directly related to the amount of sickle haemoglobin in the blood; reduce the number of sickle red cells and the risk of a sickle cell event will also drop in proportion. This is why an exchange transfusion can be potentially lifesaving in something like the acute chest syndrome, by stopping further sickling in the lungs, and also why regular exchange transfusions, repeated every 4-6 weeks, can protect against recurrent attacks of pain, strokes or priapism, prevent deterioration in conditions like pulmonary hypertension (high blood pressure in the lungs) and heal chronic leg ulcers. All good news, but there are some significant problems with exchange transfusions.
In the past “an exchange” was always done manually; blood was removed from the patient using a large cannula and syringe and then replaced with exactly the same volume of blood from a blood donor. This cycle was repeated over and over again until the sickle cell concentration (Hb S%) had fallen to the desired level. In someone with sickle cell anaemia (Hb SS disease), who has not been recently transfused, the Hb S level will be 100%, in other words all the red cells will be sickle red cells. During a manual exchange transfusion the aim was to reduce the Hb S level to about 20%; meaning that only 1/5th of the red cells would be sickle red cells and the rest would be normal, transfused red cells containing haemoglobin (Hb A). In practice, this was often difficult to achieve and would frequently take all day, an exhausting business for the patient and the doctor or nurse doing the exchange.
In addition, as with all blood transfusions there were always concerns about transfusion reactions and the risk of inadvertently immunising the patient against blood group antigens. Both of these risks of increased concern in an exchange because of the large volume of blood which had to be used, often 10 to 12 bags per exchange. When regular manual exchange transfusions were used to manage chronic complications over a period of months or years, there was the added worry of iron overload, or the build up of iron in the body derived from the transfused blood.
The importance of the NICE guidance is that it recommends moving away from manual exchange transfusions and instead making use of technology which can automate the whole process. The automated systems remove blood from the patient, centrifuge, or spin, it to separate red cells from plasma, then mix the patient’s own plasma with donor red cells in the correct proportion before finally returning the re-constituted blood to the patient.
The big advantage of an automated red cell exchange transfusion is that it is quick, taking at the most 2-3 hours rather than a whole day. It is also much more efficient and will routinely bring the Hb S level down to 10% or even less leaving, in other words, only 1 in 10 sickle red cells behind. Since the risk of a sickle cell related event is directly related to the proportion of sickle red cells, the very low levels achieved with an automated transfusion virtually banish sickling completely. In addition, if the patient is on a regular programme, it is only necessary to repeat the procedure every 8-12 weeks rather than every 4-6 weeks, because it takes the sickle red cells a long time to recover from such low levels. Another big plus. Finally, it looks as if the automated exchange is “iron neutral”. In other words the quantity of red cells removed, together with the iron they contain, exactly balances the quantity of red cells and iron returned to the patient, preventing any build up of iron and iron overload. Not only are there many advantages for the patient but NICE also estimates that, using an automated exchange for all sickle patients in the UK on a regular transfusion programme could save the NHS in England £13 million a year.
There are downsides, of course. The machine is expensive, about £45,000 and staff have to be specially trained in it’s use the and the trouble shooting any problems. Then there is the vexed issue of vascular access. A manual exchange uses just one venous line, usually placed in a large vein in the arm. Blood is alternately taken out and put in using the same line. The automated systems need two large, venous lines, one out and the other in, which in practice is often achieved by using a double-barrelled femoral line placed in the large, femoral vein in the groin. Needless to say femoral lines are not popular with patients and insertion requires highly skilled staff. Fortunately, these access problems have to a large extent been overcome as expertise has developed and nowadays many patients have repeated automated exchanges through arm veins, with the two cannulae placed under ultrasound guidance, greatly improving the “hit rate”.
Hopefully, the NICE guidance will prompt a move towards the more widespread use of automated exchange transfusion technology in sickle cell, opening the way for many more patients to benefit from this innovative treatment. NICE has also called for clinicians to work together to define how regular automated red cell exchange transfusions can benefit patients with different sorts of complications. So, expect to see a burst of research activity in the near future which will define the role of this intervention in sickle cell disease more precisely.
Read the guidance from NICE:
Curtis explains the problems:
For background information on blood transfusion: