The transfusion of blood, or more correctly of red cells, is a frequently used intervention in sickle cell disease, either as a lifesaving or a disease modifying treatment. As many as 90% of adults with sickle cell will receive a blood transfusion at least once in their lives. Although transfusion is a common and straight forward procedure there can be problems and difficulties; this blog attempts to give you some background information about those problems, and indicate how you can take an active part in keeping them to a minimum.
In the UK blood for transfusion is collected from volunteer donors.
Red blood cells for transfusion have a limited shelf life; if stored at 4 degrees centigrade they remain viable for only 35 days. Stocks of blood therefore have to be constantly replenished.
Approximately 8,000 blood transfusions are given every day in the UK, meaning that the collection, testing and transport of blood around the country is a major undertaking.
Blood transfusions in sickle cell disease may be given as a simple “top-up” transfusion or as an exchange transfusion. A “top up” transfusion is when blood is given to correct a low haemoglobin level. A drop in haemoglobin to below your normal steady state value can occur in a variety of situations, for example a painful crisis complicated by an infection or an aplastic or sequestration crisis. An exchange transfusion is when blood is removed as well as given and the aim is both to raise the haemoglobin level and to reduce the proportion of sickle haemoglobin in the blood. This might be used acutely to stop the sickling process, such as during an acute chest crisis or the exchange transfusions may be given on a regular basis to suppress the activity of the disease.
The actual process of blood transfusion is straight forward; the blood is given via an intravenous cannula, whilst the nursing staff carry out regular measurements of pulse, blood pressure and temperature. These measurements are taken because they give an early warning signal of impending problems.
One of the main reasons patients worry about blood transfusion is that they fear they might become infected by a virus transmitted by the transfusion. In practice this is a very rare occurrence and should not be a major concern. Before donating the volunteers read a questionnaire, which is designed to eliminate those donors who have a high risk of transmitting blood borne viruses, such as the hepatitis viruses and HIV. After the blood has been collected it is then exhaustively tested for the presence of these viruses, and only if it is completely negative is it released for transfusion. As a result of these precautions the risk of acquiring a viral infection from a blood transfusion in the UK is very small indeed. The latest figures show that in the UK, over a period of 16 years from 1996 to 2012, only 13 patients acquired hepatitis B infection, 4 HIV and 2 hepatitis C by blood transfusion. This gives a risk of <1 in 1.2 million donations for hepatitis B infection, <1 in 7 million donations for HIV and <1 in 28 million donations for hepatitis C. These risks are very, very small and should not worry you. It is important to remember however, that in many countries around the world, because viral infections such as these are more common and because the testing procedures are less stringent than in the UK, the risks of viral transmission by blood transfusion are much higher.
As well as testing for viruses, before transfusion the donated blood is also “grouped”. There are 4 main “ABO” blood groups; group O and group A are the commonest, followed by group B and group AB. Whatever the ABO group the blood will also be either Rhesus (Rh) D positive or negative, often abbreviated as just “pos or neg”. Generally speaking you will usually be given a blood transfusion with blood of the same ABO and Rh D group as yourself. So, for example, if you are group A Rh D positive then you will generally be given blood which is also group A Rh D positive. There are some exceptions to this, for example group O Rh D negative blood can be safely given to patients with any ABO and Rh D group.
The “transfusion process” is a term used to describe the complex sequence of events from when blood is first selected for a patient from the blood fridge in the laboratory to when it is actually transfused on the ward. Mistakes in the transfusion process, which are usually caused by human error, are the commonest cause of problems with a blood transfusion. The most dangerous error is when patients are given blood of the wrong ABO group, this can lead to an immediate, or acute, transfusion reaction, which can be life threatening. The patient receiving the blood becomes very unwell during the transfusion, they may go on to develop kidney failure, and they may require intensive care or even die as a consequence. This is also, fortunately, a very rare occurrence: SHOT (Serious Hazards of Blood Transfusion – a confidential enquiry into all serious transfusion problems) reported that in 2013 there were only 9 ABO incompatible red cell transfusions in the UK, although in one of these cases the transfusion may have been contributory to the patient’s death.
There are multiple checking steps in the transfusion process to try to eliminate this possibility, including the nurses on the ward, who will check the blood you are given at least twice before the transfusion. You, the patient, have a very important role in this process by making a point of knowing your own ABO and Rhesus D group and stopping the nurse if they attempt to give you blood of a different blood group. Remember, sometimes this will be OK and in that case the nurse will reassure you, or alternatively check with the blood transfusion laboratory to make sure that it is safe to proceed. Do not be reluctant to challenge the nurse if you think you are not being given the right blood.
Having a blood transfusion is a bit like having a transplant. Because you are given blood from a genetically different person your immune system may react by producing antibodies to the “foreign” chemicals on the surface of the red blood cells you receive. This process is called alloimmunisation. About 2.5% of non-sickle cell patients will develop alloantibodies after a blood transfusion, but among sickle cell patients the rates can be much higher, often 20% or more. Why is this?
Well partly it is due to the frequency with which patients with sickle cell disease are transfused and the number of different blood donors they are exposed to. The greater the exposure the more likely you are to become immunised and make antibodies. But there are also other factors at work here. The pattern and frequency of the different antigens on the surface of red blood cells varies between people but also varies between different ethnic groups. For example, the Duffy antigens are completely absent in nearly three quarters of black people of African origin whereas they are almost always present in white caucasians. Now the vast majority of blood donors in the UK are white caucasians, which means that sickle cell patients are more often exposed to red cell antigens common in the white caucasian, blood donor population, increasing their risk of alloimmunisation. To a certain extent we avoid this by typing blood for transfusion to sickle cell patients in more detail to try and avoid these mismatches, but it is also important to try and increase the number of blood donors from different ethnic groups. This is where you can help – why not speak to your family and friends and encourage them to become regular blood donors (http://www.blood.co.uk/) – it’s easy!
What are the consequences of alloimmunisation? Well firstly, it can make finding compatible blood in the future more difficult, because you have to make sure the blood will not react with the antibodies that the patient has. Secondly, at the time of a transfusion, it can lead to a delayed transfusion reaction. These are reactions which can happen many days after a transfusion and, just like immediate reactions to ABO incompatible blood, the reactions vary in severity but can be very serious. Kings College Hospital, in south London, has just reviewed all the delayed transfusion reactions in their large population of patients with sickle cell disease over a period of 5 years. They found that these reactions were rare, occurring in only 1.1% of the transfusions they carried out. But they also found they were more common when transfusions were given when patients were ill (3.4% of transfusion episodes) rather than as part of an ongoing, chronic transfusion programme (0.2% of transfusion episodes). It is as if during a crisis a patient’s immune system is on high alert and sensitised in some way to react to foreign antigens.
How does a delayed transfusion reaction affect the patient? They usually re-presented some 7-21 days after the transfusion with what at first sight appeared to be a particularly severe painful crisis, but they also had a temperature, their urine was red due to the presence of haemoglobin and they had often become very anaemic. The patient’s own immune system had destroyed the transfused red cells, the haemoglobin from the red cells was lost in the urine and the whole process provoked a bad painful crisis. The majority of episodes were classed as “moderately severe” and the patient required further blood transfusions to correct their severe anaemia, but in a small number of cases the reaction was very severe, requiring intensive care, multiple blood transfusions and a variety of different treatments to try and halt the haemolytic reaction.
Do you have any red cell antibodies? Again the thing to do is to ask your doctor; if you do have antibodies you should be issued with a card by NHS Blood & Transplant detailing what type of antibodies you have, which you should carry with you. Whenever you have a blood transfusion check with the nurse looking after you that the blood you are being given has been screened and is negative for the antigens you react against.
The final issue with blood transfusion that patients worry about is the accumulation of iron. Iron is an essential part of the haemoglobin molecule and every bag of blood contains about 250mg of iron. We don’t have any natural way of getting rid of excess iron so in people who have multiple blood transfusions the level of iron in the body gradually builds up. This doesn’t really begin to become a problem until you have received more than 20-30 units of blood so only really applies to patients with sickle cell who are on a long term blood transfusion programme. Assessing and managing iron overload is a big topic and I will try and explain what you need to know about this in the next blog.
Delayed haemolytic transfusion reaction in adults with sickle cell disease: a five year experience. Vidler JB, Gardner K, Amenyah K, et al. British Journal of Haematology, 2015, volume 169, page 746-753