Are You Getting the Right Match?

In the UK, there has been a big increase in the number of patients requiring transplants over the last decade or so. In fact, this pattern can be reflected worldwide. In order to understand why we need more donors to accommodate the continual increase in patients requiring transplantation of solid organs, its useful to know how we determine matches between donors and patients. "Solid" organs as you could infer, relate to organs that are in a solid state. Examples of these include the kidneys, pancreas, heart and lungs. It is widely accepted that it isn't easy to find compatibility between donor and recipient straight away - there must be biological compatibility of two types. The first is the well-known ABO blood group system. There are four different groups that an individual can fall into: A, B, AB, and O. Each group signifies the types of antigen present on the surface an erythrocyte, or red blood cell. Antigens are proteins on the plasma membrane of a cell, giving it its own 'identity'. This is essential in the multiple processes of the immune response, for example. A person identified with an 'A' type blood group has only 'A' type antigens on the cell surface membranes of red blood cells. However they will also have 'Anti-B' antibodies circulating in their blood plasma. The converse is true for those with a 'B' blood group. If someone were to have AB however, they would have both types of antigen on the cell surface membranes of red blood cells. Therefore no antibodies acting against these antigens would be circulating in their blood plasma. Now, those with type 'O' blood group are seen to be rarer than those with other blood groups, but it means as a donor you would be 'compatible' with any recipient of any blood type. For this blood type, no ABO antigens are present on the membranes of red blood cells, but the serum of these individuals will contain the 'Anti-A' and 'Anti-B' antibodies.

Chart showing the differences in cell type, antibodies and antigens present in individuals with different blood groups (Source: Wikipedia )

To illustrate this, let us consider a potential liver transplant between a donor with blood group O and recipient with blood group B. The donor has red blood cells with no ABO antigens, so when mixed with blood (and plasma) containing red blood cells with the B antigen and therefore 'Anti-A' antibodies, there will be no immune response. After all, the antibodies are not able to form an antigen-antibody complex.

Most people will be aware of the ABO blood group system; however there is another factor that always needs to be considered by doctors before carrying out any surgeries involving organ transplantation. This is what is known as the human leucocyte antigen (HLA) system. All cells known to contain nuclei in the body possess these protein complexes on their cell surface membranes. Therefore it is useful to know that red blood cells do not have these antigens as they have no nuclei, no genetic material encased. HLA types are inherited from both parents, and 'research has shown that the fewer the number of mismatches between donor and recipient HLA, the less likely it is that the organ will be rejected post-transplantation'. This is why it has become increasingly imperative for doctors to screen individuals for this type of antigen so that matches between patients and potential donors can be confirmed. A patients HLA type can be confirmed by a series of tests. The polymerase chain reaction (to create multiple copies of DNA) followed by gel electrophoresis (allows the scientist to visualise the result) being one of the more notable methods.

After the HLA type has been confirmed, the patient's serum is analysed to 'screen for the antibody profile'. Firstly, the serum is 'mixed with microbeads that have multiple HLAs on their surface'. This essentially serves to identify antibodies that are targeted at particular donor HLAs, using a fluorescent marker. This is needed as there is always a possibility that the recipient could have developed antibodies against a particular HLA in the past, whether it be pregnancy, previous transplants, or blood transfusions. These are known as 'sensitisation events'.

In addition to this, another test is carried out, involving mixing of recipient serum with donor cells. This is primarily to see if there is any immunological reaction to the donor cells, thus proving whether a donor is in fact compatible with the patient. The donor cells are those with nuclei, so scientists can test whether the HLAs of the donor form an antigen-antibody complex with antigens present in the patient's serum. 'Complement' molecules are also added which help to destroy cells (by lysis) that have their HLA antigens bound to patient antibodies. To see whether a reaction has occurred or not, a visualisation stain is applied, dead cells staining red, and live cells staining green.

Not only is it important to choose the right donor, but selecting viable organs for surgical use is also vital. Donors can either be living or deceased, but living donors 'are generally family members or close friends of the patient'. That isn't to say all are, of course, as altruistic donors are on the rise - these people are willing to donate an organ without knowing who will receive it in due course. Kidney donation is by far the most common transplantation from live donors. In fact, 'in the UK, 2732 out of 3740 transplants performed in 2011 were kidney transplants'. Donations from the deceased however can be divided into two sub-groups: those who are pronounced brain dead (DBD), or those with circulatory death (DCD). DCD is when the heart has completely stopped beating and thus there is no circulation flow throughout the body. DBD donors have organs 'kept alive' by a ventilator, with a constant blood supply in place.

A patient can be found to have their donated organs rejected by their own immune system at several possible stages after surgery:

Hyperacute: Rejection occurs immediately, even within a few minutes of transplantation. Surgeons would need to work quickly to remove the donor organ completely from the body. Nowadays, hyperacute rejection is very rare.

Accelerated acute: Rejection could happen within a few days to a week after surgery. The rejection may be due to the fact the patient has experienced a sensitisation event in the past, which produced the relevant antibodies.

Acute: Rejection occurs within the first 6 months of surgery, and is mainly due to a few mismatches in HLAs between the donor and the patient. This sort of rejection can be brought under control with certain immunosuppresant drugs that are specific to the recipient.

Chronic: Rejection could even occur after 6 months from the point of surgery and mainly due to repeated episodes of acute rejection. This is the main problem facing patients with transplants - some patients will be required to take immunosuppresive drugs for the vast duration of their life.


With a population as ethnically diverse as the UK, it has become increasingly difficult for those of minor ethnic origins to receive the right matches for organ donation, although overall there is a big gap between the numbers requiring transplants and willing donors.Those of Black and Asian origin have been known to have 'uncommon HLA types'. Many countries, such as Spain, Belgium, France and the USA have implemented an 'opt-out' scheme nationwide. This means it is presumed you give consent for your organs to be donated, unless you state otherwise. In the UK, the public's view may be changing on whether we should carry on with our current system in order to meet the piling demand for organs across all ages, all backgrounds, and all ethnicities.


Credit to Steven Jervis, clinical scientist at the Manchester Transplantation Laboratory who wrote for the Biological Sciences Review (Volume 24, Number 1)

"Dead Heart" Transplant - World First in Cardiac Surgery

In Australia this month, surgeons have managed to resuscitate a heart from circulatory death and use it for transplant in patients with 'end-stage heart failure'. Prior to this, hearts used for transplant were only sourced from brain-dead patients but whose hearts were still beating. Some have heralded this as a 'paradigm shift' in organ transplantation. The heart was able to be revived using what has been  dubbed as the 'heart-in-a-box' machine (the OCS - Organ Care System). Now the machine is commercially available to hospitals in Europe and Australia for clinical use. Usually, a beating heart is kept iced for a long period of time, however this machine is claimed to be a 'portable, warm perfusion, monitoring machine'. As of now, St. Vincent's Hospital Heart Lung Transplant Unit in Australia has transplanted two patients using this technique. However it is important to note that the OCS has already been used and approved for other types of transplantation such as the liver, kidneys and lungs. Up until now, it has proved difficult to repeat the same technique on 'dead' hearts.

The benefits of this new technique prove essential - the maximum possible number of donor hearts available will inevitably increase. In fact, it is estimated that 30% more lives could be saved with the introduction of this technique. Professor Peter MacDonald, Medical Director of the St Vincent's Heart Transplant Unit has said "this is a timely breakthrough. In all our years, our biggest hinderance has been the limited availability of donor organs". With regards to the OCS machine, portability is useful if it is needed in various departments in a hospital. It would also mean ease of transportation nationwide, or even worldwide.

 

Top: OCS "Heart-in-a-box" machine (TransMedics)

Above: OCS machine maintaining liver for transplant (BBC)

Interestingly however, this isn't the first time that this idea of using a dead heart donor has been experimented. Professor Kumud Dhital perfumed both of the operations in Austrailia says that "It is interesting to note that DCD hearts were utilised for the first wave of human heart transplants in the 1960's with the donor and recipient in adjacent operating theatres. This co-location of donor and recipient is extremely rare in the current era leading us to rely solely on brain dead donors -- until now".

The recovery of patients is even more astounding. Michelle Gribilas, 57, was the first patient to be treated with the surgery. Before the operation she was suffering from congenital [end-stage] heart failure. Two months after the procedure, she told the BBC: "Now I'm a different person altogether. I feel like I'm 40 years old - I'm very lucky". Senior cardiac nurse at the British Heart Foundation, Maureen Talbot, added "without this development, [patients] may still be waiting for a donor heart".


Credit to the BBC for their article 'Surgeons transplant heart that had stopped beating', published 24th October 2014. More on the subject can be found here.

Credit to St Vincent's Health Australia, whose story was published in ScienceDaily on October 24th 2014. The original article can be found here.

World First In Organ Transplantation

Recently in September, it has been revealed that a woman in Sweden gave birth to a baby boy, only possible with a womb transplantation. This pivotal event in medical science has given hope to thousands of women around the globe who are unable to conceive. Some cancer treatments and birth defects are a couple pf the reasons why women have this problem. The donor of the uterus was a friend of the 36-year old, who was in her 60's at the time of transplantation. The birth was successful, however premature at 36 weeks, the baby weighing in at 1.8kg (3.9lb). Prior to the birth, the unidentified couple underwent IVF treatment in order to produce 11 embryos. These were frozen until the point of transplantation at the University of Gothenburg. As with the vast majority of organ transplants of today, the woman was given immunosuppressant drugs before the transplant, in order to reduce the risk of rejection by her own immune system.

After the transplant, doctors were then able to select an embryo from the ones frozen to implant into the new uterus. However this was only after a period of a year. In the short period before the birth, the baby was said to have developed an abnormal heart beat, hence the premature birth, however now the baby's condition is said to be 'normal'. However complications with this sort of transplant don't just stop there. If the couple were to have a second child, they would need to consider the fact that the immunosuppressant drugs can be 'damaging in the long term'. It would be considered that if they decide not to have a second child, then removing the transplanted womb would be a necessary precaution.

There have been several fails attempts at womb transplants, whether it be due to the organ becoming diseased, or birth resulting in miscarriages. Now, Professor Mats Brannstrom, who led the surgical team expressed relief and happiness in response to the success. In fact it has emerged that two more women will be receiving womb tranplants by the end of this year; suregons in the UK will be choosing 5 patients out of 60 who will undergo this potenially life changing opeation, according to the Sunday Times.

"Our success is based on more than 10 years of intensive animal research and surgical training". Despite the success however there are still concerns about the 'safety and effectiveness of the invasive procure', according to the BBC. This breakthrough is somewhat comparable to the leap in medical science that IVF allowed over 30 years ago. The Chairman of the British Fertility Society, Dr Allan Pacey said the operation "feels like a step change", however he is aware that it will need to be proved repeatable, reliable, and safe in the future for many more patients.


Credit to Oliver Moody, for his article 'More womb transplant babies on the way' which can be found here.
Additional credit to James Gallagher, Health Correspondent for the BBC, for his article 'First womb transplant baby born', which can be accessed here

Organ Transplant Increase Globally

With organ transplantation becoming increasingly in demand, it seems as though steadily the healthcare services of the world are steadily reaching that demand. According to the BBC, 4655 organ transplants were carried out between 2013 and 2014. In fact this is a 10% increase on the interval of the previous year which is interesting to note. But what is more important is that over many years, the numbers have only increased.

This is very encouraging with this rate of progress however many patients are still left over extended periods of time without an organ transplant available.

However how many of us are actually organ donors? The short answer is 20 million registered. The major problem today is the inability for families to give consent of their deceased loved ones to be organ donors after death. The families decision can therefore override the decision made by the loved ones to become organ donors. This could explain the fact that 3 people a day die because organs aren't simply available for transplant, according to NHS Blood and Transplant Data.

I must agree that the decision of the family must be taken into consideration, however it must be the duty of the donor to inform their family of their decision. Ensuring the whole family has made an informed decision is imperative so that their is less risk of organs becoming unavailable 'at the last minute'.

Nevertheless, living donors are equally as important, if not more so. 'Just over 1000' transplants were possible with living donors.

The bottom line question that is asked in this article is "If we would accept an organ for ourselves or would want someone we love to be saved by a transplant shouldn't we be willing to donate one too?".


In fact while we are on the subject, I would like to elaborate on the idea of organ transplantation and consent. In February, I received my quarterly copy of the Biological Sciences Review. I remember there being an interesting column on how consent for organ donation has changed over the past decade or so, with specific insight into the work of the Human Tissue Authority (HTA).

The HTA was set up in 2005, following events where sometimes hospitals 'retained human organs and tissues without consent'. Therefore the subsequent purpose of the HTA was 'to ensure that valid consent is in place for the removal, storage an use of human tissue and organs'. Living matter that was catered for by the HTA ranges from the very small to the large, cells to organ systems.

In 2012, the HTA decided to take on responsibility not just to ensure consent, but ensure that if organs were retained, they would be preserved for their quality. Also making sure the organs were safe for transplantation.

Another important duty of the HTA is to regulates the actions of 'all organisations that remove, store and use tissues and organs for research, medical truing, post-mortem examination, education and training, and display in public'.

In addition to handing organs and tissues from dead donors, the HTA also has responsibility for the viability of all organs and bone marrow tissue from living donors.

I really like the idea of having a HTA as it reassures the public of the safety and viability of organs when organ transplantation is needed. It acts like a 'watchdog' by inspecting organisations that store, remove and use human tissue. By licensing these organisations, hospitals, and the public will know of the quality of the organs that will be used for transplantation.

Another positive aspect I feel that will emerge from this is increased confidence in organ donation. The HTA 'hopes more people will donate their tissues for scientific and medical research…for transplants…fore medical education and training.'

What astonishes me the most is that according to this article, in the year 2011-2012, 'the HTA approved 1214 living organ donations…the vast majority (96%) were kidneys'. It seems that kidney transplantation, living kidney transplantation is very much in demand. Only the remainder were donated liver lobes.

But who receives the donation? In fact 9 out of 10 donations were for the family members. Converesly there were 39 "altruistic" donations, were the donor wishes there organ to be directed to the patient in the hospital with the most clinical need.

In truth, I have endless appreciation for the donors that give up part of their own body, to help others, sometimes others that they even don't know. No knowledge of family history, personality, causes of the health issue…nothing. It is the ultimate selfless act.


Credit to Alan Clamp, current Chief Executive of the HTA, who wrote for the Biological Sciences Review (Volume 26, Number 3)

Additional credit to Nick Triggle of the BBC whose article can be found here