14. Transplantation and Rejection Flashcards
What is transfusion?
The transfer of blood or blood products from donor to recipient
What is transplantation?
The transfer of organs/tissues/cells from donor to recipient
What does NHS blood and transplant do?
- Manages blood transfusion and transplantation services
- includes donation, storage and transplantation of blood/blood components, organs, tissues, bone marrow and stem cells
- research
- 1.6 million units of blood a year
Why is there a push to increase black and ethnic minority donors?
- they are more likely to have certain blood types like Rh0 or B+
- This is very important for sickle cell patients
- important for people who need to have regular transfusions as they need to have an almost perfect match.
Who can receive a blood transfusion?
- potentially anyone
- people with severe blood loss through trauma
- neonates
- Pregnancy
- Surgical patients
- chronic anaemia
- cancer patients
Who can be a transfusion donor and what can they donate?
- potentially anyone
- Whole blood products
- Apheresis to separate blood products into platelets, plasma, granulocytes, concentrated RBC
- Stem Cells
What health checks do donors have to go through?
- All done to check out the infection risk
- Travel, Tattoos, recent infections, chronic conditions
- Screening for infections
What microbiological screening does blood go through?
Mandatory: HIV, HBV, HVC, HTLV, HEV and syphilis
Discretionary: Malaria, WNV, CMV, extra HBV (done if donor health checks bought up questions )
Bacterial screening: done for platelets only as they are stored at room temp so have a better chance of developing bacterial growth
What is a transfusion transmitted infection?
- An agent present in the bloodstream in an infectious form at a sufficient dose for infectivity.
- AND can withstand storage conditions for the blood products prior to transfusion
- viruses, bacteria and parasites but not all infectious agents
What are the bloodgroup antigens?
- A+/-
- B+/-
- AB+/-
- O+/-
Why do we need to consider blood group when doing a transfusion?
- The antigen on the surface of RBC can elicit an immune response
- There are 36 blood groups but we mainly worry about the main 8
- Alloantibodies form in response to antigens not present on the persons own RBC
- clinically significant alloantibodies cause problems in transfusion and transplantation
- We always consider donor and recipient ABO and RhD blood group
- Extended blood grouping is needed for people that need regular transfusions like sickle cell patients
Where are ABO antigens expressed?
- Red blood cells
- endothelial cells
- Epithelial cells
When do ABO antibodies arise?
most people have the naturally and are important for transfusion and transplants
When do anti-RhD antibodies arise?
AFTER exposure to incompatible blood including in pregnancy.
RhD incompatibility can cause immediate haemolytic transfusion reactions
Why do ABO alloantibodies arise naturally?
due to parts of the gut microbiome expressiing very similary carbohydrate antigens
When was the 1st organ transplant?
1905 - a cornea
When was the 1st liver transplant?
1963
When was the 1st kidney transplant?
1954
When was the 1st heart/lung transplant?
1983
In the UK how many people die in circumstances where transplantation available?
~5000
How many people die every day due to the shortage of donor?
3
What tissues/organs can be transplanted?
- Heart
- Kidney
- Liver
- Lungs
- cornea
- Heart valves
- bone
- skin
- hand
- face
- uterus
- small bowel
What cells can be transplanted?
- haemopoietic stem cells for leukaemia
- pancreatic islets
- other stem cell populations
Why would you need a transplant? - kidneys
chronic kidney disease leading to end stage renal failure
caused by
- diabetes
- nephritis
- polycystic kidney disease
Why would you need a transplant? - heart
- congenital heart disease
- coronary artery disease
- heart failure
- cardiomyopathy
- Valvular heart disease
Why would you need a transplant? - lungs
- Cystic fibrosis
- pulmonary oedema
- emphysema
- pulmonary hypertension
Why would you need a transplant? - liver
end-stage liver failure caused by:
1. congenital liver defects
2. chronic liver disease - cirrhosis and fibrosis
Why would you need a transplant? - blood
Cancers
1. leukaemia
2. lymphoma
3. myeloma
Immune system/ metabolic disorders
1. sickle cell anaemia
2. thalassaemia
3. severe combined immunodeficiency
Why were the 1943 Gibson and Medawar skin graft experiments important?
- important to understand the role of the immune system in transplant rejection.
- including donor-specific response, systemic immunity, immunological memory
Why is the immune system a major barrier to successful transplantation?
- HLA class 1 are on all nucleated cells so can affect any transplant
- lymphocyte recognition of mismatched HLA is a major cause of rejection
- HLA genes are highly polymorphic so exact matching is very hard
What are autologous transplants?
transplant from one part of the body to another part within the same person
What are syngeneic transplants?
transplants between genetically identical people like identical twins
What are allogeneic transplants?
Transplants between non-identical people of the same species
What are Xenogeneic transplants?
Transplants between animals of different species.
This has the biggest risk of rejection.
Why is HLA-matching important?
- in an ideal world every transplant will be a 100% match, not it is not possible
- HLA-matching is essential for haematopoietic stem cell transplants to avoid graft versus host disease
- HLA-matching is carefully considered for kidney transplants as they have more time to match them up due to dialysis and the length of storage of kidneys
When is HLA-matching not considered?
- For heart and liver transplants
- organ preservation is a lot harder
- recipients are often critically ill
- ABO and anatomical matching is considered
- immunosuppression overcomes HLA mismatches
HLA matching: tissue typing
PCR/NGS and serological techniques to determine HLA compatibility
HLA matching: cross-matching
tests performed for anti-HLA alloantibodies in the recipient.
Called the complement-dependent cytotoxicity test
HLA matching: other tests
- Serum from recipient screened pre-transplant
- Serum screened post-transplant to help detect rejection
Why is it important to encourage black and minority ethnic donors?
- organ donation rates are a lot lower due to cultural differences, lack of trust, religion
- most minority ethnic patients wait longer for a transplant
- it is important to have a large pool of ethnically diverse donors
Why is immunosuppression important in transplantation?
- developed in the 1960s
- allowed for non-HLA-identical transplants like heart
- cyclosporin inhibits proliferation and differentiation of T cells
- before cyclosporin most hearts and livers were rejected
- downsides of every drug like kidney damage
what is a draw back of long-term immunosuppression?
- vulnerable to infection
- increase the risk of cancer
What is a possible future of transplantation?
using enzymes to remove blood group antigens to get over the matching problem
What needs to be considered for organ donation?
- type of donor - living or deceased
- consent for donation
- how the organs/cells are obtained
- how the organs/cells are processed
- how the organs/cells transported and stored
- degenerative biochemical changes
What are some of the problems with living donors?
- lack of organ availability leading to donation for financial gain
- black market organs that are very dangerous for both donor and recipient
What can you donate while you are living?
- bone marrow
- 1 kidney
- lobe of the liver
What are the 2 types of deceased donors?
- donation after brainstem death (DBD)
- Donation after circulatory death (DCD)
What is the criteria for brainstem death?
- catastrophic brain injury
- on a mechanical ventilator without which they wouldn’t survive
- 2 doctors must agree
- highly regulated
- Hard for families as they can still look alive
What is uncontrolled circulatory death?
organ retrieval happens after unexpected cardiac arrest and the patient can’t/shouldn’t be resuscitated
What is controlled circulatory death?
organ retrieval happens after a planned withdrawal of life-sustaining treatment
How many organs can you get from each donor?
DCD = 2.8 organs
DBD = 3.2 organs
Why is there lower donation potential for DCD donors?
- Ischaemic injury can occur in solid organs in the time between treatment withdrawal and cold perfusion
- the liver and pancreas are vulnerable but it is very problematic for heart transplants
- BUT DCD donors may be better for lung transplants to avoid a sympathetic storm
What is a sympathetic storm?
An acute response of the sympathetic nervous system and produces lots of adrenaline.
Can dramatically affect the lungs
What is a big barrier to donor consent and organ donation?
- families not talking about what they want to refusing donation on behalf of someone that wanted to donate
- living donors cannot financially benefit at all
What is considered with donor status?
- cause of death
- age
- Co-morbidities
- smoker status
- active malignancy
- graft quality
- ischaemic time
What is warm ischaemia?
When the donor organ is still in the body but cut off from the blood flow.
AND
When the organ is reattached in the recipient but blood flow hasn’t been restored
What is cold ischaemia?
when the organ is in cold perfusion after retrieval
What is reperfusion injury?
Reoxygenation causes dysregulated cellular metabolism which leads to a build up of ROS and cell injury
What happens in organ processing and transport?
- need to prevent tissue deterioration and contamination
- organs must be retrieved immediately from decreased donors
- Organ retrieval service is 24/7
- degenerative change can occur during transport
What causes degenerative changes during organs transport?
- enzymes
- oxidation
- free radicals
- microbial growth
How can we limit degenerative changes?
- freezing of non-living tissue (-40–80) bone, cartilage
- cryopreservation of living tissue (-135) heart valves, arteries, skin
- storage of living tissue above 0 to support cell metabolism, proliferation, protein synthesis and cell repair
- Hypothermic storage (0-4) reduces metabolism and bacterial growth and increases tolerance to ischemia
How long can organs last in hypothermic conditions?
- kidneys <2 days
- liver <24 hours
- Heart <6 hours
- Cartilage <28 days
What is normothermic perfusion?
- deliver oxygen and nutrients
- removes waste products
- maintains blood vessels
- viability testing
- but it is complex and costly
What microbiological screening do organ donors undergo?
- done to avoid donor-derived infection
- similar to transfusion tests
- additional CMV and EBV tests
- the majority of the adult population are infected with CMV and EBV
Mandatory: HIV, HBV, HCV
Recommended: HTLV, HEV, syphilis, CMV, EBV,
How is organ offering done?
- which patient needs organs most urgently
- which patient is most likely to benefit
- A computer program matches patients to organs with agreed prioritisation
- decisions vary by organ type but considerations include: blood type, clinically significant antibodies, tissue type, geography, likelihood of being offered another organ, time on transplant list
What are some surgical complications of transplants?
- infection
- rejection
- immunosuppression
- non-function of transplanted organ
- recurrence of disease
6, quality of life
What is the future of transplantation?
regenerative medicine
1. regenerate and repair damaged tissue
2. stem cells
3. gene editing
4. 3D printing
5. need graft vascularisation and innervation
