Transplantation

Question 1

What is the difference between life-saving and life-enhancing transplantation?

Answer 1

Life-saving – other life-supportive methods are not fully developed or other life-supportive methods have reached the end of their possible use
Life-enhancing – other life-supportive methods are less good e.g. Kidneys and dialysis – the organ is not vital but it improves the quality of life

Question 2

What are the different types of transplants?

Answer 2

Autograft – within the same individual
Isografts – between genetically identical individuals of the same species
Allograft – between different individuals of the same species
Xenograft – between individuals of different species
Prothetic graft – artificial material e.g. plastic, metal

Question 3

Give an example of an autograft.

Answer 3

Coronary artery bypass graft

Question 4

What tissues can xenografts be used for?

Answer 4

Heart valves

Skin

Question 5

What are the two types of deceased donor?

Answer 5

Donor after brain death – brain dead but heart-beating

Donor after cardiac death –non-heart beating donors

Question 6

What must be confirmed with DBD donors?

Answer 6

Irremediable structural brain damage of known cause
Apnoeic coma that is NOT due to depressant drugs, hypothermia, neuromuscular blockers etc.
Must be able to demonstrate a lack of brain stem function (e.g. pupils both fixed to light, no gag reflex etc)

Question 7

What must be excluded before harvesting organs from a deceased donor?

Answer 7

Viral infection
Malignancy
Drug abuse, overdose or poison
Disease of organ

Question 8

How are the organs maintained once they’ve been removed?

Answer 8

They are rapidly cooled and perfused

NOTE: absolute maximum cold ischaemia time for the kidneys is 60 hours, cornea is 96 hours

Question 9

What is the difference between transplant selection and transplant allocation?

Answer 9

Selection – access to the waiting list

Allocation – access to the organ

Question 10

What is the nationwide system of transplant allocation based on?

Answer 10

Equity – fairness

Efficiency – what is the best use of the organ in terms of patient and graft survival?

Question 11

What are the 5 tiers of patients on the organ transplant waiting list based on?

Answer 11

Paediatric or adult

Highly sensitised or not

Question 12

What are the 7 elements that are used to decide upon organ allocation?

Answer 12

Waiting time  
HLA match and age combined  
HLA-B homozygosity  
HLA-DR homozygosity  
Donor-recipient age difference  
Location of patient relative to donor  
Blood group match

Question 13

What are the main obstacles to donation?

Answer 13

Contraindication for use of that organ
Family not approached for consent
Family declined consent

Question 14

Describe some other strategies for increasing transplantation activity.

Answer 14

Increased decreased donation from marginal donors e.g. elderly and sick
Transplantation across compatibility barriers
Exchange programmes – organ swaps for better tissue matching
Future – xenotransplantation + stem cell research

Question 15

What are the main antigens that must be considered when determining the compatibility of an organ for transplant?

Answer 15

ABO

HLA

Question 16

On which chromosome is the HLA gene encoded?

Answer 16

Chromosome 6

Question 17

What are the two classes of HLA and which HLA subtypes are in each class?

Answer 17

HLA Class I – A, B and C = present on all cells

HLC Class II – DP, DQ, DR = present on APC’s

Question 18

What are the most important HLA subtypes in organ compatibility?

Answer 18

A
B
DR
NOTE: the fewer the number of mismatches, the better the outcome for the recipient

Question 19

What are the two types of organ rejection?

Answer 19

T cell-mediated rejection

Antibody-mediated rejection (B cells)

Question 20

How is rejection diagnosed?

Answer 20

Histological examination of graft biopsy

Question 21

How is rejection classified based on the time of onset and what are there corresponding types of organ rejection?

Answer 21

Hyperacute - T cell mediated
Acute - T cell mediated
Chronic - Antibody mediated (B cells)

Question 22

How may organ rejection present?

Answer 22

Deteriorating graft function e.g. rise in creatinine with kidney transplant, rise in LFT’s and coagulopathy w liver, breathlessness w lungs
Pain and tenderness over graft
Fever

Question 23

How can rejection be prevented?

Answer 23

Maximise HLA compatibility

Life-long immunosuppressive therapy

Question 24

List some treatments for Antibody-mediated (B cell) rejection.

Answer 24

Anti-CD20 antibodies  
Bortezomib (proteasome inhibitor)  
Anti-complement antibodies  
Plasma exchange  
IVIg 
Splenectomy

Question 25

What is normally used for baseline immunosuppression following transplantation?

Answer 25

Signal transduction blockade: CNI inhibitors usually a calcineurin inhibitor (tacrolimus or cyclosporin) Antiproliferative agent (e.g. azathioprine) Corticosteroids

Question 26

Describe the treatment of episodes of acute rejection.

Answer 26

T cell mediated: steroids and anti-T cell agents | Antibody mediated: IVIg, plasma exchange, anti-CD20, anti-complement

Question 27

What is a major risk of the extensive immunosuppressive therapy that is given to patients following transplantation?

Answer 27

Increased risk of infection (including opportunistic infection)

Question 28

List some treatments for T-cell mediated rejection.

Answer 28

Anti- CD3 AB's JAK3 inhibitors Azathioprine Cyclosporine

Question 29

What types of infections are you likely to get post-transplantation whilst on immune suppressive drugs?

Answer 29

``` Opportunistic Cytomegalovirus BK virus Pneumocytis carinii Murcormycosis ```

Question 30

Give of example of post-transplantation malignancy that may arise?

Answer 30

Skin cancer Lymphoproliferative disorder driven by EBV Kaposi's sarcoma

Question 31

What chance do you have to inherit the same HLA from your parents as your sibling?

Answer 31

You have a 25% chance of inheriting all of the same HLA (same 2 haplotypes) as any one of your siblings, you have a 25% chance of not inheriting any of the same HLA (none of the same haplotypes) and you have a 50% chance of sharing I haplotype with your siblings. Therefore, you have a 1 in 4 chance of being an identical match with your siblings.

Question 32

What is the most common solid organ transplanted in the UK?

Answer 32

Kidney | from both alive and dead donor

Question 33

What is the most common transplant in the UK?

Answer 33

Cornea, but is a tissue

Question 34

In which organs can HBO incompatible transplants be done and what else needs to occur?

Answer 34

Liver Heart Kidney Remove antibodies in recipient (plasma exchange)

Question 35

The transplantation of which organ/tissue does not need ABO blood group matching?

Answer 35

Cornea

Question 36

The 5 year survival rate for a heart transplant is approximately :

Answer 36

75%