Week 9 Part 1 - ABO Discrepancies and Transfusion in Transplantation Flashcards
ABO Grouping Discrepancies
An ABO discrepancy occurs when the forward and reverse grouping reactions don’t match
If blood is required before resolution of the discrepancy, issue Group O RBCs or AB plasma
What can a patient produce an anti-reagent antibody against, causing an ABO discepancy?
Dyes in Anti-A or Anti-B
Preservatives in reagent antibodies
Preservatives in reagent RBC preps
To prevent this - wash patient/reagent cells and resuspend in saline
B(A) Phenotype
Individuals produce high concentrations of B glycosyltransferase that catalyses the addition of D-Galactose AND N-acetyl-D- galactosamine
Mostly B antigen, with weak expression of A antigen, on RBCs
Produce an anti-A antibody that agglutinates A1 and A2 RBCs
With what antibody can the B(A) phenotype be detected?
Only detected when the MHO4 anti-A monoclonal antibody is used for forward grouping reactions
Solution - use a different grouping reagent
Results for B(A) Phenotype
Anti-A: 1+
Anti-B: 4+
A cells: 4+
B cells: 0
Acquired B
Group A individuals with gut diseases (Colon Ca, septicaemia)
Bacterial deacetylases remove acetyl group from GalNAc
Some anti-B reagents bind to D-galactosamine → w+ rxn
Not a true B antigen
Solution:
- use a different anti-B reagent
- decrease pH
Acquired B Results
Anti-A: 3+
Anti-B: 1+
A cells: 0
B cells: 4+
cisAB
In cisAB individuals, a single allele expressing both A AND B glycosyltransferases are inherited from an AB parent, and a single allele (usually O) from the other parent
cisAB individuals have decreased glycosyltransferase production → ↓ ag expression → weak forward reactions
Usually also produce a weak anti-B antibody
- reacts with B cells but not cisAB cells
Solution - family studies
cisAB Results
Anti-A: 2+
Anti-B: 2+
A cells: 0
B cells: 1+
Chimerism
Patient has two different populations of RBCs present in their circulation
Can be natural or acquired
Natural Examples of Chimerism
Multiple births (twins, triplets, etc)
Dispermy
Fetal-maternal bleed
Acquired Examples of Chimerism
Out-of-group transfusions
Bone Marrow/Stem Cell Transplants
Exchange Transfusion
Chimerism - Twin Chimerism
Placental blood vessels anastomose between twins
Blood flows between the twins
Haematopoietic cells engraft in the BM, → 2 sets of cells
Chimerism - Dispermy
Two sperm fertilise two maternal nuclei, and the resulting zygotes fuse to grow one body
Chimerism Results
Depends on the degree of the chimera
Solution:
- initially, patient history
- requires use of molecular methods to identify chimera
Types of Transplant
Autologous
- cells from own body
- for those in disease remission
Allogeneic
- cells from someone else
- for patients who can’t donate their own cells (chemo, irradiation, BM disease)
Syngeneic
- cells from identical twin
- for those with identical siblings (twins, triplets, etc)
- no chance of graft rejection, GvHD
Sources of Haematopoietic Progenitor Cells (HPCs)
Bone Marrow (BM)
Peripheral Blood
- collected via leukapheresis
- HPCs mobilised from BM using G-CSF (Filgrastim), Plerixafor, Chemo
Umbilical Cord Blood
Sample Preparation
CD34 counts (flow)
CD34 is a marker for HPCs
BM filtered to remove fat, debris, bone fragments
Separate buffy coat from RBCs/Plasma
- cell separator or Ficoll density gradient
- can enrich for CD34+ cells (magnetic beads/FACS)
ABO Incompatible Transplants - Major Mismatch
Foreign antigen on donor cells
Recipient produces antibody against donor cells
i.e. O recipient receives A cells
Recipient lyses donor RBCs, so they must be removed before transplantation
ABO Incompatible Transplants - Minor Mismatch
Foreign antibody in donor sample
Donor produces antibody against recipient cells
i.e. A recipient receives O cells
Aby’s in residual donor plasma lyse recipient RBCs
Passenger lymphocyte syndrome
- donor lymphocytes are infused into recipient
- donor lymphocytes produce aby → haemolysis
ABO Incompatible Transplants - Bi-Directional Mismatch
Major and minor mismatch (i.e. A recipient, B donor)
What Happens After Transplantation - Engraftment
Early
- 9-30 days
- ↑ neutrophil count
Platelet engraftment
- 15+ days
RBC engraftment/reconstitution
- 90+ days
How are RBCs and PLTs treated before being transplanted?
Leukoreduced and irradiated
Example of Transfusion Support in a Major Mismatch
O recipient, A donor as an example
Recipient will continue to have circulating anti- A, -B, -A,B for a period of time
Donor HPCs engraft, A RBCs produced, but will be lysed until recipient aby’s are cleared, hence transfusion requirement
Gp O RBCs (recipient group) transfused until recipient aby clears
PLT/FFP contain ABO antibodies
- we don’t want to transfuse the recipient with product that will lyse donor cell
Gp A PLT/FFP (donor group) transfused
Example of Transfusion Support in a Minor Mismatch
A recipient, O donor as an example
Donor HPCs engraft. Recipient RBCs eventually become group O
Gp O RBCs (donor group) transfused
PLT/FFP contain ABO antibodies
- we don’t want to transfuse the recipient with product that will lyse the recipient RBCs
Gp A PLT/FFP (recipient group) transfused
Overview of Transfusion Support in a Major and Minor Mismatch
In major:
- RBCs - same group as recipient
- PLT/FFP/Plasma product - same group as donor
In minor:
- RBCs - same group as donor
- PLT/FFP/Plasma product - same group as recipient
HSC Transplant Recipient - ABO Discrepancy with a Minor Mismatched Transplant
e.g. Group A recipient receives group O transplant
HSC Transplant Recipient - ABO Discrepancy with a Major Mismatched Transplant
e.g. Group O recipient receives group A transplant
Transfusion Support in ABO-Incompatible Solid Transplants
ABO-incompatible kidneys are transplanted
Largest concern is organ rejection due to a major mismatch
Recipient antibodies are reduced by plasmapheresis and immunosuppression
Aim in subsequent transfusions is to keep ABO antibody levels low
Blood products, particularly plasma (containing) products, must be ABO compatible with recipient AND graft for remainder of recipient’s life
Passenger lymphocyte syndrome can occur in minor mismatch recipients
- RBCs compatible with recipient and donor may be transfused to minimise this
