Blood transfusion

Question 1

what are examples of other blood group antigens other than ABO

Answer 1

o Other blood group antigens – Kell (K), M, N, S, Duffy (Fy), Kidd (Jk)
 Duffy and Kidd are known for causing delayed transfusion reactions
 The level of anti-Duffy and anti-Kidd decline with age

Question 2

Electronic crossmatching

Answer 2

o Compatibility is determined by an IT system without physical testing of donor cells against plasma
o This is a quick process, requiring fewer staff which allows better stock management

Question 3

serological crossmatch

Answer 3

o Full Crossmatch (uses IAT): checks blood against the DONOR’s blood specifically
 Patient’s plasma is incubated with donor red cells at 37 degrees for 30-40 mins
 Detects antibody-antigen reaction that destroys the RBCs leading to extravascular haemolysis
 Add antiglobulin reagent to cause cross-linking
 IgG antibodies bind to RBCs but do not crosslinking (why the AHG added in an IAT test)

Question 4

Immediate spin

Answer 4

 Incubate patient’s plasma and donor red cells for 5 minutes only and spin
 Will only detect ABO incompatibility
 IgM anti-A and/or anti-B bind to RBCs, fix complement and lyse the cell

Question 5

how does group and save work

Answer 5

• GROUP: Testing before transfusion – both of the below are done and included in a “Group and Screen”:
o (1) Use known anti-A, anti-B and anti-D reagents against the patient’s RBCs
o (2) Reverse group: known A and B groups red blood cells are mixed with the patient’s plasma (IgM antibodies)
 This group acts as an internal control – if it does not match, this is an anomalous result
 New-borns often have a weak reverse group as their ABs have not developed fully yet

o A positive result causes agglutination at the top
o A negative result will mean that the red cells stay suspended at the bottom of the vial
• SCREEN: Antibody screen:
o NOTE: it is impossible to test for all other RBC antigens because there are hundreds of them
o 1-3% of patients have developed antibodies to >1 RBC antigens (i.e. due to previous transfusion or pregnancy)
o Immune antibodies are IgG (these can cause a DELAYED transfusion reaction; extravascular haemolysis)
 As opposed to naturally occurring IgM antibodies (that cause an IMMEDIATE intravascular haemolysis)
o A 10-cell panel is used to identify RBC antibodies

o Antibody screen on patient’s plasma – avoid a delayed transfusion reaction with IgG antibodies…
 (1) use 2 or 3 reagent RBCs containing all important RBC antigens between them
 (2) incubate patient’s plasma and screening cells using the Indirect Antiglobulin Technique (IAT)
• (a) Patient serum containing specific antibody added to reagent RBCs
• (b) Add Anti-Human Globulin (AHG) to promote agglutination
• (c) If +ve, reaction creates bridges between RBCs coated in IgG antibodies  visible clumps

Question 6

why do you need to be careful with platelets

Answer 6

• The reason platelets need to be given more quickly is because they are stored at room temperature and so bacteria can contaminate it quite quickly  if patient develops a temperature stop the platelets and take blood cultures
o The platelets should then be sent back to the lab for microbiological testing

Question 7

MSBOS

Answer 7

 Based on negotiation between surgeons and transfusion lab about predictable loss for planned surgery
 Some operations rarely need blood whereas others will always need blood (e.g. AAA repair)
 For elective surgery, the patient should be group and screened before the operation
 If antibodies are not present, a crossmatch is NOT needed but the sample should be saved in the fridge
 If unexpected need for blood  provided <10 mins (by electronic issue as no antibodies are present)
 If antibodies are present, ALWAYS CROSSMATCH

Question 8

CMV negative blood

Answer 8

 Required for intra-uterine and neonatal transfusions

 Also used for elective transfusion in pregnant women

Question 9

irradiated blood

Answer 9

 Required for highly immunosuppressed patients
 As patients cannot destroy incoming donor lymphocytes
 Presence of these lymphocytes  fatal transfusion-associated graft-versus-host disease (TA-GvHD)

Question 10

washed blood

Answer 10

o	Washed (i.e. for IgA-deficient patients)
	RBCs/platelets given to patients who had severe allergic reactions to some donors' plasma proteins 
	This takes 4 hours to happen so needs to be pre-planned

Question 11

When is platelet transfusion contraindicated

Answer 11

o Heparin-induced thrombocytopaenia and thrombosis

o Thrombotic thrombocytopenic purpura (TTP)

Question 12

acute reactions to transfusion

Answer 12

o Acute haemolytic (ABO incompatible)
o Allergic/anaphylaxis
o Infection (bacterial)
o Febrile non-haemolytic
o Respiratory
 Transfusion associated circulatory overload (TACO)
• Often pre-existing cardiac/respiratory problems
• 1 in 100,000 mortality risk (very preventable)
• MOST COMMON ACUTE REACTION
 Acute lung injury (TRALI)

Question 13

delayed reactions to transfusion

Answer 13

o	Delayed haemolytic transfusion reaction (antibodies) – Duffy and Kidd 
o	Infection (viral, malaria, vCJD)
o	TA-GvHD (week or 2 after transfusion)
o	Post transfusion purpura
o	Iron overload

Question 14

Febrile non haemolytic transfusion reactions

Answer 14

• Occurs during/soon after transfusion (blood or platelets)
• May cause a rise in temperature by around 1 degree, chills and rigors
• Common before blood was leucodepleted (now rarer)
• Tx: transfusion stopped or slowed and may need to be treated with paracetamol
• Caused by the release of cytokines from white cells during storage

Question 15

allergic transfusion reactions `

Answer 15

• Common, especially with plasma (proteins in plasma)
• Causes a mild urticarial or itchy rash sometimes with a wheeze – caused by allergy to donor plasma proteins
• Can occur during or after (even after patient has left) transfusion  transfusion usually stopped or slowed
• Tx: IV antihistamines
• Recipients have a history of atopy

Question 16

ABO incompatibility

Answer 16

• Symptoms and signs of acute intravascular haemolysis (IgM-mediated):
o General: restless, chest/loin pain, fever, vomiting, flushing, collapse, haemoglobinuria (later)
o Monitoring: Low BP, High HR, High Temperature
• Causes:
o Failure of bedside check
o Wrongly labelled blood sample
o Laboratory error
• In cases where an acute haemolytic reaction may be taking place take samples for:
o FBC Biochemistry Coagulation
o Repeat X-match Direct antiglobulin test (DAT)

Question 17

bacterial contamination

Answer 17

• Presents similarly to ABO mismatch
o General: restless, fever, vomiting, flushing, collapse
o Monitoring: Low BP, High HR, High Temperature
• Bacterial growth can cause endotoxin production which causes immediate collapse
• The bacteria could have come from the donor (e.g. from low grade GI, dental or skin infection)
• The bacteria could have been introduced during processing (environmental or skin)
• Order of likelihood of contamination:
o Platelets (stored at room temperature) > RBCs > FFP

Question 18

anaphylaxis

Answer 18

• Severe, life-threatening reaction soon after the start of transfusion
o Shock = Drop in BP + Rise in HR
o Very breathless with wheeze
o Often laryngeal and/or facial oedema
• Mechanism: IgE antibodies in the patient cause mast cell degranulation
• Most allergic reactions are NOT severe, but some can be in the case of IgA deficiency
o IgA deficiency = 1: 600 [COMMON]
o In 25% of these, anti-IgA antibodies develop in response to exposure to IgA in the donor blood
o Only a minority go on to have a severe transfusion reaction

Question 19

transfusion associated circulatory overload

Answer 19

• VERY COMMON; leads to pulmonary oedema/fluid overload – a TACO checklist exists to help alleviate
• Often caused by lack of attention to fluid balance – especially in…
o Cardiac failure, renal impairment, hypoalbuminaemia, very young/old Clinical fluid overload

• Clinical features: CXR (fluid overload)
o SoB Low O2 saturations Fluid overload
o High HR High BP Cardiac failure

Question 20

Transfusion related acute lung injury

Answer 20

• Looks at bit like ARDS (more common in FFP or platelet transfusion) No clinical fluid overload
• Clinical features:
o SoB Low O2 saturations Fever
o High HR High BP
• CXR = bilateral pulmonary infiltrates during/within 6 hours of transfusion due to circulatory overload and other causes
• Mechanism:
o Anti-WBC antibodies in donor blood
o These interact with WBCs in the patient
o Aggregates WBCs stick to pulmonary capillaries  release neutrophil proteolytic enzymes and toxic O2 metabolites  lung damage (however, this mechanism is incompletely understood)

Question 21

delayed haemolytic transfusion reaction

Answer 21

• 1-3% of all patients transfused will develop an antibody against and RBC antigen that they lack = alloimmunisation
• Further transfusions with RBCs expressing same antigens  antibodies will lyse RBCs (extravascular haemolysis)
o This is IgG-mediated so takes 5-10 days
• Haemolysis Tests:
o High bilirubin Low Hb
o High reticulocytes Haemoglobinuria over a few days
• Test U&E because it can cause renal failure
• Repeat the group and screen and look for new antibodies that may have been made against the transfused red cells

Question 22

transfusion associated graft versus host disease

Answer 22

• Rare but ALWAYS FATAL (can take weeks to months to come on after transfusion)
• Pathophysiology:
o Donor’s blood will contain some lymphocytes that are able to divide
o Normally, the patient’s immune system will recognises these donor lymphocytes as foreign and destroy them
o In susceptible patients (very immunosuppressed), these lymphocytes are NOT destroyed
o Lymphocytes recognise patient’s tissue HLA antigens as foreign and attack (gut, liver, skin and bone marrow)

o Diarrhoea Liver failure Skin desquamation
o Bone marrow failure DEATH

Question 23

how to prevent graft versus host

Answer 23

• Prevention: irradiate blood components for very immunocompromised patients or have HLA-matched components

Question 24

post transfusion pupura

Answer 24

• Appears 7-10 days after transfusion of blood or platelets
• Usually resolves in 1-4 weeks but can cause life-threatening bleeding
• Affects Human Platelet Antigen (HPA) 1a -ve patients previously immunised via pregnancy or transfusion (HPA-1a AB)
• Exact mechanism is unknown
• Treatment: IVIG

Question 25

iron overload

Answer 25

o If someone has lots of transfusions (past thalassaemia patients), iron will accumulate in their body
o There is about 200-250 mg of iron per unit of blood
o This can damage the liver, heart and endocrine organs
o Requires chelation

Question 26

haemolytic disease of newborn

Answer 26

• Process:
o People lacking an RBC antigen (RhD) can form corresponding antibodies if exposed to the antigen
o This can happen:
 By receiving blood transfusions
 In pregnancy (foetal red cells enter the mother’s circulation during pregnancy or at delivery)
o In pregnancy, the first RhD-positive foetus will not experience any issues, however, they will stimulate the development of anti-D antibodies in the mother  in a subsequent pregnancy, if the mother has another RhD-positive foetus, the antibodies will destroy foetal red cells leading to severe anaemia ± HDN

• Only IgG antibodies can cross the placenta

 
• Consequences:
o Foetal anaemia (haemolytic)
o Haemolytic disease of the newborn (anaemia, high BR  builds up after birth as not removed by placenta)

Question 27

how does anti D immunoglobulin work

Answer 27

 The RhD +ve cells of the foetus will get coated by the exogenous anti-D immunoglobulin
 They will then be removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother to produce anti-D antibodies
 For this to be effective, the anti-D injection must be given within 72 hours of the sensitising event
 It does NOT work if the mother has already been sensitised and developed anti-D in the past

Question 28

how does anti D immunoglobulin work

Answer 28

 The RhD +ve cells of the foetus will get coated by the exogenous anti-D immunoglobulin
 They will then be removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother to produce anti-D antibodies
 For this to be effective, the anti-D injection must be given within 72 hours of the sensitising event
 It does NOT work if the mother has already been sensitised and developed anti-D in the past