Haem - Blood transfusion

Question 1

What are ABO blood groups determined by

Answer 1

(1) antigens on RBC membrane
(2) naturally occurring IgM in the plasma
- IgM against normal RBC antigens
- IgG against atypical RBC antigens

Question 2

What are the types of blood group antigens

Answer 2

ABO
Rhesus
Kell (K)
M
N
S
Duffy (Fy) - delayed transfusion reaction
Kidd (Jk) - delayed transfusion reaction

Question 3

What happens when you give RhD +ve blood to a RhD -ve patient and what proportion of the population are RhD +ve

Answer 3

Formation of anti-D antibodies (IgG) → no acute reaction → DELAYED haemolytic reaction

15% RhD -ve

Question 4

Which blood group RBCs and plasma can you give to patients with blood group:
A
B
AB
O

Answer 4

RBCs:
A: A, O
B: B, O
AB: A, B, AB, O
O: O

Plasma:
A: A, AB
B: B, AB
AB: AB
O: A, B, AB, O

Question 5

What should be done before blood transfusion

Answer 5

Group and Screen - check ABO group and plasma antibodies in patient
Full crossmatch - patient’s blood against donor’s blood

Question 6

How does group and screen work

Answer 6

1. Mix known antibodies (A,B,D) against the patient’s RBCs
2. Add reverse group RBCs with the patient’s plasma (IgM)

Positive = agglutination at the top
Negative = red cells suspended at the bottom of the vial

Question 7

How does crossmatching work (antibody screens)

Answer 7

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

1. Use 2 or 3 reagent RBCs containing the important RBC antigens between thme
2. Incubate patient’s plasma and screening cells using Indirect antiglobulin technique (IAT)
   - Patient serum added to reagent RBCs
   - Add Anti-human globulin (AHG) to promote agglutination
   - If postitive, reaction creates bridges between RBCs coated with IgG → visible clumps

Question 8

How are RBCs stored and what is the infusion time

Answer 8

Stored at 4 degrees for 35 days
Transfuse in 4 hours of leaving the fridge
2-3 hours transfusion time for 1 unit

Question 9

How are platelets stored and what is the infusion time

Answer 9

22 degrees for 7 days
Transfusion time 20-30 minutes per unit

Question 10

How is plasma stored and what is the infusion time and why must it be given quickly

Answer 10

Plasma is frozen
Needs 30-40 minutes to thaw
- FFP: once thawed can keep at 4 degrees for 24 hours
- Cryoprecipitate: once thawed keep at room temp, use within 4 hours
20-30 minutes infusion time per unit
Stored at room temp → bacteria can contaminate quickly
A reaction with plasma is more likely to be allergic as plasma is frozen and so is unlikely to be contaminated by microbes

Question 11

What are the indications for blood transfusion

Answer 11

Major blood loss: >30% volume lost
Peri-op, critical care: Hb <70g/L
Post chemo: Hb <80g/L
Transfusion dependent: <70g/L (asymptomatic), <80g/L (symptomatic)
Symptomatic anaemia: IHD, SOB, ECG changes

(If iron/folate/B12 deficiency → treat this first unless they are actively bleeding)

Question 12

What are the cross matching requirements for plasma

Answer 12

ABO compatible, rhesus group does not matter
Do not need to cross match

Question 13

What are the options for autologous blood transfusion

Answer 13

Intra-operative cell salvage: blood collected in surgery, centrifuged, filtered, and washed before reinfusion

Post-operative cell salvage: a wound drain collects blood loss post-op, this is filtered and re-infused (seen in orthopaedic operations e.g. knee surgery)

Question 14

What are the special requirements for intra-uterine transfusions, neonatal transfusions, pregnant women, immunosuppressed patients, and those who have experienced severe allergic reaction

Answer 14

Intra-uterine, neonatal, pregnant women: CMV negative
Immunosuppressed: irradiated blood (pt cannot destroy incoming donor lymphocytes which would cause TA-GvHD)
Severe allergic reaction: washed

Question 15

What are the indications for platelet transfusion

Answer 15

Massive loss: Platelets <75x10^9
Preventing bleeding Post-chemo: <10x10^0
Preventing bleeding in Surgery: <50x10^9, <100 if a critical site e.g. eye, CNS
Platelet dysfunction or immune causes IF actively bleeding
Active bleeding + TTP, DIC, HIT

Question 16

What are the containdications to platelet transfusion

Answer 16

Heparin-induced thrombocytopaenia and thrombosis
Thrombotic thrombocytopenic purpura (TTP)

Question 17

What are the indications for fresh frozen plasma

Answer 17

Massive blood loss >150mil/min
DIC AND active bleeding
Liver disease + risk : PT ratio >1.5x normal
Coagulation factor replacement when factor concentrate is not available (contains all clotting factors)

Question 18

What does cryoprecipitate contain

Answer 18

More fibrinogen + FVIII and vWF, fibronectin, fVIII, platelet microparticles, IgA, albumin

Question 19

What defines acute reactions to transfusion and what are the types

Answer 19

<24hrs
Transfusion associated circulatory overload (TACO) - most common
Acute haemolytic (ABO incompatible)
Allergic/anaphylaxis
Infection (bacterial)
Febrile non-haemolytic
Acute lung injury (TRALI)

Question 20

What defines delayed reactions to transfusion and what are the types

Answer 20

> 24 hours
Delayed haemolytic transfusion reaction (antibodies) – Duffy and Kidd
Infection (viral, malaria, vCJD)
TA-GvHD (week or 2 after transfusion)
Post transfusion purpura
Iron overload

Question 21

What is SHOT (transfusion)

Answer 21

Serious hazards of transfusion
National reporting scheme for serious transfusion outcomes

Question 22

What are the early signs of an acute reaction and how may you pick these signs up in a patient who is unconscious

Answer 22

1. Raised temperature and pulse, reduce BP
2. General symptoms: fever, rigors, flushing, N&V, dyspnoea, chest pain, urticaria, itching, headache, collapse

Continuous monitoring
Before transfusion: baseline temp, RR, BP, pulse
Repeat post-transfusion: 15 mins and every hour

Question 23

Describe Febrile Non-Haemolytic Transfusion Reaction (FNHTR) and its treatment

Answer 23

Occurs during/soon after transfusion (blood or platelets)
(Now rare due to leucodepletion of blood)
Rise in temperature by around 1 degree, chills and rigors
Caused by the release of cytokines from white cells during storage

Tx: transfusion stopped or slowed and may need to be treated with paracetamol

Question 24

Describe allergic transfusion reactions and its treatment

Answer 24

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
Recipients have a history of atopy

Tx: IV antihistamines

Question 25

Describe ABO incompatibility reactions and what investigations should be done if suspected

Answer 25

Symptoms and signs of acute intravascular haemolysis (IgM-mediated): restless, chest/loin pain, fever, vomiting, flushing, collapse, haemoglobinuria (later)
Causes: failure of bedside check, wrongly labelled sample, lab error

Ix: FBC, Biochem, Coagulation, repeat X-match, DAT

Question 26

Describe bacterial contamination reactions in transfusion

Answer 26

Presents similarly to ABO mismatch
Bacterial growth can cause endotoxin production which causes immediate collapse
May be: from the donor (GI, dental, skin infection) OR introduced during processing (environmental or skin)
Platelets (stored at room temperature) > RBCs > FFP

Question 27

How is bacterial contamination in transfusion prevented

Answer 27

Donor questioning + arm cleaning + diversion of first 20 mL into a pouch (used for testing)
Platelets: stored for 7 days and screened for bacteria before release
Red Blood Cells: stored in a controlled fridge (4), if kept out >30 mins → put back in fridge for 6 hours

Question 28

Describe anaphylaxis during transfusion

Answer 28

Severe, life-threatening reaction soon after the start of transfusion → hypotension + tachy ± laryngeal/facial oedema, wheeze, SOB
Mechanism: IgE antibodiesin the patient cause mast cell degranulation
Increased severity of allergic reaction due to IgA deficiency

Question 29

Describe Transfusion Associated Circulatory Overload (TACO), its signs and symptoms and what investigations should be done

Answer 29

Most common acute transfusion reaction
Pulmonary oedema/fluid overload
Caused by lack of monitoring of fluid balance, especially in HF, renal impairment, hypoalbuminaemia
S/S: SOB, low sats (fluid overload), tachy and HTN (HF)
CXR: fluid overload

Question 30

Describe Transfusion Related Acute Lung Injury (TRALI)

Answer 30

Similar presentation to ARDS, NO fluid overload (unlike TACO)
More common in FFP or platelet transfusion
Anti-WBC Abs in the donor blood → react with pt WBCs → aggregates stick to pulmonary capillaries → neutrophil proteolytic enzymes + toxic O2 metabolites
Features: FEVER, SOB, low sats, high HR, high BP
CXR: bilateral pulmonary infiltrates during/within 6 hours of transfusion due to circulatory overload and other causes

Question 31

What is the difference in treatment response between TACO and TRALI

Answer 31

TACO responds to diuretics immediately (and has raised JVP)
TRALI does NOT respond to diuretics (no JVP)

Question 32

How is TACO and TRALI prevented

Answer 32

Use male donors for plasma and platelets (no pregnancy or previous transfusions, so no HLA/HNA ABs)

Question 33

Describe Delayed Haemolytic Transfusion Reaction and what investigations should be done

Answer 33

Usually to Duffy and Kidd antigens
Patients develop ABs against the RBC antigen they lack (alloimmunisation) → any further transfusions with those RBCs → extravascular haemolysis
IgG mediated, takes 5-10 days
Ix: bilirubin, FBC, LDH, reticulocytes, urine dip, DAT, U&Es

Question 34

Describe infection during transfusion as a delayed reaction

Answer 34

Anti-A, Anti-B = IgM antibodies | Anti-Rh, anti-Duffy, anti-Kidd = IgG antibodies
Examples = malaria, viral infections (CMV, parvovirus), variant CJD (“Mad Cow Disease)
Symptoms may occur months or years after the transfusion

Question 35

Describe Transfusion Associated Graft-Versus-Host Disease (TaGVHD)

Answer 35

Rare but ALWAYS FATAL
Can take weeks to months to come on after transfusion
Susceptible patient (immunosuppressed) do not destroy the donor lymphocytes → donor recognises patient HLA as foreign → attacks all HLA antigens (gut, liver, skin, bone marrow)
S/S: diarrhoea, liver failure, skin desquamation, bone marrow failure, death

Question 36

How is Transfusion Associated Graft-Versus-Host Disease (TaGVHD) prevented

Answer 36

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

Question 37

Describe post-transfusion purpura and its treatment

Answer 37

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)

Treatment: IVIG

Question 38

Describe iron overload

Answer 38

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

Question 39

What are the complications of haemolytic disease of the newborn

Answer 39

Foetal anaemia (haemolytic)
Haemolytic disease of the newborn (anaemia, high BR → builds up after birth as not removed by placenta)
Hydrops fetalis

Question 40

What is the pathophysiology of haemolytic disease of the newborn

Answer 40

1. RhD postive foetus → IgG Abs cross the placenta
2. Anti-D antibody development (sensitisation)
3. In subsequent pregnancies → RhD positive foetus → Abs cross the placenta and destroy foetal cells

Question 41

What is the prevention for haemolytic disease of the newborn

Answer 41

Group and screen and rhesus testing at booking (8-12) and at 28 weeks
If Rh- → anti-D Ig (foetal antigens removed by the spleen before sensitisation can occur)
If antibodies are present: check if father has antigen, monitor level of antibody + check ffDNA sample to allow for identification of baby’s RhD group
Monitor foetus for anaemia via MCA doppler US
May require early delivery OR intrauterine transfusion
- Via umbilical vein
- Monitor baby’s Hb and BR for several days
- May require exchamge transfusion

Question 42

When should anti-D be given

Answer 42

28 weeks (1500IU) if mother is RhD - OR 28 and 34 weeks
At delivery if the baby is RhD positive (1500IU)
Within 72 hours of a sensitising event
Foeto-maternal haemorrhage is likely to occur (and you do NOT know the Rh status of the baby)
+ Kleihauer test >20w to determine what dose is needed
- Spontaneous miscarriages if surgical evacuation needed and therapeutic terminations
- Amniocentesis and chorionic villous sampling (CVS)
- Abdominal trauma (falls and car accidents)
- External cephalic version (turning foetus)
- Stillbirth or intrauterine death

Question 43

What is the relevance of Anti-Kell antibodies, anti-A and anti-B antibodies in pregnancy

Answer 43

Kell causes reticulocytopenia in a foetus as well as haemolysis
Anti-A/anti-B: can cause mild HDN → treate with phototherapy