Blood Transfusion 2

Question 1

What are the 5 acute (<24 hours) adverse reactions to transfusions?

Answer 1

Acute haemolytic (ABO incompatible)

Allergic/ anaphylaxis

Infection (bacterial)

Febrile non-haemolytic

Respiratory:
* Transfusion associated circulatory overload (TACO)- more common than TRALI
* Acute lung injury (TRALI)

Question 2

What are the 5 delayed (>24 hours) adverse reactions to transfusions?

Answer 2

Delayed haemolytic transfusion reaction (antibodies).

Infection viral, malaria, vCJD.

TA-GvHD.

Post transfusion purpura.

Iron overload.

Question 3

How does an adverse reaction to transfusion present?

Answer 3

Many acute reactions start as a rise in temp or pulse or fall in BP before patient feels Sx.

Question 4

Give 10 possible symptoms of an adverse reaction to a transfusion

Answer 4

Fever + rigors
Flushing
Vomiting
Dyspnoea
Pain at transfusion site
Loin/ chest pain
Urticaria
Itching
Headache
Collapse

Question 5

How are acute adverse reactions to transfusion detected?

Answer 5

Monitoring may be the ONLY way to detect reaction if patient unconscious.

Baseline temp, pulse, RR, BP before transfusion starts.

Repeat after 15 mins (as most, but not all, reactions will start within 15 mins).

Ideally repeat hourly + at end of transfusion (as occasionally reactions start after transfusion finished).

Question 6

What is a febrile non-haemolytic transfusion reaction (FNHTR)?

Severity
Sx + Timing
Prevalence
Management
Cause

Answer 6

Mild/ moderate

During/ soon after transfusion (blood or platelets), rise in temp of 10C, chills, rigors.

Common before blood was leucodepleted, now rarer.

Have to stop or slow transfusion; may need to treat with paracetamol.

Cause: White cells can release cytokines during storage.

Question 7

What are allergic transfusion reactions?

Severity
Timing
Prevalence/ how common
Sx
Management
Cause

Answer 7

Mild/ moderate

During or after transfusion.

Common esp. with plasma.

Mild urticarial or itchy rash sometimes with a wheeze.

Usually have to stop or slow transfusion IV antihistamines to treat (+ prevent in future if recurrent).

Cause:

• Allergy to a plasma protein in donor so may not recur again, depending on how common the allergen is.
• Commoner in recipients with other allergies + atopy.

Question 8

What happens if the wrong blood is given?

Severity
Presentation
Management
Cause

Answer 8

Severe/ fatal.

Sx + signs of acute intravascular haemolysis- IgM.

Restless, chest/ loin pain, fever, vomiting, flushing, collapse, haemoglobinuria (later): ↓BP + ↑HR (shock), ↑Temp.

Stop transfusion: check patient / component.

Take samples for FBC, biochemistry, coagulation.

Repeat x-match + Direct Antiglobulin Test (DAT)
Discuss with haematology DR ASAP.

Question 9

Why are patients sometimes given the wrong blood?

Answer 9

Failure of bedside check giving blood

Wrongly labelled blood sample

Laboratory error

Question 10

What happens if bacterial contamination of product occurs?

Severity
Presentation
Prevalence
Cause

Answer 10

Severe/ fatal.

Similar to wrong blood reaction.
Restless, fever, vomiting, flushing, collapse. ↓BP + ↑HR (shock), ↑Temp.

Bacterial growth can cause endotoxin production which causes immediate collapse.

From the donor (low grade GI, dental, skin infection).
or
Introduced during processing (environmental or skin).

Platelets >red cells > frozen components (storage temp).

Question 11

How is bacterial contamination avoided?

Answer 11

Donor questioning

Arm cleaning

Diversion of first 20mL into a pouch (used for testing)

All components: Look for abnormalities e.g. clumps of discoloured debris; brown plasma etc.

Question 12

Describe storage of red cells and platelets
Temperature
Shelf life
Transfusion period

Answer 12

Red cells:
Store in controlled fridge 4C; shelf-life 35d.
If out for 30 mins, need to go back in fridge for 6h.
Complete transfusion of blood within 4h of leaving fridge i.e. transfuse over 4h max.

Platelets:
Stored at 22C; shelf-life 7d (as now screened for bacteria before release)
Transfuse over 20mins.

Question 13

What is anaphylaxis?

Answer 13

Severe, life-threatening reaction soon after start of transfusion

↓BP + ↑HR (shock)
very breathless with wheeze
often laryngeal +/- facial oedema.

Question 14

What is the mechanism of anaphylaxis?

Answer 14

IgE antibodies in patient cause mast cell release of granules + vasoactive substances.

Most allergic reactions are not severe, but few are e.g. in IgA deficiency-
1:300 - 1:700 (common);
where in 25%, anti-IgA antibodies develop in response to exposure to IgA (transfusion: esp. with plasma);
but only minority ever have transfusion reactions- freq is 1:20,000 - 1:47,000.

Question 15

What are 3 respiratory complications of transfusions?

Answer 15

Moderate, severe or fatal

Transfusion Associated Circulatory Overload (TACO)

Transfusion Related Acute Lung Injury (TRALI)

Transfusion Associated Dyspnoea (TAD)

Question 16

What is the most common cause of pulmonary complication post transfusion? Describe the onset of this in relation to the transfusion

Answer 16

TACO
Majority present within 6h of transfusion

Question 17

What is transfusion related circulatory overload (TACO)?

Answer 17

Pulmonary oedema/ fluid overload.

Often lack of attention to fluid balance, esp. in cardiac failure, renal impairment, hypo-albuminaemia, those on fluid replacement, very young, very small + very old.

Clinical features: SOB, ↓SAO2 , ↑HR, ↑BP

CXR: Fluid overload/ cardiac failure.

Question 18

What are increased risk factors for TACO?

Answer 18

• Hypoalbuminaemia
• Positive fluid balance prior to transfusion
• Concomitant IV fluids
• Chronic kidney disease
• Diuretic use
• Liver dysfunction
• Cardiac disease
• Peripheral oedema
• Weight <50kg
• Respiratory Sx of undiagnosed cause
• Pulmonary oedema

Question 19

What is transfusion related acute lung injury (TRALI)?

Answer 19

Acute lung injury/ ARDS.

SOB, ↓O2, ↑HR, ↓BP; (similar to TACO).

CXR: Bilateral pulmonary infiltrates during/ within 6h of transfusion, not due to circulatory overload or other likely causes.

Question 20

What is the mechanism of TRALI?

Answer 20

Anti-wbc antibodies (HLA or neutrophil Abs) in donor.
Interact with corresponding ag on patient’s WBCs.
Aggregates of WBCs get stuck in pulmonary capillaries → release neutrophil proteolytic enzymes + toxic O2 metabolites → lung damage.

Mechanism not fully understood, antibodies don’t always cause problems.

Question 21

What is done for prevention of TRALI?

Answer 21

Male donors for plasma + platelets (no pregnancy or transfusion, so no HLA/ HNA antibodies).

Question 22

How do infections present after blood transfusion?

Answer 22

Sx months or years after transfusion.
HBV, HCV, HIV

Rely on questioning donors about wellbeing.

Never 0 risk – so don’t transfuse unnecessarily!

Question 23

What are other transfusion transmitted infections?

Answer 23

Malaria

Viral infection: HIV 1+2, HEV, HBV, HCV, HTLV 1+2, Parvovirus, CMV, WNV, Zika.

Variant CJD.

Question 24

Which viruses can be transmitted via blood transfusion?

Answer 24

CMV: Very immunosuppressed (SCT) patients can get fatal CMV disease, but leucodepletion removes CMV (in wbc’s) Only give CMV -ve now for pregnant women (foetus) + neonates.

Parvovirus: Causes temporary red cell aplasia - affects foetuses + patients with haemolytic anaemias e.g. sickle cell; hereditary spherocytosis.

v-CJD: No test. Only 4 cases. Blood services exclude transfused patients as donors, as precaution. Also obtain plasma for those born after 1996, from outside the UK (Since autumn last year decision reversed – now can use UK plasma for all)

COVID-19: Not transmitted by transfusion.

Question 25

What is a delayed haemolytic transfusion reaction?

Answer 25

1-3% of all patients transfused develop an ‘immune’ antibody to a RBC antigen they lack
=Allomunisation.

If the patient has another transfusion with RBCs expressing the same antigen, antibodies cause RBC destruction =Extravascular haemolysis (as IgG) so takes 5-10d.

Question 26

What are tests for delayed haemolytic transfusion reactions?

Answer 26

Haemolysis screen
* Bilirubin ↑
* LDH ↑
* Retics ↑
* Hb ↓
* DAT (+ve)
* Haemoglobinuria over few days
* Test U&Es – as can cause renal failure
* Repeat G&S for ? new antibody

Question 27

What is transfusion associated Graft-Versus-Host disease?

Answer 27

Rare, but always fatal (death weeks to months post transfusion).

Donor’s blood contains lymphocytes (able to divide). Normally, patient’s immune system recognises donor’s lymphocytes as ‘foreign’ + destroys them.
In ‘susceptible’ patients (very IS)- lymphocytes not destroyed.

Lymphocytes recognise patient’s tissue HLA antigens as ‘foreign’– so attack patient’s gut, liver, skin + BM.

Question 28

Give 4 clinical features of TaGVHD

Answer 28

Severe diarrhoea
Liver failure
Skin desquamation
Bone marrow failure.

Question 29

How can TaGVHD be prevented?

Answer 29

Irradiate blood components for very immunosuppressed;
or give HLA matched components.

Question 30

What is post-transfusion purpura?

Answer 30

Purpura appears 7-10d after transfusion of blood or platelets + usually resolves in 1-4w but can cause life threatening bleeding.

Affects HPA-1a -ve patients: previously immunised by pregnancy or transfusion (anti-HPA-1a antibody).

Tx: Infusion of IVIG

Question 31

What is immune modulation?

Answer 31

Possible increased rate of infections post-op + increased recurrence of cancers in patients who have blood transfusion.

Conflicting studies- uncertain if this is true

Question 32

What is iron overload?

Answer 32

If lots of transfusion (e.g. >50) over time accumulate iron (not excreted):

200-250mg of iron per unit of blood.

Can cause organ damage - liver, heart, endocrine etc.

Prevent by iron chelation (Exjade) with transfusions once ferritin >1000 e.g. used in Thalassaemia/ Sickle cell disease: regular transfusions.

Question 33

What is Haemolytic Disease of the (Fetus &) Newborn?

Answer 33

People lacking a red cell antigen can form corresponding antibody if exposed to antigen eg: RhD-ve patient forms anti-D

• By receiving blood transfusion (RhD+ve)
• In pregnancy - by fetal red cells entering mother’s circulation at delivery or during pregnancy.

Some antigens are more likely to stimulate antibodies than others.

Question 34

What are clinical features of HDFN?

Answer 34

Only IgG antibodies can cross the placenta.
If mother has high levels of IgG antibody - it can destroy fetal red cells, if they are +ve for the corresponding antigen. The 2 main consquences are:

• Fetal anaemia: (Haemolytic)
• Haemolytic disease of newborn: Anaemia + high BR- which builds up after birth as no longer removed by placenta

Question 35

What is the treatment in pregnancy when mother already has the red cell antibody?

Answer 35

All pregnant women have G+S at ~12w (booking) + again at 28w to check for RBC Antibodies. If antibody present:

• Check if father has the antigen (so baby could inherit it)
• Monitor level of antibody (high or rising - more likely to affect fetus).
• Check ffDNA sample.
• Monitor fetus for anaemia– MCA Doppler USS.
• Deliver baby early, as HDN gets a lot worse in last few weeks of pregnancy.

Question 36

In an emergency, what can be used to treat pregnant, sensitised RhD-ve women?

Answer 36

Intra-uterine transfusion can be given to fetus.
Done at specialised centres, highly skilled - needle in umbilical vein.

At delivery: monitor baby’s Hb + BR for several days as HDN can get worse for few days.

Can give exchange transfusion to baby if needed to BR + Hb; plus phototherapy to BR.

Note: Subsequent pregnancies usually worse.

Question 37

How is RhD antibody prevented?

Answer 37

Give Anti-D.

Most important antibody for causing HDFN but prevention is possible.

Prevention of sensitisation in first place: always transfuse RhD-ve females of child bearing potential with RhD-ve blood.

Can give IM injection of anti-D immunoglobulin, at times when mother is at risk of a fetomaternal bleed e.g. at delivery.

Question 38

How does prophylactic anti-D immunoglobulins work?

Answer 38

RhD+ve (fetal) red cells get coated with anti-D Ig + then get removed by the mother’s reticulo-endothelial system (spleen) before they can sensitise the mother to produce anti-D antibodies.

To be effective: must give anti-D injection within 72h of the ‘sensitising event’.

Does not work if the mother has already been sensitised (developed anti-D) in the past.

Question 39

In what 7 events should anti-D be given? (sensitising events)

Answer 39

At delivery if baby is RhD+ve
Spontaneous miscarriage if surgical evac
TOP
Amniocentesis + CVS
Abdominal trauma e.g. fall
ECV
Stillbirth or IU death

Question 40

What doses of anti-D must be given?

Answer 40

At least 250 iu: if before 20w of pregnancy.

At least 500 iu: if any time after 20w of pregnancy (inc. delivery).

Question 41

When are larger doses of anti-D required? How is this determined?

Answer 41

Larger dose is needed for larger bleeds, so an FMH test (Kleihauer test) is always done if > 20w pregnant + at delivery, to determine if more anti-D is needed than the standard dose, if the fetal bleed is large.

Question 42

What is routine antenatal anti-D prophylaxis (RAADP)?

Answer 42

~1% of pregnancies have no obvious ‘sensitising events’, yet RhD-ve mums become sensitised.

To prevent this, routine anti-D prophylaxis can be given in 3rd trimester.

Usually, dose of 1500 iu anti-D Ig at 28-30w.

Question 43

What other antibodies can sensitise pregnant women?

Answer 43

Anti-c + anti-Kell can cause severe HDN.
Usually less severe than anti-D.
Kell causes reticulocytopenia in fetus as well as haemolysis

IgG Anti-A + anti-B antibodies from Group O mothers can cause mild HDN.
Usually not severe (phototherapy).

Question 44

What is non-invasive fetal genotyping for mothers with antibodies?

Answer 44

NHSBT offers fetal genotyping: support for routine maternity + transfusion services both nationally + internationally.

A rapid, non-invasive, convenient + reliable service for prediction of fetal D, C, c, E + K status, using cell-free fetal DNA in maternal blood for women who have alloantibodies.

Upon identification, mums can then be informed + prepared for further careful monitoring during their pregnancy.

Also identifies pregnant women who have antigen -ve fetuses + who therefore are not at danger from HDFN.

Question 45

What is the ffDNA technique and what does it do?

Answer 45

Can predict RhD status of fetus from 11+2w gestation.

• At 16w women can be consented for sample for ffDNA testing.
• Results available in 10d.
• If baby RhD-ve: no anti D needed.

Question 46

Describe the current policy on anti-D in pregnancy

Answer 46

Anti-D (1500 IU) is administered at 28w gestation as RADDP regime.
At birth Baby is tested for RhD status + further dose of 1500 IU is administered to mum to prevent sensitisation.