Blood Transfusion 2

Question 1

What are 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)
• Acute lung injury (TRALI)

Question 2

What are 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

What are signs and symptoms of an acute adverse reaction to transfusion?

Answer 3

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

Symptoms: Depends on cause, but can include fever, rigors, flushing, vomiting, dyspnoea, pain at transfusion site, loin pain/ chest pain, urticaria, itching, headache, collapse etc.

Question 4

How are acute adverse reactions to transfusion detected?

Answer 4

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

Baseline temp, pulse, respiratory rate, BP before transfusion starts.

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

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

Question 5

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

Answer 5

Mild/moderate

During/soon after transfusion (blood or platelets), rise in temperature 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 6

What are allergic transfusion reactions?

Answer 6

Mild/moderate

Common especially with plasma.

Mild urticarial or itchy rash sometimes with a wheeze.

During or after transfusion.

Usually have to stop or slow transfusion IV antihistamines to treat (and 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 and atopy.

Question 7

What happens if the wrong blood is given?

Answer 7

Severe/fatal.

Symptoms and 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 and Direct Antiglobulin Test (DAT) Discuss with haematology doctor ASAP.

Question 8

Why are patients sometimes given the wrong blood?

Answer 8

Failure of bedside check giving blood

Wrongly labelled blood sample

Laboratory error

Question 9

What happens if bacterial contamination of product occurs?

Answer 9

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).

Introduced during processing (environmental or skin).

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

Question 10

How is bacterial contamination avoided?

Answer 10

Donor questioning

Arm cleaning

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

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

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

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

Question 11

What is anaphylaxis?

Answer 11

“Severe, life-threatening reaction soon after start of transfusion”

↓BP & ↑HR (shock), very breathless with wheeze, often laryngeal &/or facial oedema.

Mechanism: 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 IgA deficiency.

1:300 - 1:700 (common); where in 25%, anti-IgA antibodies develop in response to exposure to IgA (transfusion – especially with plasma); but only minority ever have transfusion reactions- frequency is 1:20,000 - 1:47,000.

Question 12

What are respiratory complications of transfusions?

Answer 12

Moderate, severe or fatal

Transfusion Associated Circulatory Overload (TACO)

Transfusion Related Acute Lung Injury (TRALI)

Transfusion Associated Dyspnoea (TAD)

Question 13

What is transfusion related circulatory overload (TACO)?

Answer 13

Pulmonary oedema/fluid overload.

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

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

CXR: Fluid overload/cardiac failure.

Question 14

What are increased risk factors for TACO?

Answer 14

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

Question 15

What is transfusion related acute lung injury (TRALI)?

Answer 15

Acute lung injury/ARDS.

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

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

Question 16

What is the aetiology of TRALI and how is it managed/prevented?

Answer 16

Mechanism: 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.

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

Question 17

How do infections present after blood transfusion?

Answer 17

Symptoms months or years after transfusion.

Rely on questioning donors about wellbeing.

Never zero risk – so don’t transfuse unnecessarily!

Question 18

What are other transfusion transmitted infections?

Answer 18

Malaria

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

Variant CJD.

Question 19

Which viruses can be transmitted via blood transfusion?

Answer 19

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

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

v-CJD: No test. Only 4 cases. but blood services exclude transfused patients as donors, as precaution. Also obtain plasma for those born after 01.01.1996, from outside the UK Since autumn last year decision reversed – now can use UK plasma for all.

COVID-19: Not transmitted by transfusion.

Question 20

What is a delayed haemolytic transfusion reaction?

Answer 20

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 5-10 days.

Question 21

What are tests for delayed haemolytic transfusion reactions?

Answer 21

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

Question 22

What is transfusion associated Graft-Versus-Host disease?

Answer 22

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

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

Lymphocytes recognise patient’s tissue HLA antigens as ‘foreign’ – so attack patient’s gut, liver, skin and bone marrow.

Prevent: Irradiate blood components for very immunosuppressed; or patients having HLA matched components.

Clinical features: Severe diarrhoea, liver failure, skin desquamation, bone marrow failure.

Question 23

What is post-transfusion purpura?

Answer 23

Purpura appears 7-10 days after transfusion of blood or platelets and usually resolves in 1 to 4 weeks but can cause life threatening bleeding.

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

Treatment: Infusion of IVIG

Question 24

What is immune modulation?

Answer 24

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

There are conflicting studies so it’s uncertain if this is true

Question 25

What is iron overload?

Answer 25

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 26

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

Answer 26

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

• By receiving blood transfusion
• 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 27

What are clinical features of HDFN?

Answer 27

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

• Fetal anaemia: Haemolytic
• Haemolytic disease of newborn: Anaemia plus high bilirubin - which builds up after birth as no longer removed by placenta

Question 28

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

Answer 28

All pregnant women have G&S at around 12 weeks (booking) and again at 28 weeks 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 ultrasound.
• Deliver baby early, as HDN gets a lot worse in last few weeks of pregnancy.

Question 29

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

Answer 29

If necessary, intra-uterine transfusion can be given to fetus. This is done at specialised centres, highly skilled - needle in umbilical vein.

At delivery - monitor baby’s Hb and bilirubin for several days as HDN can get worse for few days.

Can give exchange transfusion to baby if needed to bilirubin and Hb; plus phototherapy to bilirubin.

Note: Subsequent pregnancies usually worse.

Question 30

How is RhD antibody prevented?

Answer 30

Give Anti-D.

The most important antibody for causing HDFN but prevention is possible.

Prevention of sensitisation in first place: always transfuse RhD negative females of child bearing potential with RhD negative blood. Can give intra-muscular injection of anti-D immunoglobulin, at times when mother is at risk of a fetomaternal bleed e.g. at delivery.

Question 31

How does prophylactic anti-D immunoglobulins work?

Answer 31

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

To be effective you must give anti-D injection within 72 hours of the ‘sensitising event’. It does not work if the mother has already been sensitised (developed anti-D) in the past.

Question 32

What doses of anti-D must be given?

Answer 32

At least 250 iu - for events before 20 weeks of pregnancy.

At least 500 iu - for events any time after 20 weeks of pregnancy (including delivery).

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

Question 33

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

Answer 33

About 1% of pregnancies have no obvious ‘sensitising events’, yet RhD negative mothers become sensitised.

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

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

Question 34

What other antibodies can sensitise pregnant women?

Answer 34

Anti-c and anti-Kell can cause severe HDN.

Usually less severe than anti-D.

Kell causes reticulocytopenia in fetus as well as haemolysis IgG Anti-A and anti-B antibodies from Group O mothers can cause mild HDN.

Usually not severe (phototherapy).

Question 35

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

Answer 35

NHSBT offers fetal genotyping - support for routine maternity and transfusion services both nationally and internationally.

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

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

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

Question 36

What is the ffDNA technique and what does it do?

Answer 36

Currently anti-D (1500 IU) is administered at 28 weeks gestation as RADDP regime. At birth Baby is tested for Rh D status and further dose of 1500 IU is administered to mum to prevent sensitisation.

The ffDNA technique can predict Rh D status of fetus from 11+2 weeks gestation.

• At 16 weeks women can be consented for sample for ffDNA testing.
• Results available in 10 days.
• If baby Rh D negative – no anti D needed.