Blood Transfusions 2

Question 1

What are the two categories of adverse reactions to transfusions (2)

Answer 1

Acute < 24 hours

Delayed >24 hours

Question 2

What are some acute adverse reactions to transfusions (6)

Answer 2

Acute haemolysis (ABO incompatible) 
Allergic/anaphylaxis
Infection (bacterial)
Febrile non-haemolytic
Respiratory (transfusion associated circulatory overload (TACO), acute lung injury (TRALI)

Question 3

What are some delayed adverse reactions to transfusions (5)

Answer 3

Delayed haemolytic transfusion reaction (antibodies) 
Infection (viral, malaria, vCJD)
TA-GvHD
Post transfusion purpura 
Iron overload

Question 4

How are acute transfusion reactions picked up (3)

Answer 4

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

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 are FNHTR

Answer 5

Febrile Non-Haemolytic Transfusion Reaction.

During / soon after transfusion (blood or platelets), rise in temperature of 1C, chills, rigors
Common before blood was leucodepleted, now rarer

Question 6

How are FNHTR treated (2)

Answer 6

Have to stop or slow transfusion - may need to treat with paracetamol

Question 7

What is the MOA of FNHTR

Answer 7

White cells can release cytokines during storage

Question 8

What are allergic transfusion reactions

Answer 8

Common especially with plasma

Mild urticarial or itchy rash sometimes with a wheeze. During or after transfusion.

Question 9

How are allergic transfusion reactions treated (2)

Answer 9

Have to stop or slow down transfusion

IV antihistamines to treat (and prevent in future, if recurrent)

Question 10

What causes allergic transfusion reactions (2)

Answer 10

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 11

What causes acute intravascular haemolyiss

Answer 11

WRONG BLOOD - IgM reaction

Question 12

What are the symptoms of giving a patient the wrong blood

Answer 12

Restless, chest/ loin pain, fever, vomiting, flushing, collapse, haemoglobinuria (later);
Raised temperature
Raised heart rate
Low BP

Question 13

What can be some reasons for wrong blood administered for transfusion (3)

Answer 13

Failure of bedside check giving blood
Wrongly labelled blood sample
Lab error

Question 14

How is wrong blood given at transfusion managed (3)

Answer 14

Take samples for FBC, biochemistry, coagulation, repeat x-match and Direct Antiglobulin Test (DAT).

DISCUSS WITH HAEMATOLOGY ASAP

Question 15

What are the symptoms of transfusion of bacterial contaminated blood

Answer 15

Restless, fever, vomiting, flushing, collapse

Low BP, high HR, high temp

Question 16

What causes bacterial contamination of transfused blood (4)

Answer 16

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)
Storage temperatures (platelets > red cells > frozen components)

Question 17

How can we prevent contamination of donor blood (4)

Answer 17

Donor questioning + arm cleaning + diversion of first 20mL into a pouch (used for testing)
Red cells: Store always in controlled fridge 40C; shelf-life 35 days. If out for >½ hour, need to go back in fridge for 6 hours. Complete transfusion of blood within 4.5h of leaving fridge i.e. transfuse over 4hrs max
Platelets: stored at 220C; shelf-life 7 days (as now screened for bacteria before release)
All components: look for abnormalities e.g. clumps of discoloured debris; brown plasma etc

Question 18

What is post-transfusion anaphylaxis

Answer 18

Immediate reaction

Severe, life threatening reaction soon after start of transfusion

Question 19

What are the signs of anaphylaxis post transfusion

Answer 19

Low BP and high HR (shock)
Very breathless with wheeze
Often laryngeal and/or facial oedema

Question 20

What is the mechanism of anaphylaxis following blood transfusion

Answer 20

IgE antibodies in patient cause mast cell release of granules & vasoactive substances. Most allergic reactions are not severe, but some can be e.g. in
IgA deficiency:

Question 21

What is TACO

Answer 21

Transfusion associated circulatory overload

Question 22

What occurs in TACO

Answer 22

Pulmonary oedema/fluid overload

Question 23

When does TACO occur

Answer 23

Often lack of attention to fluid balance, especially in cardiac failure, renal impairment, hypoalbuminaemia, very young and very old

Question 24

What are the clinical features of TACO

Answer 24

SOB
Low O2 sats
high HR
High BP

Question 25

What is seen on CXR in TACO (2)

Answer 25

Fluid overload | Cardiac failure

Question 26

What is TRALI

Answer 26

Transfusion related acute lung injury

Question 27

What are the clinical features of TRALI

Answer 27

SOB Low O2 sats high HR High BP

Question 28

What is seen on CXR in TRALI

Answer 28

Bilateral pulmonary infiltrates during/within 6 hours of transfusion due to circulatory overload or other likely causes

Question 29

What is the MOA of TRALI

Answer 29

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

Question 30

How can TRALI be prevented

Answer 30

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

Question 31

What are the two steps involved in delayed haemolytic transfusion reactions

Answer 31

``` Allommunisation Extravascular haemolysis (as IgG) so takes 5-10 days ```

Question 32

What is allommunisation

Answer 32

1-3% of all patients transfused develop an immune antibody to a RBC antigen they lack

Question 33

What is extravascular haemolysis

Answer 33

If the patient has another transfusion with RBCs expressing the same antigen (that they just became allomminised against), antibodies cause RBC destruction

Question 34

What is seen in biochemistry tests in delayed haemolytic transfusion reaction

Answer 34

``` Raised Bilirubin Low Hb High retics Haemoglobinuria over a few days U&Es have to be tested - as can cause renal failure ```

Question 35

What infections can be transferred via blood transfusion (3)

Answer 35

Malaria Viral infection Variant CJD

Question 36

What are the features of infections from blood transfusions

Answer 36

Symptoms months or years after Rely on questioning donors about wellbeing Never zero risk – so don’t transfuse unnecessarily! Current estimates of getting viral infection from a donation: hepatitis B – 1 in 1.3 million, HIV – 1 in 6.5 million, hepatitis C – 1: 28 million

Question 37

What is the risk of CMV from blood transfusion

Answer 37

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 (fetus) & neonates.

Question 38

What is the risk of parvovirus from blood transfusion

Answer 38

causes temporary red cell aplasia - affects fetuses and patients with haemolytic anaemias eg: sickle cell; hereditary spherocytosis

Question 39

What is the risk of vCJD from blood transfusion.

Answer 39

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

Question 40

What are the features of transfusion associated graft-versus-host disease

Answer 40

Rare, but always fatal 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 (eg.. very IS) - lymphocytes not destroyed Lymphocytes recognise patient’s tissue HLA antigens as ‘foreign’ – so attack patient’s gut, liver, skin and bone marrow - Causes severe diarrhoea, liver failure, skin desquamation, bone marrow failure  death weeks to months post transfusion

Question 41

How can transfusion associated graft versus host disease be prevented (2)

Answer 41

Irradiate blood components for very immunocompromised or patients having HLA matched components

Question 42

What is post transfusion purpura

Answer 42

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)

Question 43

How is post transfusion purpura treated

Answer 43

IVIG

Question 44

What causes the purpura in post-transfusion purpura

Answer 44

Very low platelets of <20

Question 45

What is a risk in immune modulation post blood transfusion

Answer 45

Can increase risk of infections post-op and increased recurrence of cancers

Question 46

What are the features of iron overload following transfusion

Answer 46

If lots of transfusion (eg:>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 eg: used in Thalassaemics - monthly transfusions

Question 47

How can anti-D be formed (2)

Answer 47

By receiving blood transfusion | In pregnancy - by foetal red cells entering mother's circulation at delivery or during pregnancy

Question 48

MOA of RhD sensitisation during the first pregnancy and foetal red cell destruction during the second pregnancy with a RhD positive foetus

Answer 48

1st pregnancy: Foetal RhD positive red cells cross the placenta mainly during delivery. AntiD forms in the mother approximately 6 months later. 2nd pregnancy: RhD positive foetus. Maternal antiD crosses the placenta and coats the foetal RhD positive red cells and destroys them in the foetal spleen and liver.

Question 49

What are the clinical features of haemolytic disease of the newborn

Answer 49

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: Fetal anaemia (haemolytic), Haemolytic disease of newborn (anaemia plus high bilirubin - which builds up after birth as no longer removed by placenta) Sequelae include hydrops fetalis, kernicterus.

Question 50

How is a pregnancy managed when the mother already has red cell antibody.

Answer 50

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 If necessary, intra-uterine transfusion can be given to the foetus

Question 51

What are the points where intra uterine transfusion can be given to the foetus (3)

Answer 51

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 lower bilirubin and raise Hb; plus phototherapy to lower bilirubin

Question 52

What is the most important antibody is HDFN

Answer 52

Anti-D

Question 53

How can sensitisation to anti-D be prevented

Answer 53

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 54

How does prophylactic anti-D immunoglobulin work

Answer 54

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

Question 55

When is anti-D immunoglobulin effective

Answer 55

Must give anti-D injection within 72 hours of the sensitising event

Question 56

When is anti-D immunoglobulin not effective

Answer 56

If the mother has already been sensitised in the past

Question 57

Management: Delivery of RhD positive baby

Answer 57

Give anti-D to mother at delivery

Question 58

When should you give anti-D to the mother (2)

Answer 58

At delivery if baby is RhD positive | For sensitising events during pregnancy (where HDFN if most likely to occur)

Question 59

What are some sensitising events for anti-D during pregnancy (5)

Answer 59

Spontaneous miscarriages if surgical evacuation needed and therapeutic terminations Amniocentesis and chorionic villous sampling Abdominal trauma (falls and car accidents) External cephalic version (turning the fetus) Stillbirth or intrauterine death

Question 60

What is the dose of anti-D given (3)

Answer 60

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 61

What dose of anti-D can prevent sensitisation from a 1mL FMH

Answer 61

125iu

Question 62

What is RAADP

Answer 62

Routine antenatal anti-D prophylxis

Question 63

Whe is anti-D routinely given

Answer 63

3rd trimester Usually, dose of 1500iu anti-D Ig at 28-30 weeks. Can prevent MOST RhD negative women from becoming sensitised

Question 64

What are the antibodies that can affect the baby during pregnancy (5)

Answer 64

Anti-D, Anti-C, anti-Kell cause severe HDN (anti-D is the worst, Kell causes reticulocytopenia in the foetus as well as haemolysis) IgG anti-A and anti-B antibodies from Group O mothers can cause mild HDN (usually not severe - phototherapy)