HAEM: Blood transfusion Flashcards
1
Q
Which two ways help determine ABO blood groups?
A
- Determined by
- (1) antigens on RBC membrane,
- (2) naturally occurring IgM in the plasma
- IgG reacts against atypical RBC antigens
- IgM reacts against normal RBC antigens
2
Q
Apart from ABO, list some other blood group antigens.
A
- 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
3
Q
What is the consequence of giving ABO incompatible blood vs other antigen incompatible(e.g. Duffy and Kidd)?
A
ABO - Massive intravascular haemolysis
Duffy and Kidd - delayed transfusion reaction, but the antibodies against these decline with age
4
Q
What % of population are RhD -ve?
A
15% (85% are RhD positive)
5
Q
What is the consequence of giving RhD +ve to an RhD-ve patient?
A
Will sometimes induce formation of Anti-D this does not cause any acute problem and will be picked up by the lab next time they need blood
6
Q
What is the problem of making anti-RhD in pregnancy and having an RhD-ve fetus?
A
Anti-D made by an Rh -ve mother exposed to Rh +ve blood –> haemolytic disease of the newborn or severe fetal anaemia and heart-failure (hydrops fetalis) in RhD -ve females of child bearing potential
7
Q
What is the difference between crossmatch and group and save?
A
GROUP and SCREEN – check ABO group and plasma antibodies in patient (done each time it is requested for that patient)
Full crossmatch – checks patient’s blood against donor blood specifically
8
Q
How is blood GROUP testing carried out?
A
- (1) Use known anti-A, anti-B and anti-D reagents against the patient’s RBCs
-
(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
- A positive result causes agglutination at the top
- A negative result will mean that the red cells stay suspended at the bottom of the vial
9
Q
How is blood SCREEN carried out?
A
- 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 à visible clumps
- https://youtu.be/PozNhjmxvG0?t=44 = good distinction of the types of Coomb’s test!
10
Q
Why do you do a group and save every time?
A
SCREEN: Antibody screen:
It is impossible to test for all RBC antigens
1-3% of patients have developed antibodies to >1 RBC antigens (i.e. due to previous transfusion or pregnancy)
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)
A 10-cell panel is used to identify RBC antibodies
11
Q
What kind of panel and how many components are used in antibody screening in blood?
A
10-cell panel is used
12
Q
How is SEROLOGICAL crossmatching done? Which method is only done in emergency?
A
-
Serological crossmatching:
-
Full Crossmatch (uses IAT):
- 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)
- Immediate Spin [EMERGENCY Scenario Only]:
- 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
-
Full Crossmatch (uses IAT):
13
Q
When is Kell antigen negative blood specifically given?
A
Women of child-bearing age
14
Q
What is the traceability tag on blood?
A
Allows for 100% traceability from donor to recipient
Kept for 30 years
15
Q
What is the use of ELECTRONIC crossmatch?
A
Compatibility of blood determined by IT system without physical testing of donor cells against plas,a
This is quick and less staff involved and better stock management
16
Q
What are the pillars of blood transfusion?
A
17
Q
How quickly is each blood component given and how is each stored?
A
18
Q
What are the indications for a blood transfusion in a patient?
A
- Is the patient bleeding?
- What are the blood results?
- Is the patient symptomatic?
- Will a transfusion solve the problem?
- What are the risks of transfusion?
- Are there alternative treatments?
19
Q
If the patient is male, what blood is given in an emergency?
A
O positive
20
Q
Why is plasma tranfusion given quicker?
A
- 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
- The platelets should then be sent back to the lab for microbiological testing
- A reaction with plasma is more likely to be allergic as plasma is frozen and so is unlikely to be contaminated by microbes
21
Q
Which component should be compatible when giving RBC/ platelets/ plasma? How long can thawed FFP be used vs cryoprecipitate?
A
FFP - kept for 24hrs once thawed, kept at 4oC
Cryo - used over 24, kept at RT
22
Q
Describe the MSBOS.
A
MSBOS = maximum surgical blood ordering schedule
- 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
23
Q
What are the indications and triggers for RBC transfusions?
A
24
Q
What are the indications and triggers for platelet transfusion? When is this transfusion best given?
A
During the procedure
25
What are the contraindications to platelet transfusion?
* Contraindications:
* Heparin-induced thrombocytopaenia and thrombosis
* Thrombotic thrombocytopenic purpura (TTP)
26
What rise in plt does 1 unit of platelets cause?
* 1 unit of platelets --\> increase platelet count by 30-40 x 109/L
## Footnote
*Platelet dysfunction can be caused by drugs (e.g. aspirin, clopidogrel)*
27
What are the indications and triggers for FFP transfusion?
NB: no longer just collected from non-UK donors
28
What is best used for transfusion when trying to reverse warfarin?
Not FFP - this contains all clotting factors
Prothrombin complex concentrate (PCC) - contains factors 2, 7, 9, 10
29
Which blood components are GROUP matched but not crossmatched?
Platelets and FFP
30
How are blood bottles labelled?
At the bedside
## Footnote
**Hand-written labels**
31
What instances can patients get their own blood during a surgery?
32
When is CMV negative/irradiated/washed blood used?
33
When can O positive blood be given in an emergency?
Females over 50 and males
34
What can be given instead of blood in a major transfusion lasting \<3 hours? When is this contraindicated? What is done is these steps do not work?
TXA 1g bolus followed by 1g over 8 hours
Contraindicated in GI bleeding
If bleeding continues give 1:1 RBC:FFP usually 4 units of each. Fibrinogen concentrate 50mg/kg if more than 4 units of blood transfused.
35
List some types of acute reactions (\<24 hours) with blood transfusion.
1. Acute haemolytic (ABO incompatible)
2. Allergic/anaphylaxis
3. Infection (bacterial)
4. Febrile non-haemolytic
5. Respiratory
1. **Transfusion associated circulatory overload** (**TACO**)
* **MOST COMMON ACUTE REACTION**
* 1 in 100,000 mortality risk (very preventable)
* Often pre-existing cardiac/respiratory problems
2. Acute lung injury (**TRALI**)
36
List some examples of delayed transfusion reactions (\>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
37
What is SHOT and how does it divide transfusion reaction?
SHOT - serious hazard of trasfusion
1. Non-preventable pathological reactions
2. Preventable reactions (through improved practice)
3. Adverse events caused by error
38
What are the FIRST signs of an acute reaction?
* **Rise in temperature or pulse**
* **Drop in BP**
39
What are 5 other general symptoms of acute reaction to transfusion?
* Fever
* Rigors
* Flushing
* Vomiting
* Dyspnoea
* Pain at transfusion site
* Loin pain/chest pain
* Urticaria
* Itching
* Headache
* Collapse
40
If the patient is unconscious how do you detect the transfusion reaction?
* MONITORING
* **Baseline** temperature, pulse, RR, BP before transfusion
* **Repeat after 15 mins** (most reactions start within 15 mins)
* 0min--\> 15m--\> 1hr --\> 1hr… --\> end
* **Repeat hourly** and at the end of the transfusion
41
What is FNHTR and when does it occur? Why is it less common now? How is it treated?
**Febrile Non-Haemolytic Transfusion Reaction = MILD/MODERATE**
* 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_**)
* Caused by the **release of cytokines from white cells** during storage
**Tx**: transfusion stopped or slowed and may need to be treated with paracetamol
42
Describe the cause of allergic transfusion reactions. When does it occur? Which patients? How is it treated?
* **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 à transfusion usually stopped or slowed
* Recipients have a history of **atopy**
**Tx:** **IV antihistamines**
43
Describe the signs and symptoms associated with ABO incompatibility reactions. How severe is this reaction?
Symptoms and signs of **_acute intravascular haemolysis_** (**IgM-mediated**) - this is **SEVERE/FATAL.**
* **General**:
* restless,
* chest/loin pain,
* fever,
* vomiting,
* flushing,
* collapse,
* haemoglobinuria (later)
* **Monitoring**:
* Low BP,
* High HR,
* High Temperature
44
What are 3 causes of ABO incompatibility reactions?
* Failure of bedside check
* Wrongly labelled blood sample
* Laboratory error
45
What is the management (incl investigations) for acute haemolytic reactions due to ABO incompatibility?
* FBC
* Biochemistry
* Coagulation
* Repeat X-match
* Direct antiglobulin test (DAT)
46
What are the signs and symptoms of bacterial contamination reactions in transfusion? How severe is this reaction?
Presents similarly to ABO mismatch - SEVERE/FATAL
**General**:
* restless,
* fever,
* vomiting,
* flushing,
* collapse
**Monitoring**:
* Low BP,
* High HR,
* High Temperature
47
What is the source of bacterial contamination in blood and what causes this reaction? Which blood components are most likely to be contaminated?
* 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:
* Platelets (_stored at room temperature_) \> RBCs \> FFP
48
List 3 ways in which bacterial contamination of blood can be prevented.
1. **Donor questioning + arm cleaning + diversion of first 20 mL into a pouc**h (used for testing)
2. Management of RBCs:
* Store in a **controlled fridge at 4 degrees**
* Shelf-life: 35 days
* If it is kept out for **\>30 mins it needs to go back in the fridge for 6 hours**
* Complete transfusion should take place within 4.5 hours of leaving the fridge
3. Platelet management:
* Stored at 22 degrees
* Shelf-life: **7 days**
* Screened for bacteria before release
49
Describe the presentation of an anaphylaxis reaction to blood transfusion.
SEVERE/FATAL
Occurs soon after the start of transfusion:
* **Shock** = Drop in BP + Rise in HR
* Very breathless with wheeze
* Often laryngeal and/or facial oedema
50
What is the mechanism of anaphylaxis reaction in blood transfusion? When are these reactions likely to be more severe?
IgE mediated - IgE antibodies in the patient cause mast cell degranulation
Usually not severe, except in the case of **IgA deficiency (common 1 in 600, in 25% anti-IgA antibodies form when exposed from donor, only a minority have a severe reaction)**
51
What is the pathophysiology of TACO? How severe is it? What are 5 clinical features?
Trasnfusion associated cirulatory overload (TACO); moderate/severe/fatal and is **common** (1 in 100,000)
_**Cause**:_ lack of attention to fluid balance, RF such as cardiac impairment, renal impairemnt, hypoalbuminaemia, very young/old.
**_Clinical features:_**
* **CXR (fluid overload)**
* SoB
* Low O2 saturations
* Fluid overload
* High HR
* High BP
* Cardiac failure
52
What is TRALI in blood transfusion reaction? When is it more common(what component)? What are 5 clinical features? What is seen on CXR?
TRALI = transfusion related acute lung injury; looks like ARDS **(more common in FFP or platelet transfusion)**; n**o clinical fluid overload;** SEVERE/FATAL.
* Clinical features:
* SoB
* Low O2 saturations
* Fever
* High HR
* High BP
* **CXR** = bilateral pulmonary infiltrates during/within 6 hours of transfusion due to circulatory overload and other causes
53
What is the mechanism of TRALI?
Mechanism:
* **Anti-WBC** antibodies in donor blood
* These **interact with WBCs in the patient**
* Aggregates WBCs s**tick to pulmonary capillaries** --\> release neutrophil proteolytic enzymes and toxic O2 metabolites --\> lung damage (however, this mechanism is incompletely understood)
54
What is the managemnt of TACO?
Diuretics (immediately responds to these if TACO is the cause, raised JVP initially)
TRALI does NOT resoond to diuretics (no JVP)
55
56
Which DONORS should you use for plasma/platelets? Why?
MALE donors
no pregnancy or previous transfusions, so no HLA/HNA ABs
57
Which delayed reaction is most common? What is the mechanism? When does the reaction to occur?
**Delayed haemolytic transfusion reaction -** caused by Duffy and Kidd antigens and others
## Footnote
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)
This is IgG-mediated so takes 5-10 days
58
What investigations are done for delayed haemolytic transfusion reaction? What is a complication of this? What is the management?
1. Haemolysis Tests:
* High bilirubin
* Low Hb
* High reticulocytes
* Haemoglobinuria over a few days
* **Test U&E** because it can cause **renal failure**
2. Repeat the group and screen and look for **new antibodies** that may have been made against the transfused red cells
NB: *Patients on admission after transfusion will have haematuria/dark urine and Hb will be lower than it was before the transfusion.*
59
What type of antibody are anti-A and anti-B vs anti-Rh, anti-Duffy and anti-Kidd?
Anti-A/B - IgM
Others are IgG
60
What are 3 examples of dealyed infections due to blood transfusion?
Malaria
Viral infections
Variant CJD (Mad Cow Disease)
61
When does CMV occur following blood transfusion in patients? Which patients get CMV negative blood? How do you prevent CMV in blood?
* Very immunosuppressed patients (e.g. stem cell transplant) can get fatal CMV disease
* CMV -ve products are only given to pregnant women and neonates
* **Leucodepletion/irradiation removes CMV in WBCs** (‘washing’ done for IgA deficient patients)
62
When does parvovirus occur following blood transfusion in patients? What are the complications of this infection?
* Affects foetuses and patients with haemolytic anaemias (e.g. sickle cell, hereditary spherocytosis)
* Causes temporary red cell aplasia – *so affects those with RBCs of a shortened life span*
63
How do we prevent CJD in blood?
* NO TEST
* Blood services **exclude transfused patients as donors** as a precaution
64
How soon after transfusion does transfusion associated GvHD occur? How severe is it?
* Rare but **ALWAYS FATAL** (can take weeks to months to come on after transfusion)
65
What is the pathophysiology of transfusion associated GvHD?
* Donor's blood will contain some lymphocytes that are able to divide
* Normally, the patient's immune system will recognises these donor lymphocytes as foreign and destroy them
* In **susceptible patients (very immunosuppressed)**, these lymphocytes are NOT destroyed
* Lymphocytes recognise patient's tissue HLA antigens as foreign and attack (gut, liver, skin and bone marrow)
66
What are the features/complications of transfusion associated GvHD?
* Diarrhoea
* Liver failure
* Skin desquamation
* Bone marrow failure
* **DEATH**
67
How do you prevent transfusion assciated GvHD in patients?
**Prevention**: _irradiate_ blood components for very immunocompromised patients or have _HLA-matched_ components
68
69
When does post-transfusion purpura occur? Which patients are most affected by post-transfusion purpura?
* Appears 7-10 days after transfusion of _blood_ or _platelets_ and 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)
70
What is the management of post-transfusion of blood or platelets?
IVIG
Usually resolves in 1-4 weeks but can cause life-threatening bleeding
Exact mechanism is unkown
71
What are the consequences of immune modulation (delayed reaction post transfusion)?
Possible increased rate of infections post-operatively and increased recurrence of cancer in patients who have blood transfusions however, the evidence is conflicting
72
How much iron is in each unit of blood? What are the consequences? How is it treated?
200-250mg of iron per unit of blood
Damage to liver, heart and endocrine organs.
Requires chelation
73
How do anti-RhD antibodies form in -ve patients?
* By receiving blood transfusions
* In pregnancy (foetal red cells enter the mother's circulation during pregnancy or at delivery)
74
What kind of consequences are there in pregnancy of RhD antibodies?
1. 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
2. In a subsequent pregnancy, if the mother has another RhD-positive foetus, the **antibodies will destroy foetal red cells leading to severe anaemia ± HDN**
Consequences:
* Foetal anaemia (haemolytic)
* Haemolytic disease of the newborn (anaemia, high BR à builds up after birth as not removed by placenta)
75
Which antibodies can cross the placenta?
Only IgG
76
How much should Hb rise per litre of blood?
10g/L increase in Hb
77
How do we prevent haemolytic disease of the newborn? Will there be a problem if the foetus is RhD-ve?
1. **MOTHER: All women have a group and screen at around 12 weeks (booking) and again at 28 weeks**; if there is an antibody against red cell antigens present then levels should be checked (high/rising suggests it is more likely to affect the foetus)
2. **FATHER**: Check if the father has the antigen (and hence whether the baby could inherit it)
3. **FOETUS**: Check ffDNA sample (allows identification of the baby's RhD group) – **if baby is RhD -ve, there’s no problem**; monitor foetus for anaemia (MCA Doppler ultrasound); the baby may need to be delivered early because HDN gets a lot worse in the last few weeks of pregnancy
78
How can the foetus be monitored for anaemia in the presence of anti-RhD antibodies in the mother?
MCA Doppler Ultrasound (NB: because IgG is crossing the placenta)
79
How are intrauterine transfusions done and when?
* The transfusion is done via the umbilical vein
## Footnote
*NB: monitor baby’s Hb and BR for several days after delivery as HDN can get worst; may need exchange transfusion if BR too high or Hb too low (phototherapy can help reduce BR)*
80
If the foetus gets HDN, what is the prognosis for subsequent pregnancies?
Subsequent pregnancies usually fare WORSE
81
What is the best prevention strategy for HDN? When do these not work?
* If an RhD -ve woman of childbearing age needs a blood transfusion, **ALWAYS** give RhD -ve blood
* IM injection of **anti-D immunoglobulin** can be given at times when the mother is at risk of **sensitisation**
* ****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
82
What is the mechanism of anti-D immunoglobulin action?
* 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
83
List 4 different sensitising events for anti-RhD development.
* At delivery if the baby is RhD positive
* Foeto-maternal haemorrhage is likely to occur (and you do NOT know the Rh status of the baby)
* 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
84
What doses of anti-D are given in different events?
* Doses of Anti-D:
* At least 250IU (for events \<20w gestation)
* At least 500IU (for events \>20w gestation)
* *Sometimes a larger does is needed for larger bleeds*
A foeto-maternal haemorrhage test (**Kleihauer test**) done if \>20w gestation and at delivery, to determine if more anti-D is needed than the standard dose if the foetal bleed is large
85
How do you calculate the anti-D necessary to prevent sensitisation from FMH event?
86
Why has RAADP (rotine antenatal anti-D prophylaxis) been introduced?
1% will become anti-D sensitised with no obvious event so anti-D prophylaxis is given to prevent this:
* 1 large dose (1,500IU) at 28w
* 2 smaller doses (500, 500 IU) at 28w and 34w
87
Which other antibodies can cause severe HDN?
Anti-C and anti-kell but usually less severe than anti-D - *Kell causes reticulocytopenia in the foetus as well as haemolysis*
IgG anti-A/B from group O mothers - usually treated with phototherapy
88
89
What is cffDNA testing? When is the earliest it can be done?
Rapid, non-invasive service for prediction of fetal D, C, c, E and K status, **using cell-free foetal DNA in maternal blood** for women who have allo-antibodies - can be done from 11+2 weeks gestation + results available in 10 days
Upon identification, mothers can be **informed and prepared** for further careful monitoring
Also i**dentifies pregnant women who have antigen -ve foetuses** and who therefore are not at danger from HDFN- then no anti-D needed
