Haematology 14 - Blood Transfusion 1 & 2 Flashcards
What is the importance of RhD negative RBC?
What happens if you give RhD+ blood to RhD- people?
These are safe to give to everyone but are often in short supply
If you give RhD+ blood to RhD- patients doesn’t cause an acute disaster but can induce the formation of anti-D antibodies
Next time person is transfused it must be with RhD- blood because if you give Rhd+ blood again it will cause haemolytic disease
What does a group and screen consist of?
Group: blood group testing using forward and reverse group- Test patient’s ABO and RhD group
Screen: screening the patient’s plasma for potential antibodies against RBC that will be transfused
Recall 2 ways in which patients’ blood group is tested
- Forward group (to figure out which antigens are on patient’s RBC): Using anti-A,B, D and O reagents against the patient’s red blood cells
- Also use ‘reverse group’ - known A and B group RBCs against the patient’s plasma. If patient is positive for anti-A, it means they are B-positive (hence “reverse”).
Describe the process of antibody testing of blood
- Use 2 or 3 reagent red blood cells containing all the important RBC antigens between them
- Then incubate the patient’s plasma using the indirect antiglobulin technique
*if there are visible agglutination/clumps forming then antibodies are present in patient’s plasma
What are the two types of cross match?
1) Electronic cross-match:
Compatibility determined by IT system rather than manually. Done in emergency situations
2) Serological cross match (see picture)
a) Full cross match - uses IAT
b) immediate spin - quicker technique - used in emergencies
What is the purpose of ‘immediate spin’ blood testing?
Used in emergencies only
Incubation for just 5 minutes
Determines ABO compatibility only
What are the 3 pillars of patient blood management?
- Optomise haematopoiesis- treatment of anaemia
- Reduce bleeding (eg stop anti-platelt drugs, cell-salvage techniques)
- Harness and optomise physiological tolerance of anaemia
For which blood products is D compatibility required?
Red cells and platelets (but not FFP or cryoprecipitate)
*for all they need to be ABO compatible
*also for FFP and crypprecipiatte you don’t need to do cross match
Who is the universal donor for platelet transfusions?
Group A!!
Not group O like for RBC!
What is the storage temperature of red cells, platelets, FFP and cryoprecipitate?
Red cells: 4 degrees C (fridge)
Platelets: 20 degrees C (room temperature) >>> more likely to be contaminated
FFP: 4 degrees C once thawed
Cryoprecipitate: Room temp once thawed
Red cells and FFP: fridge
Platelets and cryoprecipitate: room temperature
What is the storage length of red cells, platelets, FFP and cryoprecipitate?
Red cells: 35 days
Platelets: 7 days
FFP: 24 hours
Cryoprecipitate: 4 hours
What is the transfusion rate of red cells, platelets, FFP and cryoprecipitate?
Red cells: 1 unit over 2-3 hours
Platelets: 1 unit over 20-30 mins
FFP: 1 unit over 20-30 mins
Cryoprecipitate: 1 unit over 20-30 mins
What is the trigger for transfusion in these situations?
1) major blood loss: >30% blood volume lost
2) peri-operative: Hb<70 or 80 depending on comorbidities
3) post chemo: hb <80
**also consider symptomatic anaemia- IHD, breathless, ECG changes
How much does 1 unit of RBC transfusion equate to in g/L in the average 70.80 kg man?
1 unit = 10g/L
How much blood loss counts as ‘major’?
>30% blood volume lost
When are platelets contra-indicated?
-
Thrombotic thrombocytopaenic purpura (TTP)
- unfractionated heparin rather than LWMH
-
Heparin-induced thrombocytopaenia and thrombosis (HiTT)
- Platelets block up the microcirculation so giving platelets will aggravate this
Giving platelets gives the condition worse
What are the indications for FFP transfusion?
1) Massive transfusion
2) Liver disease - only if PT<1.5
3) Single coagulation factor deficiencies eg factor V
4) TTP - to replace ADAMS enzyme (special type of FFP)
5) DIC in the presence of bleeding and other abnormal features
: all the coagulation factors and platelets are removed from the cell intaoperative/post operative cell salvage blood so need to give FFP
What does cryoprecipitate contain?
In which situations can you get your own blood?
Intraoperative or perioperative cell salvage
but NOT for pre-operative autologous deposit as no net benefit- also not done in the UL
: all the coagulation factors and platelets are removed from the intraopeative and post operative cell salvage blood so need to give FFP
Cell salvage is useful in people with RARE blood groups and Jehovah’s witnesses
In what type of surgery is post-operative cell salvage most often done?
Knee surgery
- Collect blood that is lost post-operatively into a wound drain
- Mainly done for orthopaedic operations (e.g. knee surgery)
What are the steps of intra-operative cell salvage?
Centrifuge, filter, wash before re-infusing blood
*ie collect blood lost during operation and give it back to pt
What special blood reuquirements do pregnant women have?
CMV neg
What special blood reuquirements do highly immunocompromised patients have?
patients cannot destroy incoming donor lymphocytes
Blood needs to be irradiated in order to avoid fatal transfusion associated graft v s host disease
**irradiation is different to leukodepletion (blood is leukodepleted by default)
What special blood requirements do patients who have had severe allergic reactions in the past to transfusion have?
Washed cells (RBC and platelets)
also seen in IgA deficient patients
Recall the 10 classes of transfusion reaction, and which are acute/ delayed?
Acute (<24 hours):
- Acute haemolytic (ABO incompatible)
- Allergic/ anaphylaxis
- Bacterial infection >> occurs typically with platelets
- Febrile non-haemolytic
- TACO/TRALI (TRALI is more rare than TACO)
- TACO common in patients with pre-existing cardiorespiratory conditions >> so may already be fluid overloaded
- these patients should have prophylactic diuretics
- main distinguished between TRALI and TACO = BP
Delayed (>24h):
6. Delayed haemolytic transfusion reaction (antibodies) = 7-10 days after
- anaemia + dark urine + jaundice
- Transfusion-associated GVHD: 2 weeks post-transfusion
- Infection (viral, malaria, CJD)
- Post-transfusion purpura
- Iron overload (thalasaemia patients mostly)
What monitoring should be done during a blood transfusion as minimum?
- Baseline temp, HR, RR, BP BEFORE TRANSFUSION
- Repeat obs after every 15 mins - most reactions start within 15 mins
- Repeat hourly after end of transfusion- some reactions start after end of transfusion
Many acute reactions start as:
- Rise in temperature or pulse
- Fall in BP
- This can occur before the patient feels symptoms
What are the features of febrile non-haemolytic transfusion reaction? + cause
WHat severity is this?
Temp increase <1 degree - Low fever
Chills and rigors
*NO CIRCULATORY COLLAPSE*
*caused by release of cytokines in donor which cause a reaction*
*in a qs- might be someone who feels v feverish but when you go to measure the temp it’s not that high*
*mild-moderate severity
Why is febrile non-haemolytic transfusion reaction rare nowadays?
Blood is now leucodepleted to reduce risk of febrile non-haemolytic transfusion reaction
How should febrile non-haemolytic transfusion reaction be managed?
Stop/ slow the transfusion and give paracetamol
What is the pathophysiology of febrile non-haemolytic transfusion reaction?
Cytokines released by white blood cells during storage cause a febrile reaction upon transfusion
Allergic transfusion reactions:
- Sx
- Management:
- Cause. +risk factors (2)
Severity: mild/moderate
Sx: : urticarial rash, wheeze,
Management:
- Stop/ slow transfusion
- IV antihitamines
Cause:
- allergy to plasma protein (more common with plasma than blood products) so may not recur if they receive diff product
- more common if other allergies/atopy present
What are the symptoms of ABO incompatibility?
- May occur 1-2 hours post-transfusion
acute intravascular haemolysis (IgM-mediated)
- Shock:Low BP and high HR (shock)
- high grade fever- unlike febrile non haemolytic transfusion reaction
- Restlessness, vomiting and collapse
- Flushing
**also this is the only transfusion reaction that is associated with pain - particualrly in abdomen, chest, loin or back
**NB does not present with breathlessness**- this is seen in anaphylaxis reactoin
What is the appropriate management for ABO incompatibility?
how can it be prevented
Stop transfusion
Check patient and component
Repeat bloods:
- FBC
- Biochemistry
- Coagulation
- Repeat crossmatch
- Direct antiglobulin test (DAT)>>> would be POSITIVE
Contact senior haemoatologists
prevention:
- adequate of bedside check
- correctly labelled and handwritten blood sample
- avoid Laboratory error
What are the symptoms of bacterial contamination of blood?
Presents very similar to wrong blood (ABO mismatch) - shock, increased temp, restless, fever, vomiting, collapse
How does bacterial contamination of blood cause symptoms? and which products have highest risk of contamination
Bacterial growth –> endotoxin which causes immediate collapse
bacteria could have come from the donor
bacteria could have been introduced during processing
order of liklihood in products:
- Platelets (stored at room temperature)
- RBCs
- FFP
Recall some protocols for prevention of bacterial contamination of blood
Donor questionning
Arm cleaning
Diversion of first 20mls of blood for testing
Proper storage
With ALL components, look for abnormalities such as clumps of discoloured debris, brown plasma etc.
RBCs:
- Store in a controlled fridge at 4oC (+/- 2oC)
- Shelf life: 35 days
- If it is kept out for 30 minutes, it needs to go back in the fridge for 6 hours. This is to help reduce the risk of bacteria growing.
- Complete transfusions should take place within 4.5 hours of leaving the fridge
Platelets:
- Stored at 22oC- Room temperature (+/- 2oC)
- Shelf life: 7 days (if had bacterial testing (BacT), otherwise 5 days)
- Screened for bacteria before release
- Transfuse across 20 minutes
Presentation of anaphylaxtic reaction + mechanism of action
mechanism of action: IgE antibodies in the patient cause mast cell degranulation and release of vasoactive substances
presentation
- soon after the start of transfusion
- Very similar to ABO incompatibility
- shock + collapse + hypotension + tachycarida
- Often laryngeal and/or facial oedema
- wheeze + breathlessness (this is what differentiates this from ABO incompatibility)
Which patients are at most risk of anaphylactic reaction to a blood transfusion?
Those with IgA deficiency - tend to have more severe reaactions
anti-IgA antibodies develop in response to exposure to IgA in the donor blood (transfusion especially with plasma)
Among the respiratory complciations of transfusions which are the most and least common?
TACO- most common especially in those with pre-exisitng cardiorespiratory pathology >> they should be given prophylactic diuretics
Followed by TAD- transfusion associated dyspnoea
TRALI- is the rarest
*r for RARE
How quickly does TACO/TRALI present?
Within 6 hours
What does TACO stand for?
Transfusion-associated circulatory overload
What are the symptons of TACO?
Severity?
pulmonary oedema/ fluid overload
- SOB, decreased SaO2
- increased HR and BP (due to pulmonary oedema)
CXR looks like that for pulmonary oedema: fluid overlaod and cardiac failure
Severity: mild, moderate or severe
What should be checked pre-transfusion to reduce the risk of TACO?
and what are risk factors for TACO
Check the patient is not always in positive fluid balance
Check they don’t have risk factors for TACO - if they do, they need a aprophylactic diuretic
Risk factors - previous cardiac history, renal impairment, hypoalbuminemia, very young/ old)
What is the probably cause of TRALI?
Severity?
How does it present? + CXR findings
mechanism: Anti-WBC (HLA or neutrophil) antibodies in donor blood >> Aggregates of WBCs get stuck to pulmonary capillaries >>> release of neutrophil proteolytic enzymes and toxic O2 metabolites >>> lung damage
Seveirty: severe or fatal
Presents with SOB, low oxygen saturations, bilateral pulmonary infiltrates, tachycardia and HYPOTENSION (unlike hypertension in TACO)
-
CXR
- Bilateral pulmonary infiltrates during/ within 6 hours of transfusion due to circulatory overload and other causes
What is the main difference in the management of TACO and TRALI?
in TACO the JVP is elevated so will respond to diuretics- furosemide
Unlike TRALI which will not respond to diuretics
TACO is more common than TRALI
TACO presents with hypertension and TRALI presents with hypotension
Transfusion assoictaed infections
- when does it present?
- examples
- how do we prevent transfusion associated infections?
- type of delayed transfusion reaction
- symptoms present months-years later
- examples: malaria, viruses (eg parvovirus,) vCJD
- Prevention:
a) Routinely checked: HIV1, HepBCE, HTLV1, syphyllis (and then others depending on travel history)
b) CMV negative blood reserved for pregnant women
What is the pathophysiology of delayed haemolytic transfusion reaction?
How common is this?
Stage 1: Development of an ‘immune’ antibody to a RBC antigen they lack (‘allo-immunisation’)
Stage 2: Transfused with RBC containing this antigen–>mount an immune response >>> extravascular haemolysis
IgG mediated so takes 5-10 days
**very common transfusion reaction
Over what time period does delayed haemolytic transfusion reaction develop?
5-10 days
IgG mediated so takes 5-10 days
Recall clinical features of delayed haemolytic transfusion reaction and what Ivx should be done
Severity?
- DAT positive
- Jaundiced- raised unocnjugated bilirubin
- low Hb
- raised LDH and reticulocytes
- extravascular haemolysis
Haemoglobinuria- dark urine due to haemolysis
Test U&E because it can cause renal failure
* severity = mild/moderate
What is the prognosis of transfusion-associated GVHD?
Always fatal
Which patients are most at risk of transfusion-associated GVHD?
Severely immunosuppressed
What is the cause of transfusion-associated GVHD?
Normally donor blood contains some lymphocytes, which are destroeyd by the recipient’s immune system
However if someone is immunocopmorised they don’t destroy the lymphocytes and they persist,recognising tissue as foreign –> damage to gut, liver, skin etc.
***in GVHD, patient would be given blood from ABO or rhesus compatible donor, but the issue is HLA incomaptibility***
How can transfusion-associated GVHD be prevented?
Irradiate blood for immunosuppressed patients OR have HLA-matched components
This destroys potential lymphocytes in the blood
What are the symptoms of transfusion-associated GVHD?
Severe diarrhoea
Liver failure
Skin desquamation
Bone marrow failure
- DEATH – weeks to months after transfusion
How long after a transfusion do post-transfusion purpura present?
- Appears 7-10 days after transfusion of blood or platelets
What is the pathophysiology of post transfusion purpura and who does it affect?
who does it typically affect
Affects HPA-1a negative patients
Who have been previously immuninsied by pregnancy or transfusion–>giving rise to HPA-1a antibodies >> HPA= human platelet antigen
And during being transfused these antibodies attack own platelets??
Exact mechanism unknown
- HPA= human platelet antigen
How should post-transfusion purpura be treated? + presentation
- Get very low platelet counts (<20x109/L)
treatment: IV Ig
What is the main complication risk of post-transfusion purpura?
Big life-threatening bleeding
How can iron overload be prevented?
iron overload presentation
iron chelators (e.g. exjade/Deferoxamine) with transfusions once ferritin > 1000
cardiac- cardiomyopathy
testes- infertility
pancreas- bronze diabetes
skin- pigmentation
When are pregnant women checked for RBC Immunoglobins during pregnancy, to prevent HDFN?
12 and 28w gestation
*booking visit (8-12 weeks) and then at 28 weeks
If a pregnant woman has RBC antibodies that put the baby at risk of HDN, what should be done?
- Check if the father has the antigen >>> hence the baby could inherit it
- Monitor the level of antibody >>> (high/ rising suggests it is more likely to affect the foetus)
- Check ffDNA- cell free foetal DNA- sample > allows identification of the baby’s RhD group
- Monitor foetus for anaemia > MCA doppler USS
- Deliver baby early >> haemolytic disease of the newborn gets a lot worse in the last few weeks of pregnancy
- Sometimes, IU transfusions may be needed if the baby is VERY anaemic via the umbilical vein
What is the anti-D dosing during pregnancy?
how do you determine dosing
250 IU- for events < 20 weeks gestation
At least 500 IU- for events > 20 weeks gestation (including delivery)
A foetomaternal haemorrhage test (Kleihauer test) is done if > 20 weeks gestation and at delivery, to determine if more anti-D is needed than the standard dose, if foetal bleed is large.
How does anti-D work during pregnancy to prevent haemolytic disease of the newborn?
RhD pos foetal cells get covered in anti-D Ig
Mother’s reticulo-endothelial system removes coated cells (spleen) before they get chance to sensitise mother to produce anti-D antibodies
How quickly must anti-D be given following sensitisation events?
anti-D injection must be given WITHIN 72 HOURS of the sensitising agent
can do it within 10 days but less effective
does NOT work if the mother has already been sensitised and developed anti-D in the past.
Recall some examples of sensitising events
sensitising events during pregnancy where foetomaternal haemorrhage is likely to occur (and you do NOT know the Rhesus status of the baby:
- spontaneous miscarriages if surgical evacuation needed and therapeutic terminations
- Amniocentesis/ CVS
- Abdominal trauma
- External cephalic version
- Still birth / IU death
at delivery- if baby is RhD positive
What is the routine anti-D prophylaxis for mother’s with no obvious sensitising events?
routine anti-D prophylaxis can be given in the 3rd trimester
1500 IU anti-D Ig at 28-30 weeks
O positive vs O negative: which one is universal donor and which one is used when?
O positive is safe to give in emergencies to males and women over 50 or not childbearing age
O negative is reserved for specific indications as it is scarce in supply
Features of haemolytic disease of the newborn
What electrolyte abnormalities can be seen following RBC transfusion?
Hyperkalaemia
Hypocalcaemia
What are the thresholds for platelet transfusions in different groups of people?
Normally: <30 x 10^9 with clinically significant bleeding
If severe bleeding: <100x10^9
If bleeding in critical sites eg CNS: <90 x 10^9
Transfusion of which blood product is at highest risk of bacterial contamination?
Platelet transfusions because platelets are stored at room temperature
Non haemoluyic
*temp doesn’t go up by that much
*HR and BP trend is fine - it’s not going in tachycardia/hypotension directino*
Haemolytic transfuison reaction
happens v quickly
tend to get abdominal pain with haemolysis- not sure why
Summarise the timeline of transfusion reactions
Which patients are particularly susceptible to anaphylactic reaction?
Those with IgA deficiency
Because this means they may have antibodies against IgA
Anaphylaxis vs ABO incomaptibility vs bacterial contamination
TACO vs TRALI vs febrile non haemolytic transfusion reaction
normal JVP: 3-4 cm
Delayed haemolytic reaction vs GvHD
Most common way to prevent gVHD
irradiated blood products
Universal donor for FFP
Group AB negative
*bc they won’t have any anti-A or anti-B antibodies*
Indicatiosn for transfusion of RBC, platelets and FFP
which transfusion reaction causes a rash?
allergic reactions
delayed haemolytic transfusion reactions
Main difference between haemolytic transufsion reatcion and febrile non-=haemolytic transfusion reaction
In febrile non=haemolytic, blood pressure is not affected whereas in haemolytic transfusion reaction you get hypotension because RBC are being attacked
Do febrile non-haemolytic transfusion reatcions happen in the context of compatible or incomaptible donors?
**from older yr: A lady with several children already is having another child, and requires a blood transfusion following blood loss in/during/after pregnancy. But during the transfusion there is some sort of reaction.”- what could this be?
happens in the context of compatible donors
Answer: febrile non-haemolytic transfusion reaction because it is occuring in the context of a compatible transfusion
indications for platelet transfusions
- platelet levels stay at the baseline or goes down after platelet transfusion what does this mean
platelet antibodies being made
what does FFP contian
- Contains ALL the clotting factors
- treatment of choice to reverse warfarin
- PCC (Prothrombin complex concentrate) – this contains factors 2, 7, 9, 10
what should you make sure to do once youve got patients blood in a bottle
Make sure you HANDWRITE the bottle- all the patient’s details at the BEDSIDE
QUESTION: If a blood group O patient was transfused group A RhD negative red cells, what type of transfusion reaction would occur?
- Acute intravascular haemolytic transfusion reaction- IgM Mediated ABO incompatibility
Group and Save is valid for how long in those who have recieved a recent blood transfusion and havent
- 3 months in a patient who has not previously received a blood transfusion
- If a patient has received a transfusion, it is normally only valid for 72 hours
how can TRALI be prevented
- This can be prevented by using male donors for plasma and platelets (who haven’t been pregnant (obviously) and have not had any previous blood transfusions) because they will not have antibodies against HLA.
cell-free foetal DNA in maternal blood
Anti D routine in UK
examples of patients that need irradiated blood ?
immunodeficient patients eg those with lymphoma!!
