Transfusion

Question 1

What blood groups in the ABO system can you be ?

Answer 1

Group A, B, AB or group O

Question 2

Describe what makes a red cell belong to each of the ABO groups ?

Answer 2

• Group A - the red cell membrane carry A substance/A antigen (a carb, protein or sugar) on their surface
• Group B - their red cell membranes carry B substance/antigen
• Group AB - their red cell membranes carry B substance/antigen
• Group O - their red cell membranes do not carry A or B substance/antigens

Question 3

How do antibodies in our immune system arise against A & B antigens & is this normal ?

Answer 3

This is normal that people develop A & B antibodies, depending on their ABO blood group

This occurs because we are born with our ABO blood group & the antigens expressed on our blood cells are recognised as ‘self’ - meaning that anything which expresses the same antigens will also be recognised as self & antibodies will not be produced against these antigens

But some environmental bacteria esp in the gut express antigens that look like substance A & B. Therefore as soon as we are born out gut becomes colonised with bacteria & by about 6 months old our immune systems begin to respond to these bacteria producing antibodies against anything that is not recognised as ‘self’ meaning e.g:

• If someone is group O they dont have antigens A or B so anything expressing A or B will be recognised as none-self & have antibodies produced against it
• A group A person exposed to A & B antigens would produce anti-B antibody. The opposite for Group B people seen.
• A group AB person exposed to A & B antigens from bacteria wouldnt produce any antibodies

Question 4

What type of antibody are ABO antibodies ?

Answer 4

IgM i.e. anti-A antibodiy is an IgM

Question 5

What does binding of IgM antibodies result in ?

Answer 5

Will activate complement resulting in rupture of the cell

Question 6

Describe the inheritance of ABO blood groups & how they result in antigen formation

Answer 6

Thee are 3 main genes you can inherit:

1. A - dominant
2. B - dominant
3. O - silent gene

A & B are co-dominant & are both dominant over O

A&B genes code for enzymes that attach sugar residues to the red cell membrane ==> resulting in A&B antigens. Note O will not code for an enzyme & ==> no antigen produced

Question 7

What blood groups in the Rh blood group can you be & link this to ABO blood grouping

Answer 7

• You can be Rh(D) +ve or Rh(D) -ve (most people are Rh +ve)
• This blood group is independant from ABO grouping so one can be A Rh(D) +ve (shortened to A pos), O pos, O neg etc etc

Question 8

The presence or absence of what makes someone Rh(D) pos or neg ?

Answer 8

Rh(D) protein on the surface of their red cells

Question 9

Do people usually have Rh(D) antibodies in the blood? explain ans.

Answer 9

• No they dont
• This is because no bacteria carry substance on their cells which mimics Rh(D) protein

Question 10

What are the situations in which someone can develop Rh(D) antibodies ?

Answer 10

If someone is Rh(D) -ve & is exposed to red cells which are Rh(D) +ve for example:

• during pregnancy with a Rh(D) +ve foetus & -ve mother
• Or after transfusion with Rh(D) +ve red cells

Question 11

What can happen by exposing someone who is Rh(D) -ve to Rh(D) +ve blood ?

Answer 11

They can have a delayed haemolytic reaction to the transfused cells (more meaning they become sensitised as they develop Rh(D) antibodies) & if subsequent pregnancy (sensitised in same way in preg unless treated) or transfusion then haemolytic reaction can occur

Question 12

Describe the inheritance of Rh(D)

Answer 12

2 genes involved - ‘D’ & ‘d’, D is dominant & if you have D then you are Rh(D) pos.

Question 13

Define agglutination

Answer 13

It is when blood cells clump together (agglutinate)

Question 14

Describe the agglutination phenomenom & what it is used for

Answer 14

• Basically the process that occurs if an antigen is mixed with its corresponding antibody agglutination occurs
• If you add directly agglutinating antibody to red cells in a test tube that carries the antigen, that that antibody attachs to, the antibody will attach to the red cells & cross link the red cells together ==> they will stick together (agglutinate)
• For example addition of anti-A antibody to group A blood cells or anti-B antibody to group B cells will result in agglutination
• However the addition e.g. of anti-A to group B or O group wouldnt result in agglutination (this is who blood grouping is done)

Question 15

How do we know if agglutination has occured ?

Answer 15

Tip the test tube & if red cells not in solution, agglutination has occured

Question 16

What are the 3 reagents which can be added to determine someones ABO blood group?

Answer 16

• Anti-A
• Anti-B
• Anti-A,B - O group pts have an antibody which will bind to A or B hence neeed to use Anti-A,B reagent

Question 17

What is the potential blood groups of the following people shown in the pic

Answer 17

• Patinet 1 could be blood type B or O
• Paitnet 2 could be A or O
• Patient 3 is O
• Patient 4 is B or O
• Patinet 5 is A or O
• Paitnet 6 is +ve any of the main groups

Question 18

What are the main other types of red cell antigens which may be present on their surface ?

Answer 18

• Kell group: K, k
• Duffy group: Fy^a, Fy^b
• Kidd group: JK^a, JK^b

Note - Rh(D) group has subunits C,c & E,e

Question 19

Do we usually need to check patients for these other main blood groups >

Answer 19

No - because their immunogenicity is low so people do not usually develop antibodies against these antigens

Question 20

When do you need to take into consideration these other main red cell antigens ?

Answer 20

• Only when a patient is known to have an antibody to any of these antigens (blood groups) possibly stimulated by a previous pregnancy or transfusion
• If a patient does have an antibody to ≥ 1 of these antigens, the red cells given to them must be -ve for the antigen(s) in question

Question 21

Describe the process for giving a patient a transfusion (dont learn just appreciate)

Answer 21

1. Obtain blood sample from patient - accurate ID is critical so make sure to check patient ID
2. Complete request form:

• patient ID, location, indication for transfusion
• time required, number of units required,
• previous transfusion history, your name (legible)
• and contact number

3. Send sample and form to the transfusion lab (if outwith normal hours, contact the Biomedical Scientist (BMS))
4. Prepare patient for transfusion

Question 22

What happens to the labelled blood sample at the transfusion lab ?

Answer 22

1. They ensure details on sample tube & req form are complete & correct
2. Check patients previous transfusion history
3. Centrifuge sample tube to separate RBC’s & plasma (required for determining blood groups)
4. Determine ABO & Rh(D) blood groups
5. Screen patients plasma for irregular red cell antibodies
6. Select units from blood bank, taking into account results (of ABO, Rh(D) & presence or absence of irregular antibodies)
7. Once shown to be compatible they are labelled with pts details, issued to approproate blood fridge
8. If not required after 24hrs, pt ID labels are revmoed from blood & units are returned to the blood bank

Question 23

Determine this persons blood grouping

Answer 23

• Have antigen A because +ve agglutination with anti-A
• Dont have antigen B, the +ve agglutination with Anti-A, B is off putting but it occurs because anti-A,B can bind to antigen A or B so ==> the reason for +ve agglutination is becaise antigen A is present
• Patient plasma shows +ve when B cells are added ==> plasma has anti-B
• Red cells +ve for Rh(D)
• ==> patient blood group is A pos

Question 24

How is pts blood screened for irregular red cell antibodies i.e. the other blood groups ? & what are the common ones screened for ?

Answer 24

• Anti-D (Rh)
• Anti-K (produced against kell group antigen)
• Anti-c (produced against Rh sub-group)
• Anti-E (produced against Rh sub-group)
• Anti-Fy^a (produced against duffy group)
• Anti-JK^a (produced against kidd group)

Question 25

Describe the process of screening for irregular antibodies ?

Answer 25

We again rely on the agglutination phenomenom: 1. Use group O red cells (to exclude ant influence of anti-A or anti-B antibodies on the agglutination results) 2. Group O red cells taken from 3 donors who have been selected so that between them, they carry all the clinically sig. red cell antigens 3. A drop of red cells is placed in each test tube (one donor to each test tube) 4. A drop of pts plasma (using only pt plasma & not red cells as only concerned about finding out it patient has any antibodies otherwise would be here all day finding out all the insignificant antigens on the pts red blood cells) 5. Mixture incubated to allow chance for antibodies to bind to the red cells 6. Unlike ABO IgM antibodies, irregular antibodies are IgG & cannot cross link red cells directly, so after incubation period the plasma is washed out directly to remove any unbound antibody 7. Anti-human immunoglobulin (which recognises Fc region of human antibody) added to each test tube, if during incubation antibody was bound to the red cells then its addition will result in the red cells being cross-linked agglutinated 8. This technique is called indrect antiglobulin test (IAT) or indirect coombs test Note - coombs test is also done for checking for anti-D

Question 26

What are the key points to remember about a transufsion request ?

Answer 26

* Dont mix up transfusion req, label them at bedside * If irregular antibodies present we must identify their specificty before being sure they red cells are compatable

Question 27

How are red cells prescribed from the blood fridge

Answer 27

Doctor 1. Prescribe the red cells - number of units special, requirements (eg irradiated red cells, CMV-negative red cells), rate of transfusion, accompanying medication. Each unit of red cells should be completely transfused within 4 hours of leaving the blood fridge 2. Ensure the patient has established IV access - if red cells have been out of a blood fridge for more than 30 minutes, they cannot be returned 3. Record the indications for transfusion in the casenotes Nurses: 1. Nursing staff retrieves units from the fridge (one at a time usually) they check its contents expirey date & details on bag 2. Check pts name by asking them & check their pt ID & do pre-transfusion obs - temp, pulse & BP 3. Commence transfusion & observe

Question 28

What are the indications for red cell transfusiosn ?

Answer 28

1. **Anaemia** - consider giving if Hb \< 70g/L (80g/L if cardiac disease) & pt is unstable. If pt is stable then generally wouldn't transfuse, finding & treating the cause it always best 2. **Acute blood loss** - again use Hb \< 70g/L as a threshold & if unstable or likely to lose lots more blood consider transfusion but if stable or planned blood loss & not likely to loose more then they arent likely to need a transfusion 3.

Question 29

Outline the stepwise approach to acute blood loss

Answer 29

1. Arrest bleeding 2. Gain IV access 3. Samples for cross-matching, and other tests 4. Restore and maintain blood volume by giving fluids first e.g. - N saline, albumin, gelofusin 5. ABO and Rh(D), Ab screen and cross-match - 1 hour or Type specific (ABO and Rh(D), immediate spin cross-match – 10- 20 minutes 6. Emergency Group O Rh(D) neg blood (this isn’t compatible for everyone but it’s the best you can do without results of blood groups etc immediately available if really needed 7. Aim at least to maintain normal pulse rate, BP, consciousness, urine output \>30 ml/hr, Hb \> 100 g/L

Question 30

What are the key points regarding platelet transfusions ?

Answer 30

* Platelets are obtained from 4 whole blood cell donations * No cross-match required, but account needs to be taken of donor and recipient ABO and Rh(D) groups * Same pre-transfusion checks as for red cells

Question 31

What conditions should platelets be stored in ?

Answer 31

* NEVER A NORMAL FRIDGE * Can be stored at 22 degrees for 5 days or 20 degrees for 7 days

Question 32

What are the indications for platelet transfusion ?

Answer 32

* Platelet count \< 10x10⁹ for pts who are not bleeding or having invasive procedures/surgery * It pt has fever consider giving platelet transfusion at higher threshold 20-30x10⁹ * \< 50x10⁹ following surgery, if ophthalmic or neurosurgery then platelet count of \< 100x10⁹ transfuse * Prophylaxis in patients with bone marrow failure and very low platelet counts * Treatment of bleeding in thrombocytopenic patient * Prophylaxis prior to surgery/ procedure in thrombocytopenic patient

Question 33

What are the contraindications to platelet transfusion ?

Answer 33

* Autoimmune thrombocytopenia - as platelets will be destroyed * Chronic bone marrow failure * Heparin induced thrombocytopenia * Thrombotic thrombocytopenia purpura

Question 34

What are the storage conditions of Fresh frozen plasma (FFP)?

Answer 34

-30 degrees for 3 years, infuse within 4hrs of thawing

Question 35

What are the compatability requirements for FFP?

Answer 35

Same as for platelets i.e. no cross-match but use from same ABO & Rh(D) status

Question 36

What are the indications for use of FFP?

Answer 36

* Treatment of bleeding in patient with coagulopathy (PT ratio \>1.5) * Prophylaxis prior to surgery or procedure in patient with coagulopathy (PT ratio \>1.5) * Management of massive haemorrhage * Transfuse early in trauma * DIC (disseminated intravascular coagulation)

Question 37

What is DIC ?

Answer 37

* This is where there is widespread activation of coagulation, from release of procagulants into the circulation which causes small blood clots to develop throughout the bloodstream, blocking small blood vessles * This results in consumption of clotting factors & platelets * This may happen due to malignancy, infection/sepsis, ABO mist-matched transfusion or trauma

Question 38

What are the signs/symptoms of DIC?

Answer 38

Signs - Bruising, bleeding anywhere, renal failure

Question 39

What are the blood results suggestive of DIC?

Answer 39

* Increased APTT & PT, d-dimer * Decreased fibrinogen

Question 40

How is DIC treated ?

Answer 40

* Replace platelets if \< 50x10⁹ * Cryoprecipitate to replace fibrinogen * FFP to replace coagulation factors

Question 41

The compatability of plasma for donor to recipient is a bit different explain who can recieve what

Answer 41

* Any antibodies in the plasma being transfused cannot react with the recipients cells so group O can only be given to a group O recipient * But AB plasma can be given to any patient as someone with AB wouldnt have any antibodies so there plasma is ok to give to all

Question 42

List the potential hazards/side effects of transfusions

Answer 42

1. Immediate haemolytic transfusion reaction 2. Delayed haemolytic transfusion reaction 3. Febrile non-haemolytic transfusion reaction 4. Urticarial reactions (hives) - erythema, papules, itch 5. Circulatory overload 6. Bacterial infection 7. Viral infection

Question 43

Describe what immediate haemolytic transfusion reactionss are (ABO or Rh incompatability)

Answer 43

A few irregular antibodies can provoke this reaction but mainly it is caused by ABO incompatable cells: 1. The wrong ABO blood group cells transfused to the pt e.g. Group A transfused to a group O pt 2. As soon as group A red cells enter the circulation, IgM antibodies (e.g. anti-A in this example) bind to the cells corresponding antigen(s), immediately activating the complement cascade, coagulation & kinin systems 3. Complement cascade releases C3a & C5a (increasing vascular permeability & dilating blood vessles) which inturn releases serotonin & histmaine (resulting in fever, chills, shock & hypotension) 4. Formation of membrane attack complex (MAC) which leads to rupture of transfused cells 5. Thromboplastic material released from haemolysed red cells leads to activation of the coagulation cascade ==\> DIC 6. Activated factor XII activates the kinin system reuslting in arteriolar dilatation, increased vascular permability ==\> leading to hypotension, inturn resulting in release of catecholamines which cause vasoconstriction within kidneys & other organs **Essentially you get systemic hypotension, DIC, renal vasoconstriction, formation of renal intravascular thrombi, shock, renal failure ==\> this is often fatal**

Question 44

What are the clinical features of immediate haemolytic transfusion reactions ?

Answer 44

Reaction starts pretty much straight away with features of: * may begin after only 1 ml is transfused * pyrexia / rigors * faintness / dizziness * tachycardia / tachypnoea / hypotension * pallor / sweating * headaches / chest or lumbar pain * local pain at infusion site * cyanosis * patient may say “something is wrong”

Question 45

What do you do if someone develops an immediate haemolytic transfusion reaction ?

Answer 45

Stop transfusion Start IV fluids (combat hypotension) Obtain blood samples: * FBC * Blood film * Coag screen * Serum haptoglobin (this binds to free Hb so likely to be low from being used up) * Renal function (eGFR) * Lactate

Question 46

What do you send back to the transfusion lab if someone develops an immediate haemolytic transfusion reaction ?

Answer 46

Remains of unit given & untransfered units

Question 47

What investigations do the transfusion lab do when someone has an immediate haemolytic transfusion reaction ?

Answer 47

1. ABO and Rh(D) group on pre- and post-transfusion samples, and on transfused and untransfused units 2. DAGT on pre- and post-transfusion red cells determine whether or not transfused or untransfused units are indeed compatible 3. Remains of unit being transfused sent for bacteriological culture (as bacteria is another cause not just ABO incompatability)

Question 48

When do delayed haemolytic transfusion reactions typically occur ?

Answer 48

Haemolysis usually occuring 5-10 days after transfusion

Question 49

What are the clinical features of delayed haemolytic transfusion reactions ?

Answer 49

* Symptoms / signs similar to, but less acute than immediate HTR * Unexplained fall in Hb value as transfused red cells are destroyed * Appearance of jaundice, renal failure or biochemical features associated with IHTRs * Detection of positive DAGT or irregular antibodies in post- transfusion blood samples

Question 50

What is usually the cause of delayed haemolytic tranfusion reactions ?

Answer 50

Irregular antibodies

Question 51

Describe the mechanism of delayed haemoyltic transfusion reactions

Answer 51

Using the example of a pt who is kell -ve, whom is transferred kell +ve red cells: 1. Pt mounts response by making anti-kell antibody 2. Anit-kell binds to kell antigens (most irregular antibodies do not activate complement, so NO intravascular red cell destruction occurs) 3. However when antibody coated red cells go through the spleen, macrophages mount an attack breaking off fragments of the Ab coated red cells, resulting in loss of some of these red cells membranes, however they manage to escape back into the circulation 4. They then repair the damage but in doing so change shape from biconcave to sphere resulting in spherocytes being seen. Damaged cells also release some Hb which is metabolised hence pt may develop jaundice

Question 52

What are the lab results suggestive of a delayed haemolytic transfusion reaction ?

Answer 52

* anaemia, spherocytic red cells on blood film * elevated bilirubin and LDH * positive DAGT and/or appearance of red cell allo-antibody * +/- a degree of renal failure

Question 53

Describe febrile non-haemolytic transfusion reactions, including what will be detectable on investigations & how further ones are prevented

Answer 53

* Developement of Rapid temperature rise 1 - 2^oC, chills, rigors * Antibodies to contaminating white cells release of cytokines and vasoactive substances from white cells during storage * May be difficult to differentiate these symptoms from those of very early acute HTR * Investigation: HLA antibodies may be detectable, no evidence of red cell incompatibility

Question 54

How are febrile non-haemolytic transfusion reactions prevented ?

Answer 54

Anti-pyretics and leucodepleted blood components

Question 55

Describe what a allergic transfusion reactions presents like, what its due to & what is done in the management of it

Answer 55

* Mast cell - IgE response to infused plasma proteins * Can range from urticaria (Rash / weals within few minutes of starting transfusion) to anaphylaxis with hypotension, dyspnoea, wheezing, and stridor, or angioedema. * Simple urticaria Mx = Slow the transfusion & Consider anti-histamines * More severe allergic reaction or anaphylaxis urgent tx = discontinue + IM adrenaline +/- (consider Antihistamine, corticosteroids & bronchodilators)

Question 56

What is transfusion related lung injury (TRALI)?

Answer 56

* TRALI is now the leading cause for transfusion-related mortality. It is caused most often when donor plasma contains HLA or leukocyte (usually granulocyte) specific antibodies. * It is characterised by the development of hypoxaemia / ARDS within 6 hours of transfusion.

Question 57

What are the typical features of TRALI ?

Answer 57

Hypoxaemia / ARDS within 6 hours of transfusion. Features include: * hypoxia * pulmonary infiltrates on chest x-ray * fever * hypotension

Question 58

What do you need to be careful of in transfusing pts with circulatory failure esp HF and esp elderly pts with it ?

Answer 58

* Circulatory overload & Pulmonary oedema * As well as features of pulmonary oedema the patient may also by hypertensive, a key difference from patients with TRALI. * Reduce or stop transfusion (note max time can only be upto 4hrs) & give furosemide

Question 59

What are the features of bacterial infection from a transfusion?

Answer 59

May present very similar to an immediate haemolytic transfusion reaction: * Fever * immediate collapse * shock * DIC * Fever, chills, vomiting, tachycardia, hypotension

Question 60

What is the management of bacterial infection caused by transfusion?

Answer 60

1. The same as the management of an immediate haemolytic transfusion reaction 2. Once the laboratory has proved that your patient has NOT HAD an ABO-incompatible transfusion, you will want to start broad-spectrum IV antibiotics pending identification of the offending bacteria

Question 61

What are some of the other potential transfusion complications ?

Answer 61

* Hyperkalaemia * Iron overload * Clotting

Question 62

What are the risk of HIV, Hep B or C being transmitted via transfusion?

Answer 62

* HIV 1 per 6 million units transfused * HBV 1 per 1.6 million units transfused * HCV 1 per 26 million units transfused

Question 63

What conditions should red blood cells be stored at ?

Answer 63

4 degrees +/- 2 degrees with a shelf life of 35 days

Question 64

What observations are required when a pt is having a transfusion?

Answer 64

* •Observations before blood is commenced * •Observations at 15 minutes * •Observations within 60 minutes of completion