Blood Products and Transfusion

• ABCDE and get some big bilateral IV or IO access
• Call for help - you're going to need more hands
• 100% oxygen - to fill up the remaining haemoglobin while you fix things
• Call 2222 and put out Major Haemorrhage call
• Fluid bolus of 250-500ml warm crystalloid while waiting for blood, to maintain a perfusing blood pressure (but don't push the BP above 100-120 systolic)
• Tranexamic acid 1g IV
• Keep the patient warm
• Take an arterial blood gas for a baseline Hb, calcium and lactate
• Get calcium ready (gluconate or chloride) to give once you're infusing red cells - aim to give around 1g per 6 units of PRC targetting ionised Ca of >1 mmol/litre
• Give RBC, FFP and Platelets according to your Trust's protocol
• If you don't know what this is then give 1:1:1:1 PRC:FFP:Platelets:Cryo if you can
• When you get a minute, send of FBC, INR, Clotting, Fibrinogen, U+E
• Use TEG/ROTEM if you have it

• Detect and treat preoperative anaemia well before surgery
• Minimise blood loss before, during and after surgery
• Physiological optimisation to enable the patient to cope with blood loss
• Coordinate medical, surgical and anaesthetics teams so everyone is on the same page

• A condition wherein the quantity of erythrocytes and their resulting oxygen carrying capacity is insufficient to meed the body's physiological requirements
• Usually defined as Hb <130 g/L in men and <120 g/L in women
• It can be microcytic, normocytic or macrocytic, or a combination of these depending on the cause(s) of the problem

• Depletion of total iron stores in the body
• Chronic blood loss
• Malmetabolism of iron in specific disease states such as inflammation and malignancy

• Trauma
• Haemophilia
• Menorrhagia
• Family history of bleeding problems
• Anticoagulants
• Liver disease

Google it.

Seriously - patients are on all sorts of new anticoagulants and antiplatelets and the guidance changes - so having a quick look at the latest guidelines is never a bad idea, just make sure you're using a reputable source.

• There are increasing numbers of patients that are taking anticoagulants or antiplatelets (or both) throughout the perioperative period, for all sorts of indications
• There's no blanket rule, but clopidogrel and aspirin are generally stopped 5-7 days before elective surgery
• DOACs are stopped between 2-5 days before surgery depending on the drug and the patient's renal function

If you're struggling for words in an exam, 'An individualised assessment of thrombotic risk in discussion with haematology' is never a bad shout.

• Laparoscopic surgery
• Robot assisted surgery
• Endovascular technique
• Topical haemostatic agents

You often also get marks for 'meticulous technique' and 'senior surgeon' so they're worth mentioning.

• Regional anaesthesia (particularly in orthopaedics and obstetrics)
• Tranexamic acid
• Maintain haemostasis with particular attention to:
• Hypothermia (core temperature above 35°C)
• Acidosis (pH >7.2)
• Hypocalcaemia (aim >1mmol/litre ionised calcium)
• Optimise blood pressure - enough to perfuse the brain, but not too much to worsen bleeding*
• Patient positioning - ensuring good venous drainage from the operative site will reduce avoidable bleeding
• Smooth and calm team leadership, coordinating cell salvage and transfusion efforts

*If you're asked for specific examples of manipulating blood pressure, you can mention hypotensive anaesthesia for ENT or Spinal surgery, and reduction of central venous pressure for liver resection.

Examples of this include your medical bleeders - (peptic ulcers and varices) - and your post-operative bleeders - (haematomas, abdominal drains etc)

Lots of big important studies have come to the conclusion that a restrictive transfusion threshold is safe and sensible - so we end up using the arbitrary number of 70 g/L most of the time.

• Only give what you need, don't reflexively give two units of red cells at a time just because 'that's what we normally do'
• Aim for 70 in normal patients, and 80-90 in those with cardiovascular disease

If they're symptomatic, and have lost a lot of blood, but have an Hb slightly above the transfusion threshold, then transfuse them now - it's likely their Hb will drop below 70 by 3am.

Ignore their haemoglobin, and treat the patient using your clinical acumen and - more importantly - common sense.

• If a patient loses two litres of blood in ten minutes and you test their haemoglobin - it will still be normal, because the remaining blood hasn't had a chance to dilute yet
• If the patient is clearly in a state of cardiovascular compromise as a result of significant and active blood loss, (tachycardic, poor sats trace, hypotension) then you need to activate the major haemorrhage protocol, because you don't know how long this bleeding is going to continue
• By all means give a bolus of crystalloid while waiting for blood, but do not delay transfusion

It is considerably more preferable to have activated the MHP and not need it, than vice versa.

After all, the MHP has an unused item returns policy that would make ASOS proud.

• Stored at 4°C to inhibit bacterial growth and reduce RBC energy consumption
• Stored in one of two dedicated solutions - SAGM or CPDA1

SAGM - Saline, adenine, glucose and mannitol

CPDA1 - citrate, phosphate, dextrose and adenine

• Citrate chelates calcium and prevents clotting
• Phosphate is a buffer

Packed red cells can be stored for up to 35 days, however there will be gradual deterioration over time:

• Only 70% of the red cells will survive that long
• Haemolysis
• Hyperkalaemia
• Acidosis
• Loss of 2,3-DPG

Group O is the universal donor, and Group AB is the universal recipient, all others need matching up.

• Plasma from one donor
• 150ml bag full of clotting factors, albumin and gamma globulin
• Stored frozen at -20°C and needs to be used immediately once thawed
• Needs to be ABO compatible*
• Dose is 10-15ml/kg (four packs for an average adult)

When to give:

• INR >1.5 and requiring some sort of invasive procedure or actively bleeding
• Pre-emptively as part of major haemorrhage protocol

*Remember that the donor/recipient system is the other way round for FFP, because the donor plasma contains the antibodies rather than the antigens so AB FFP is the universal donor.

• FFP is thawed out slowly, and the precipitate is skimmed off
• Stored at –30^oC for up to a year
• Cryo contains higher levels of factor 8, VWF and Fibrinogen than FFP
• One unit is about 30ml
• Needs to be ABO compatible

When to give:

• If fibrinogen less than 0.8 g/L
• If fibrinogen <1.0 and actively bleeding
• Pre-emptively as part of massive transfusion protocol
• Disseminated intravascular coagulation
• Hereditary hypofibrinogenemia
• Haemophilia
• Von Willebrand disease

Ten units of cryo will raise fibrinogen by 1 g/L

• See below

• e.g. Beriplex
• Contains clotting factors 2, 7, 9 and 10
• Contains protein C and S

When to give:

• For immediate reversal of raised INR in bleeding patient on warfarin
• Warfarin overdose with risk of life threatening bleeding
• When all else fails (chat to Haematology first)

In a patient that is not bleeding

• Platelets less than 10
• Platelets less than 20 if septic or coagulopathic

In a patient who is bleeding, or having a procedure done

• Platelets less than 50
• Platelets less than 80 if needing neuro or eye surgery
• Recent antiplatelet administration or known platelet dysfunction

• Hyperkalaemia - increase in potassium by around 5-10 mmol per unit, however this doesn't usually present a clinical problem as the Na/K ATPases crank this all back into the red cells once they're warmed up inside the patient
• Acid and Alkali - A unit of red blood cells contains up to 2mmol of acid, (citric acid from the anticoagulant and lactic acid from the red cells). Citrate is metabolised to bicarbonate in the liver, which can cause a metabolic acidosis if lots of red cells are transfused

• If you're anticipating blood loss greater than 1000ml, consider using it
• Uses a double lumen suction catheter to collect blood from surgical site
• It then cleans and centrifuges the blood to separate out the components
• The red blood cells are stored ready for infusion back into the patient

Unsurprisingly, it is generally recommended to use tranexamic acid if you've got cell salvage under way.

Here's our full post on cell salvage

• Tranexamic Acid
• ε-aminocaproic acid

These are lysine analogues that inhibit fibrinolysis by targeting plasminogen, preventing the production of active plasmin.

Go check out the CRASH-2 trial at some point.

These point of care tests have been game changers for haemorrhage management.

Check out our full post on TEG and ROTEM here

The main points:

• Point of care testing reduces transfusion requirements
• They're particularly good for assessing fibrinogen levels

• Antibodies in patient's plasma react to surface antigens on the donor red blood cells leading to RBC destruction and haemolysis
• Usually there is previous exposure, either transfusion or placental transfer
• Mostly due to ABO and Rhesus D incompatibility
• There are over 250 red cell antigens that could cause this
• The most serious are anti-A and anti-B
• IgM or IgG are usual culprits

Signs and symptoms:

• Headache
• Chest pain
• Flank pain
• Fever
• Flushing
• Chills and rigors
• Nausea and vomiting
• Urticaria
• Dyspnoea
• Hypotension
• Haemoglobinuria
• Disseminated intravascular coagulopathy

Clearly some of these are harder to spot in an anaesthetisted patient, so a sudden drop in blood pressure may be your first indication.

• Very common
• Usually nothing to worry about
• Caused by donor leucocyte antigens reacting to patient plasma antibodies
• They form a leucocyte antigen-antibody complex
• This complex binds complement
• This results in release of Interleukin-1, IL-6 and TNFα
• Usually kicks in during or a few hours after the transfusion
• Severity is related to speed of transfusion and quantity of leucocytes

Reactions are much less common than they used to be, as pretty much all transfusions are leucodepleted these days.

A direct antiglobulin test will tell you if it's a haemolytic reaction or not.

• This will be negative in the case of a febrile reaction as there won't be any plasma antibodies attached to the donor red cells

Allergic reactions are weirdly common in blood transfusions.

• Donor plasma contains foreign proteins which cause mild IgE mediated reactions
• Usually this manifests as itching or a rash, without substantial cardiorespiratory compromise
• Thankfully anaphylaxis is rare

The best thing to do is usually to stop the transfusion, give an antihistamine such as chlorphenamine, and then if the patient is well in thirty minutes or so, the transfusion can slowly continue.

If they react again then the transfusion should be abandoned.

• Patients with a hereditary IgA deficiency and anti-IgA antibodies are at particular risk of anaphylaxis
• These patients should receive washed PRC transfusions, as these have any residual plasma removed

This is classic exam fodder so it pays to know it in a decent amount of detail.

TRALI has two mechanisms

• immune
• non-immune

Immune is due to white cell antibodies in the donor plasma, targeting HLA (Human leucocyte antigens) and HNA (Human neutrophil alloantigens) in the recipient.

• In around 40% of cases, no antibodies are found, and so it's thought that a reaction is triggered by release of membrane lipids from the donor cells
• In either case the main culprit is the neutrophil granulocyte

These get stuck in the pulmonary microvessels and then release free radicals and enzymes causing destruction of the endothelium

• 70% of patients end up needing mechanical ventilation
• 6–9% of cases are fatal

A definitive diagnosis requires antibody detection

• TRALI can be in response to whole blood, PRC, Platelets or FFP
• Thought to be between 1:1000 to 1:5000 transfusions

• Hypothermia
• Hypocalcaemia and citrate toxicity
• Air embolism
• Hypomagnesaemia
• Acidosis
• Hyperkalaemia

• Caused by physical trauma to red cells, rather than an immune response
• Can cause clinically detectable jaundice

These are thankfully rare nowadays as a result of vigilant screening processes and leucodepletion of blood products, but they're still possible, and still examinable.

As with any question about infections, break it down into the following categories:

Bacteria

• Uncommon but associated with high mortality fulminant sepsis
• Can occur due to contamination from venepuncture, or from a bacteraemic donor
• Packed red cells are stored at 4°C, making infection with gram-negatives such as Yersinia and Pseudomonas more likely
• Gram-positives such as S. Aureus and Bacillus don't enjoy the cold and are more commonly associated with platelet contamination
• Don't transfuse a bag of blood that looks darker than usual or has gas bubbles

Viruses

• Much lower infection rate since better screening of donors
• Donor blood is screened for Hep B, Hep C, HIV 1 and 2, CMV and syphilis
• Infection is still possible if infection not detected by screening due to timing of testing and inoculation

Risk of infection from a single unit of packed red cells:

• Hep B = 1/100 000
• Hep C = 1/1 000 000
• HIV = 1/4 000 000
• Hep A = essentially zero

Prions

• Theoretically possible to transfer CJD prion disease through blood transfusion
• To avoid this, blood is leucodepleted as standard, and people who received transfusions before 1980 are not allowed to donate blood

Terrifyingly there is currently no test or treatment for CJD, so that's fun.

• Essentially the same problem as giving too much fluid to someone with heart failure
• Patient can develop pulmonary oedema and acute heart failure
• Often difficult to distinguish from TRALI

These are usually due to incompatibility between the more minor blood group subtypes such as Kidd and Rhesus.

• The antibodies can get missed during the antibody screening process because of their very low levels, but these then increase dramatically upon exposure to the antigen - this is called an anamnestic response
• This type of reaction doesn't trigger the complement system, meaning there is extravascular haemolysis via IgG, rather than intravascular

Delayed haemolytic transfusion reactions can be confirmed in three ways:

• New unconjugated hyperbilirubinaemia causing jaundice
• Unexpected sudden drop in haematocrit
• Positive direct antiglobulin test

• It's very rare, largely due to leucodepletion
• 90% of cases are fatal
• Donor T cells attack recipient host tissues

Features:

• Maculopapular rash
• Abdominal pain
• Diarrhoea
• Deranged liver function
• Pancytopenia

Irradiating blood destroys or inactivates donor leucocytes, and generally avoids this problem.

• Previous exposure and sensitisation leads to antibody production on repeat exposure
• Similar to the issues seen when a rhesus-negative mother has a rhesus positive baby

• Patients that receive blood often demonstrate a period of immunosuppression afterwards
• This is probably due to the 'distraction' of the patient's white cells by the invading visitors

• Recheck the right blood is being transfused
• Rule out anaphylaxis as a priority
• Stop or slow the transfusion - restart slowly if symptoms settle
• Give paracetamol
• Consider chlorphenamine
• If severe reaction then stop and resuscitate with fluids, pressors, ventilatory support and adrenaline as required