Blood transfusions come with certain risks and complications. In this CCC we will be discussing different types of transfusion reactions.
Most of these reactions are immune mediated against foreign antigens.
🔢 Classification
We can classify transfusion reactions in a temporal manner as either acute or delayed:
- Acute transfusion reactions
These occur within 24 hours of transfusion.
- Acute haemolytic reaction
- Allergic transfusion reaction
- Febrile non-haemolytic transfusion
- Transfusion-related acute lung injury (TRALI)
- Transfusion-associated circulatory overload (TACO)
- Delayed transfusion reactions
Occur days-weeks after the transfusion.
- Delayed haemolytic reaction
- Transfusion-associated graft-versus-host disease
- Post-transfusion purpura
This is simply ABO incompatibility on erythrocytes. It is secondary to human error. Preformed IgM antibodies in the recipient attack antigens on the donor RBCs → complement activation and intravascular haemolysis. This can progress to DIC, shock and/or AKI.
😷 Presentation
- Chills
- Fever
- Headache
- Nausea and vomiting
- Pain - typically along the limb where the infusion was performed, or abdominal/chest/back pain.
- Haemoglobinuria
- Hypotension
- Renal failure
🔍 Investigations
- Check identity on blood product
- Direct Coombs test - used to assess for haemolytic anaemia. The indirect is used in prenatal testing for women. In a direct Coombs (antiglobulin) test, the patient blood is washed and incubated with Coombs reagent (antihuman IgG) which will attach to the antibodies coating the RBCs.
- Repeat ABO testing and crossmatching
🧰 Management
The initial step is of course to discontinue transfusion and initiate fluid resuscitation. We need to aim for a urine output of >100mL/hour to prevent oliguric renal failure. If the urine output is not adequate we may initiate forced diuresis (with mannitol).
- Supportive therapy such as ventilation, vasopressors, invasive haemodynamic monitoring may also be implemented.
Allergic transfusion reactions may present as a simple urticaria, however, it can also present with a full blown anaphylactic reaction.
It is a type 1 hypersensitivity reaction mediated by IgE, but in cases of patients who are IgA deficient there may be an anaphylactoid reaction due to anti-IgA antibodies attacking donor IgA.
😷 Presentation
- Pruritus
- Flushing
- Dyspnoea
- Urticaria
In cases of anaphylaxis, it could cause hypotension, angioedema, dyspnoea, wheezing and stridor.
🔍 Investigations
As anaphylaxis is a life-threatening emergency, investigations are not done prior to treatment. Instead they are taken after stabilisation to confirm anaphylactic reaction.
- Serum tryptase - may indicate anaphylaxis
- Serum IgA and anti-IgA antibodies - checking for anaphylactoid reaction.
🧰 Management
A - secure the airway.
B - provide oxygen if needed and salbutamol to aid dyspnoea.
C - provide a bolus of IV fluids.
D - keep the patient flat to increase cerebral perfusion.
E - assess for urticaria, flushing, etc.
- This is one of the few times when there is no time to look up the dose of medication. The Resuscitation Council has guidelines for anaphylaxis doses of IM adrenaline. IM adrenaline is by far the most important step in management and needs to be administered immediatel. It is usually given with an epipen auto-injector. It is best given in the anterolateral aspect of the middle 1/3rd of the thigh. It can be repeated every 5 minutes if need be.
- Glucagon may be given to patients taking ß-blockers as they may be resistant to adrenaline treatment. It produces a positive inotropic and chronotropic effect.
- Antihistamines such as diphenhydramine or cimetidine may also be given as an adjunct to adrenaline. If the patient has simply had a uriticarial reaction, then diphenhydramine may be given with temporary discontinuation of the transfusion.
- If the attack is prolonged, methylprednisolone may be given as well.
Recommended dosage is as follows:
Age | Dosage |
<6 months | 100-150mcg (0.1-0.15ml) |
6 months - 6 years | 150mcg (0.15ml) |
6 - 12 years | 300mcg (0.3ml) |
>12 years | 500mcg (0.5ml) |
→ If the patient had no complications and responded well to a single dose of IM adrenaline then they should be fast-tracked for discharge 2 hours after resolution.
→ If 2 doses of adrenaline were needed or the patient has had a previous biphasic reaction then they should remain admitted for at least 6 hours after symptom resolution.
→ If they require >2 doses of adrenaline, have severe asthma, have a possible ongoing reaction (e.g. due to slow release medication), present late at night, are in remote areas with poor access to healthcare, they need to be monitored for at least 12 hours after symptom resolution.
A multi factorial reaction due to antibodies directed against leukocytes present in the transfusion. Antigen-antibody complexes may result in complement binding and release pyrogens. It also may arise from the transfusion of proinflammatory cytokines and complement fragments within the transfusion.
It is usually benign but may mask the onset of acute haemolytic transfusion reaction.
It occurs in 1-2% of RBC transfusions and 10-30% of platelet transfusions.
😷 Presentation
- Fever
- Chills
🧰 Management
Simply paracetamol and monitoring.
It is a non-cardiogenic cause of pulmonary oedema due to granulocyte (neutrophil) activation within the pulmonary vessel → increased vascular permeability.
😷 Presentation
It generally starts 1-2 hours after blood transfusion.
- Hypoxia
- Dyspnoea
- Tachypnoea
- Pulmonary infiltrates on CXR
- Fever
- Tachycardia
- Hypotension
🔍 Investigations
- CXR - bilateral pulmonary infiltrates.
- FBC - eosinophilia and/or acute decrease in neutrophil count (but these are not necessary to prove/disprove diagnosis).
- ABG - shows hypoxaemia.
The criteria for TRALI is: acute onset of symptoms, absence of circulatory overload, bilateral pulmonary infiltrates on CXR and hypoxaemia.
🧰 Management
Supportive therapy - this includes supplemental oxygen or mechanical ventilation depending on the level of severity.
This is when there is a circulatory overload due to volume excess. It happens when there is a large volume of blood being given over a short period of time or if there is underlying cardiac or renal failure. It leads to pulmonary oedema and respiratory distress and is the leading cause of death with transfusion.
It is diagnosed clinically but supportive investigations such as BP measure (hypertension - this is the key difference between TACO and TRALI), CXR, fluid balance, ABG, BNP may support the diagnosis.
😷 Presentation
- Respiratory compromise (tachypnoea, dyspnoea, decreased SpO2)
- Pulmonary oedema (on examination and/or chest X-ray)
- CVS changes (tachycardia, hypertension, widened pulse pressure)
- Fluid overload (oedema, positive fluid balance, diuretic response)
- BNP or NT-pro BNP elevation
🧰 Management
Diuretics and oxygen supplementation are the first-line options as well as other treatments for cardiac failure.
Serious cases may need mechanical ventilation.
In graft-versus-host diseases, lymphocytes that are transfused from the donor begin to attack the host. The host is almost always immunocompromised (with leukaemia or lymphoma generally). It has a poor prognosis and rapidly progresses to death.
😷 Presentation
Symptoms begin 8-10 days after transfusion:
- Maculopapular rash
- Fever
- Diarrhoea
It ultimately ends up with bone marrow aplasia → death.
Unfortunately there are no successful treatment options. Immunosuppressive treatments can be tried non-specifically, but almost always fail.
This is a form of immune thrombocytopenia that occurs when platelet-containing transfusions have occurred. The recipient would have already been sensitised to a foreign platelet antigen that is present within the transfused platelets. This will lead to destruction of platelets (thrombocytopenia).
😷 Presentation
Patients present with disseminated purpura with bleeding from mucous membranes, GI and urinary tracts.
🔍 Investigations
We can confirm diagnosis with:
- Platelet antibody screen - most commonly HPA-1a is the antigen implicated.
🧰Management
- IV immunoglobulin