History and exam

Key diagnostic factors

common

presence of risk factors

Strong risk factors include ABO incompatibility (unusual, and typically results from clerical error), pregnancy or transfusion (associated with sensitisation to antigens predisposing to future reactions), transplantation and immunocompromised status (associated with graft-versus-host disease), IgA deficiency (associated with anaphylactoid reaction), and prior history of transfusion reaction.

chills

May be associated with either acute haemolytic reaction or febrile non-haemolytic reaction.[1][3]

flushing

Typical with an allergic transfusion reaction.

Often occurs within minutes of the initiation of transfusion.

dyspnoea

Typical with an allergic transfusion reaction.

Often occurs within minutes of the initiation of transfusion.

Also associated with transfusion-related acute lung injury (TRALI), in which case onset is typically within 1 to 2 hours following transfusion and by definition occurs within 6 hours of transfusion.[6][7][8]

fever

May indicate acute haemolytic reaction, febrile non-haemolytic reaction, transfusion-related acute lung injury (TRALI), delayed haemolytic transfusion reaction, or graft-versus-host disease.[3]

Fever is defined as a rise in temperature of at least 1.8°F (1°C) above 98.6°F (37°C) for which no other cause is identifiable.

When remote from transfusion, diagnosis of delayed haemolytic transfusion reaction should be considered. Delayed haemolytic transfusion reaction may present with fever occurring days to weeks following transfusion.

Also commonly occurs with onset of TRALI.

Transfusion-associated graft-versus-host disease may present with fever, usually 8 to 10 days following transfusion, and typically occurs in immunocompromised patients.

uncommon

chest, abdominal, flank, and back pain

Characteristic of acute haemolytic reaction.[3]

hypotension

Associated with acute haemolytic reaction.[3]

Also associated with anaphylactic reaction.

bleeding from mucous membranes, GI tract, or urinary tract

May occur with severe acute haemolytic transfusion reaction that can lead to renal failure and disseminated intravascular coagulation (DIC). Patients may develop uraemia or DIC with concomitant platelet dysfunction.

The severity of the reaction is proportional to the amount of incompatible blood transfused.[3][4]​​

Other diagnostic factors

common

headache

May be associated with either acute haemolytic reaction or febrile non-haemolytic reaction.

nausea and vomiting

May be associated with either acute haemolytic reaction or febrile non-haemolytic reaction.

May occur during an anaphylactic reaction.[5]

anxiety

Signs and symptoms of an acute reaction typically evolve during or immediately following transfusion.

May be associated with either acute haemolytic reaction or febrile non-haemolytic reaction.

pain along the infused extremity

A specific symptom for acute haemolytic transfusion reaction.

pruritus

Typical with an allergic transfusion reaction.

Often occurs within minutes of the initiation of transfusion.

urticaria

Indicates allergic reaction to transfusion.

More common than angio-oedema.

angio-oedema

Indicates allergic reaction to transfusion.

Angio-oedema is less common than urticaria.

jaundice

Some patients with delayed haemolytic transfusion reaction develop jaundice.[3]

rales

May be appreciated in transfusion-related acute lung injury (TRALI).

uncommon

red urine

Associated with acute haemolytic reaction and haemoglobinuria.[3]

May be the first sign of intravascular haemolysis, particularly in non-communicative, sedated, or ventilated patients.

stridor or bronchospasm

Associated with anaphylactic reaction to transfusion.

May follow other signs of allergic reaction.

pallor

Delayed haemolytic transfusion reaction may present with pallor due to anaemia occurring days to weeks following transfusion.[3]

maculopapular rash

Associated with transfusion-associated graft-versus-host disease.[9]

Symptoms usually begin 8 to 10 days following transfusion.

May progress to toxic epidermal necrolysis.

diarrhoea

Associated with transfusion-associated graft-versus-host disease.[9]

Symptoms usually begin 8 to 10 days following transfusion.

May occur more acutely during an anaphylactic reaction.[5]

disseminated purpura

Associated with post-transfusion purpura.

Patient will often have associated bleeding from mucous membranes, GI tract, and urinary tract, and may develop associated thrombocytopenia.

exfoliative dermatitis with mucocutaneous involvement

Toxic epidermal necrolysis may occur with transfusion-associated graft-versus-host disease.

Risk factors

strong

prior pregnancy

Associated with delayed haemolytic transfusion reactions.[3][4]​​ They are the result of non-ABO antigen-antibody incompatibilities in which the recipient has had prior exposure to a foreign red-cell antigen.

Pregnancy is also associated with post-transfusion purpura.[4]

previous transfusion

Associated with delayed haemolytic transfusion reactions.[3]​ They are the result of non-ABO antigen-antibody incompatibilities in which the recipient has had prior exposure to a foreign red-cell antigen.

history of transplantation

Associated with delayed haemolytic transfusion reactions.[3]​ They are the result of non-ABO antigen-antibody incompatibilities in which the recipient has had prior exposure to a foreign red-cell antigen.

Transplant recipients are also at risk for transfusion-associated graft-versus-host disease.[9]

IgA deficiency

Associated with anaphylactoid reaction due to recipient anti-IgA response to the blood product.[27] Anaphylactoid reaction is distinguished from anaphylactic reaction in that anaphylactic reactions are due to IgE.

immunocompromise

Patients with immunocompromise such as lymphoma, leukemia, and congenital immune deficiencies are at risk for transfusion-associated graft-versus-host disease.[9]

history of transfusion reaction

A history of prior transfusion reaction should trigger additional testing for compatibility of blood products.

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