Aetiology
The aetiology of a transfusion reaction is specific to the type of reaction observed.
Acute transfusion reactions
Acute haemolytic
Allergic
Hypersensitivity reactions to allergens in the transfused component.
Febrile non-haemolytic transfusion
Considered to be immune-mediated, although the mechanism appears to be multifactorial.
Transfusion-related acute lung injury (TRALI)
Delayed transfusion reactions
Delayed haemolytic transfusion reactions
Generally non-preventable, and the result of an anamnestic antibody response to non-ABO red-cell antigens.
Transfusion-associated graft-versus-host disease
Primarily observed in immunodeficient patients in which transfused white cells react with recipient antigens, though it can occur in non-immunosuppressed patients if the blood components transfused are derived from a human leukocyte antigen (HLA) haplo-identical donor.[9]
Post-transfusion purpura
Occurs as a result of prior sensitisation to foreign platelet antigen, often during pregnancy.[4]
Pathophysiology
Acute transfusion reactions
Acute haemolytic
Typically result from ABO incompatibility. The presence of preformed recipient antibodies to donor antigens results in complement activation, leading to intravascular haemolysis and its associated severe acute inflammatory cascade, which may ultimately progress to disseminated intravascular coagulation, shock, and/or acute renal failure.[3][4][21]
Allergic transfusion
Typically manifests as urticaria caused by a hypersensitivity reaction to allergen proteins in donor plasma. In the most severe form, anaphylaxis (which is IgE-mediated) may occur.[4] In IgA-deficient patients, an anaphylactic reaction (technically anaphylactoid, as it is not IgE-mediated) can occur as a result of anti-IgA antibodies in the recipient interacting with donor IgA. [4][21][27]
Febrile non-haemolytic transfusion
May result in part from interaction between recipient antibodies directed against leukocytes present in the red-cell or platelet unit transfused. The formation of antigen-antibody complexes may result in complement binding and release of endogenous pyrogens. Febrile non-haemolytic transfusion reactions may also result from the transfusion of proinflammatory substances including cytokines, complement fragments, and lipid compounds that are contained in the transfused unit's plasma supernatant.[28]
Transfusion-related acute lung injury (TRALI)
Occurs secondary to priming of granulocytes in the pulmonary vasculature.[4][6] This phenomenon may be the result of antigranulocyte antibodies contained in donor plasma, priming by bioreactive substances such as lipids present in the transfused component, or a combination of the two mechanisms.[4][7][21][29]
Delayed transfusion reactions
Delayed haemolytic transfusion reactions
Result from non-ABO antigen-antibody incompatibilities. Typically, the recipient has had prior exposure to a foreign red-cell antigen following pregnancy, previous transfusion, or transplantation.[3] Exposure to the same antigen results in an anamnestic antibody response, leading to haemolysis, which is typically extravascular (in the reticuloendothelial system) and relatively benign.[3][21]
Transfusion-associated graft-versus-host disease
Occurs because viable transfused passenger lymphocytes in donor components mount an immunological attack against the recipient, who is almost always immunocompromised (by leukemia, lymphoma, or congenital immunodeficiency).[9] It may also occur in immunocompetent patients who are heterozygous for an HLA haplotype for which the donor is homozygous.[4][9][30]
Post-transfusion purpura
An immune thrombocytopenia that occurs after transfusion of a platelet-containing component (platelets, red cells, granulocytes). The recipient has been sensitised to a foreign platelet antigen (usually human platelet antigen 1a), most often during pregnancy, or alternatively from a past transfusion.[4] In post-transfusion purpura, both the antigen-positive donor platelets and antigen-negative recipient platelets are destroyed, resulting in thrombocytopenia.[4][21]
Classification
Types of transfusion reactions[2]
Acute immune-mediated
Acute haemolytic transfusion reactions
Usually the result of ABO red-cell incompatibility. Most often the result of clerical error resulting in mistransfusion.[3][4]
Symptoms such as chills and fever, headache, nausea and vomiting, and anxiety typically evolve during or immediately following a transfusion.
Pain along the infused extremity, or abdomen, chest, or back may accompany generalised symptoms.
Haemoglobinuria is often present. Severe acute haemolytic transfusion reaction may progress to hypotension, renal failure, and disseminated intravascular coagulation (DIC).[1]
The severity of the reaction is proportional to the amount of incompatible blood transfused.[3][4]
Allergic reactions
Hypersensitivity reactions to allergens in the transfused component.
Symptoms include pruritus, flushing, and dyspnoea.
Symptoms often occur within minutes of the initiation of transfusion.
Urticaria typically evolves and, less commonly, angio-oedema develops.
Anaphylaxis - a serious, potentially life-threatening, systemic allergic reaction - may follow.[5] Anaphylaxis is generally rapid in onset, with variable signs and symptoms, and typically affects two or more body systems (e.g., cutaneous, respiratory, cardiovascular).[5] However, atypical presentations may only appear to affect a single system (e.g., isolated hypotension).[5] There may be features of respiratory compromise (e.g., dyspnoea, wheezing, stridor, hypoxaemia, reduced peak expiratory flow) and/or cardiovascular compromise or associated end-organ dysfunction (e.g., hypotension, hypotonia/collapse, syncope, incontinence).[5] Gastrointestinal symptoms may also be present (e.g., cramping abdominal pain, vomiting, diarrhoea).[5] It should be noted that typical cutaneous features of anaphylaxis (e.g., urticaria, flushing, pruritus, angio-oedema) are not always present.[5]
Febrile non-haemolytic transfusion reactions
Considered to be immune-mediated, although the mechanism appears to be multifactorial.
Present with fever, defined as a rise in temperature of at least 1°C (1.8°F ) above 37°C (98.6°F) for which no other cause is identifiable.
Most episodes are benign, but initially may be indistinguishable from the onset of an acute haemolytic transfusion reaction.
Transfusion-related acute lung injury (TRALI)
Occurs as a result of granulocyte activation in the pulmonary vasculature, resulting in increased vascular permeability.[4][6]
Characterised by the sudden onset of dyspnoea and tachypnoea, often accompanied by fever and tachycardia.
Hypotension may also be observed.
Onset is typically within 1 to 2 hours following the transfusion of any blood product, but onset has been observed during transfusion to 6 hours following transfusion, and by definition occurs within 6 hours of the transfusion.[4][6][7][8]
Delayed immune-mediated
Delayed haemolytic transfusion reactions
Generally non-preventable, and the result of an anamnestic antibody response to non-ABO red-cell antigens.
Present with fever or anaemia occurring days to weeks following transfusion.
Jaundice may develop.
Haemoglobinuria may be observed as red urine due to extravascular haemolysis.
Acute renal failure and DIC rarely occur.
Delayed haemolysis may occur in the absence of symptoms. The diagnosis may be made when a new positive direct antiglobulin test and/or positive antibody screen is identified during the preparation of a subsequent transfusion.[3]
Transfusion-associated graft-versus-host disease[9]
Rare, and primarily observed in immunodeficient patients in whom transfused white cells react with recipient antigens.
Symptoms, which include maculopapular rash, fever, and diarrhoea, usually begin 8 to 10 days following transfusion.
Tends to lead to marrow aplasia, with rapid progress towards death.
Post-transfusion purpura
Occurs as a result of prior sensitisation to foreign platelet antigen, usually during pregnancy.
Patients present with disseminated purpura.
Bleeding from mucous membranes, GI tract, and urinary tract may occur due to thrombocytopenia.
Non-immune-mediated
Non-immune haemolysis.
Transfusion-associated sepsis.
Transfusion-associated circulatory overload.
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