ImmunologyTier 1Medical Sciences concept

Transfusion reactions - types, mechanisms, and relative frequency

Core concept

Transfusion reactions are classified by mechanism and timing -- matching presentation to type (and to the causative immunoglobulin/process) is the exam task
Acute haemolytic transfusion reaction (AHTR): ABO incompatibility, IgM-mediated, complement-activating, intravascular haemolysis -- the most dangerous, almost always due to clerical/identification error, not a laboratory typing failure
Febrile non-haemolytic transfusion reaction (FNHTR): the most common reaction overall -- cytokines from donor leukocytes (and recipient antibodies to donor leukocyte antigens) accumulated during storage

Reaction	Mechanism	Timing	Key feature
AHTR	IgM anti-A/B, complement-mediated intravascular haemolysis	Minutes-hours	Fever, hypotension, flank pain, haemoglobinuria, DIC -- stop transfusion immediately
FNHTR	Cytokines from donor WBCs/recipient anti-leukocyte antibodies	During/soon after	Fever, chills, no haemolysis -- diagnosis of exclusion
Delayed haemolytic reaction	Anamnestic IgG response to minor RBC antigens (Rh, Kidd, Duffy)	Days-weeks	Extravascular haemolysis, falling Hb, positive DAT
TRALI	Donor anti-leukocyte antibodies activate recipient neutrophils in the lung	Within 6h	Non-cardiogenic pulmonary oedema
TACO	Volume overload	During/soon after	Hypertension, signs of fluid overload (distinguishes from TRALI)
Anaphylactic	IgA deficiency with anti-IgA antibodies (or other allergen)	Seconds-minutes	Can occur with minimal volume infused

The commonest cause of a fatal acute haemolytic reaction is a clerical error (wrong patient/unit identification) -- reinforces why bedside identity checks matter more than laboratory crossmatch accuracy
Leukoreduction (removing donor white cells from the unit before storage) reduces FNHTR incidence -- reduced cytokine accumulation during storage, and reduced HLA alloimmunisation
Trap: distinguishing TRALI from TACO -- both present with acute respiratory distress during/after transfusion, but TACO shows hypertension and fluid-overload signs (raised BNP, response to diuretics), TRALI does not

AHTR's IgM mechanism - see antibody affinity vs avidity; IgM's pentameric structure and low individual affinity but high avidity make it an efficient complement activator even at low antigen density
Anaphylactic transfusion reactions in IgA-deficient patients connect to coeliac disease's IgA-deficiency association (false-negative IgA-based serology) -- same underlying immunodeficiency, different clinical context
Delayed haemolytic reaction's IgG/anamnestic mechanism parallels HLA sensitisation from prior exposure (transfusion, pregnancy, transplant)

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