Learning Objective
LO: Distinguish between the major immunologic blood transfusion reactions (allergic/anaphylactic, acute hemolytic, febrile nonhemolytic, TRALI, and delayed hemolytic), including their immunologic mechanism, timing, and key clinical features for rapid Step 1 recognition.
Allergic / Anaphylactic Reaction
Type: Type I hypersensitivity
Mechanism: Host IgE antibodies react to plasma proteins in donor blood.
- IgA-deficient patients may form anti-IgA IgE, → severe anaphylaxis
Timing: Minutes to 2–3 hours
Clinical Features:
- Mild: urticaria, pruritus
- Severe: wheezing, hypotension, respiratory arrest, shock
Key Immunologic Players:
- Donor: plasma proteins (including IgA)
- Host: IgE on mast cells
Activity
Acute Hemolytic Transfusion Reaction
Type: Type II hypersensitivity
Mechanism: Preformed anti-A or anti-B IgM/IgG → complement-mediated intravascular hemolysis
Timing: During transfusion or ≤ 24 hours
Clinical Features:
- Fever, hypotension
- Tachycardia, tachypnea
- Flank pain
- Hemoglobinuria (intravascular hemolysis)
- Jaundice (extravascular component possible)
Key Immunologic Players:
- Donor: RBCs with A/B antigens
- Host: anti-A or anti-B antibodies
Activity
Febrile Nonhemolytic Transfusion Reaction
Type: Non-IgE; Cytokine-mediated
Mechanism: Cytokines released from donor WBCs accumulate during storage; host anti-HLA or anti-WBC IgG may contribute
Timing: 1–6 hours after transfusion
Clinical Features:
- Fever, chills, headache, flushing
- Common in pediatrics
Prevention: Leukoreduction of donor blood
Key Players:
- Donor: WBC-derived cytokines
- Host: anti-HLA / antileukocyte IgG
Activity
TRALI (Transfusion-Related Acute Lung Injury)
Type: Immune-mediated lung injury
Mechanism (Two-hit):
- Recipient neutrophils are primed in the pulmonary vasculature.
- Donor anti-leukocyte antibodies activate neutrophils → inflammatory damage → ↑ capillary permeability → non-cardiogenic pulmonary edema
Timing: Minutes to 6 hours
Clinical Features:
- Acute respiratory distress
- Bilateral pulmonary infiltrates
- Non-cardiogenic pulmonary edema
Key Players:
- Donor: anti-leukocyte antibodies
- Host: neutrophils
Delayed Hemolytic Transfusion Reaction
Type: Anamnestic (secondary immune) response
Mechanism: Host previously sensitized to minor RBC antigens (e.g., Rh[D], Kidd, Duffy) → slow production of IgG → extravascular hemolysis
Timing:
- Usually 1–2 weeks, can be >24 hours
Clinical Features:
- Often mild or asymptomatic
- Low-grade fever
- Hyperbilirubinemia
- Gradual fall in hemoglobin
Key Players:
- Donor: RBC minor antigens
- Host: IgG from memory B cells








