Transfusion reactions are adverse events associated with blood product administration. They range from mild and self-limited to life-threatening emergencies. Prompt recognition, immediate management, and thorough laboratory investigation are essential for patient safety and for preventing recurrence.

Acute Hemolytic Transfusion Reaction

Acute hemolytic transfusion reaction (AHTR) is the most dangerous transfusion reaction, typically caused by ABO incompatibility (patient anti-A/anti-B reacting with donor RBC antigens). Onset is during or within minutes of transfusion. Symptoms include fever, chills, back/flank pain, chest tightness, hypotension, dark urine (hemoglobinuria), and diffuse bleeding (DIC). Laboratory findings: hemoglobinemia (pink plasma), hemoglobinuria, elevated LDH, low haptoglobin, positive direct antiglobulin test (DAT), and positive repeat crossmatch. Management is immediate cessation of transfusion, IV fluid resuscitation, vasopressor support, and treatment of DIC and renal failure. Prevention relies on rigorous patient identification prior to transfusion. AHTR has a mortality of 5–10%.

Delayed Hemolytic Transfusion Reaction

Delayed hemolytic transfusion reaction (DHTR) occurs 2–10 days post-transfusion in patients with prior alloimmunization whose antibody titer had fallen below detectable levels (anamnestic response). Common antibodies include anti-Kidd (Jkᵃ, Jkᵇ), anti-Duffy (Fyᵃ), anti-E, and anti-K. Symptoms are milder than AHTR: falling hemoglobin, jaundice, low-grade fever, and a positive DAT (mixed field). The antibody screen becomes positive. Management is supportive; most patients recover without specific treatment. Prevention requires careful record-keeping of known antibodies and provision of antigen-negative blood.

Febrile Non-Hemolytic Transfusion Reaction

Febrile non-hemolytic transfusion reaction (FNHTR) is the most common reaction, occurring in 1–3% of transfusions. Fever (≥ 38°C or ≥ 1°C rise) with chills and rigors during or within 4 hours of transfusion. It is caused by cytokines accumulated in stored blood products (especially platelets) or recipient antibodies reacting with donor leukocytes. Diagnosis is one of exclusion: infection, hemolysis, and bacterial contamination must be ruled out. Management: stop transfusion, exclude hemolysis (visual inspection, DAT, haptoglobin), administer antipyretics. Prestorage leukoreduction has significantly reduced FNHTR incidence.

Allergic and Anaphylactic Reactions

Mild allergic reactions (urticaria, pruritus, flushing) occur in 1–3% of transfusions, caused by recipient antibodies to donor plasma proteins. They are treated by temporarily stopping the transfusion and administering antihistamines; the transfusion can be resumed if symptoms resolve. Severe anaphylactic reactions are rare (< 1:20,000) but life-threatening, presenting with hypotension, bronchospasm, angioedema, and shock. Patients with IgA deficiency (who have anti-IgA antibodies) are at highest risk and require washed blood products or IgA-deficient donor units. Plasma products are contraindicated in these patients.

Transfusion-Related Acute Lung Injury (TRALI)

TRALI is the leading cause of transfusion-related mortality. It presents as acute respiratory distress within 6 hours of transfusion: severe hypoxemia (PaO₂/FiO₂ < 300), bilateral pulmonary infiltrates on chest X-ray, and no evidence of circulatory overload (normal CVP, normal BNP). TRALI is caused by donor antibodies (anti-HLA, anti-HNA) that activate recipient neutrophils in the pulmonary microvasculature, causing capillary leak. Management is supportive with supplemental oxygen and mechanical ventilation as needed. Prevention: use of male-only or never-transfused female plasma donors (reducing anti-HLA/HNA antibodies). Mortality is 5–15%.

Transfusion-Associated Circulatory Overload (TACO)

TACO presents with respiratory distress, hypertension, tachycardia, and elevated BNP during or within 6–12 hours of transfusion, due to circulatory volume overload. Risk factors include age > 70, pre-existing heart failure, renal impairment, and rapid transfusion rate. Management: stop transfusion, diuretics (furosemide), supplemental oxygen, and supportive care. Prevention: transfusion at slower rates, use of smaller volumes, and pre-transfusion diuretics in high-risk patients.

Bacterial Contamination

Bacterial contamination, especially of platelet concentrates (stored at room temperature), is the most common infectious complication of transfusion. Symptoms (fever, chills, hypotension, shock) begin during or shortly after transfusion. Gram-negative organisms (Serratia, Klebsiella, Pseudomonas, E. coli) and Gram-positive organisms (Staphylococcus, Bacillus) are most common. Management: immediate cessation of transfusion, blood cultures from the patient and the product, broad-spectrum antibiotics, and vasopressor support. Bacterial detection by culture (BacT/ALERT) with negative-to-date release and pathogen reduction technology have reduced the risk.

Transfusion-Associated Graft-Versus-Host Disease (TA-GVHD)

TA-GVHD is a rare but almost uniformly fatal complication in which donor T-lymphocytes engraft and attack recipient tissues. It presents 1–6 weeks post-transfusion with fever, rash (erythematous maculopapular), diarrhea, hepatitis, and pancytopenia. Diagnosis is confirmed by skin biopsy and detection of donor chimerism (HLA typing). No effective treatment exists; prevention by gamma irradiation of cellular products for at-risk patients is essential.