Transfusion Reactions

Hemolytic Reactions

Acute hemolytic transfusion reaction

• Etiology:
  • Type II hypersensitivity reaction→ targets the transfused RBCs
  • ABO blood group incompatibility causes intravascular hemolysis.
  • Host’s own antibodies (immunoglobulin G (IgG)) detect and bind to antigens on donor RBCs, causing extravascular hemolysis.  
• Signs and symptoms:
  • Start during the transfusion or within 1 hour after
  • Tachycardia
  • Tachypnea
  • Hypotension
  • Flank pain
  • Hemoglobinuria due to intravascular hemolysis
  • Jaundice due to the extravascular hemolysis (yellowing of the sclera and skin)
  • Fever and chills
• Management: 
  • Immediate cessation of transfusion 
  • Repeat typing and crossmatching to identify cause and record to prevent future reactions.
  • Supportive care:
    • Infusion of IV fluids to aid diuresis
    • Hypotension managed with IV fluids and vasopressors 
    • In case of disseminated intravascular coagulation (DIC): Perform coagulation studies and administer of fresh frozen plasma (FFP) and platelets. 
• Complications:
  • Hemoglobinuria can lead to renal tubular necrosis and renal failure.
  • DIC: severe hemolysis can lead to an accumulation of cytokines in the blood → hypercoagulation → microthrombi and hemorrhage → impaired perfusion of organs and tissue necrosis → multi-system organ failure

Delayed hemolytic transfusion reaction

• Etiology:
  • Occurs in patients who have been sensitized to specific RBC antigens (previous transfusions, pregnancy, or transplantations) 
  • Re-exposure stimulates rapid antibody production and leads to extravascular hemolysis.
• Signs and symptoms: 
  • Starts days or weeks after the transfusion
  • Fever and chills
  • Jaundice 
  • Anemia
  • Hemoglobinuria
• Management:
  • No treatment required
  • Antibody testing should be performed to prevent future reactions.

Nonhemolytic Reaction

Febrile nonhemolytic transfusion reaction (FNHTR)

• Etiology:
  • Type II hypersensitivity reaction in which host antibodies target donor leukocytes
  • Accumulation of cytokines (IL-1, IL-6, IL-8, and tumor necrosis factor (TNF)) in the donor blood during storage produces an immune reaction in the recipient.
• Signs and symptoms:
  • Start within 1–6 hours after transfusion
  • Fever and chills
  • Headaches 
  • Flushing
  • General malaise
• Management:
  • Cessation of transfusion 
  • CBC to rule out acute hemolytic reaction (anemia, hyperbilirubinemia, thrombocytopenia)
  • Acetaminophen to aid with fever
  • Prevention by leukoreduction of blood products

Allergic Reactions

• Etiology:
  • Type I hypersensitivity reaction against plasma proteins in donor blood
  • In the case of IgA deficiency: the anti-IgA IgG antibodies of the recipient detect the IgA on the surface of RBCs in the donor blood, triggering a mass release of cytokines → anaphylaxis
• Signs and symptoms: 
  • Start during the transfusion or within 2 hours after
  • Minor allergic reactions: urticaria or pruritus
  • Life-threatening reaction (anaphylaxis):
    • Hypotension
    • Bronchospasm, wheezing, or stridor
    • Nausea and/or vomiting
    • Shock
    • Cardiac and/or respiratory arrest
• Management:
  • Minor allergic reactions: antihistamines (e.g., diphenhydramine)
  • Anaphylaxis: 
    • Epinephrine
    • Hemodynamic stabilization
    • Airway management

Other Types of Transfusion Reactions

Transfusion-related acute lung injury (TRALI)

• Etiology:

• Antibodies in the donor blood products target the neutrophils and pulmonary endothelial cells of the recipient.
• Causes non-cardiogenic pulmonary edema
• Can lead to acute hypoxemia
• Activated neutrophils in the lungs may also secrete proteolytic enzymes, leading to more tissue damage.
• Signs and symptoms: 
  • Start during the transfusion or within 6 hours after
  • Respiratory distress or dyspnea
  • Hypotonia
  • Fever
  • Hypotension (hypovolemia due to the accumulation of fluid in the lungs)
  • X-ray shows bilateral infiltrates suggesting pulmonary edema.
• Management:
  • Cessation of transfusion
  • Supportive care
    • Assisted ventilation or oxygen administration
    • Monitoring and regulation of hemodynamic parameters
    • IV steroids to aid with inflammation

Graft-versus-host disease (GvHD)

• Etiology:
  • Delayed transfusion reaction 
  • Donor’s T lymphocytes target the recipient’s tissues and organs and produce →  systemic inflammatory reaction.
  • Most commonly affected organs: skin, intestines, and liver
  • Immunocompromised or immunocompetent patients are most likely to develop this condition.
  • Can present acutely (< 100 days after transfusion/transplant) or chronically (> 100 days after transfusion/transplant)
• Signs and symptoms:
  • Acute reaction
    • Starts < 100 days after transfusion/transplant
    • Pruritic, painful maculopapular rash
    • Nausea and/or vomiting
    • Diarrhea and cramping abdominal pain
    • Jaundice
  • Chronic reaction
    • Starts > 100 days after transfusion/transplant
    • All symptoms seen in the acute reaction may occur. 
    • Scleroderma-like skin changes (lichenoid skin changes)
    • Xerostomia (dry mouth) and xerophthalmia (dry eyes)
    • Bloody diarrhea (chronic enteritis similar to inflammatory bowel disease (IBD))
    • Weight loss
    • Muscle pain and weakness
    • Bronchiolitis obliterans (chronic/persistent cough, wheezing, and dyspnea)
• Diagnosis:
  • CBC shows anemia, thrombocytopenia, and/or leukopenia (acute reaction).
  • Spirometry may show obstructive lung disease (chronic reaction).
  • Biopsy of the transplanted tissue to confirm diagnosis 
• Management:
  • 1st-line: corticosteroids 
    • Topical in the case of  < 50% skin involvement
    • Systemic in the case of > 50% skin involvement, gastrointestinal (GI) involvement, liver involvement
  • 2nd-line: increased corticosteroid dose + immunosuppressant (e.g., cyclosporine)

Transfusion-associated circulatory overlaad (TACO)

• Etiology:
  • Large transfusion volume
  • Fast infusion rate
  • Underlying renal or cardiovascular disease
  • Low body weight
  • Infant or elderly patients
• Signs and symptoms: 
  • Start during the transfusion or within 6 hours after
  • Signs of hypervolemia 
    • S3 gallop
    • Shortness of breath
    • Jugular venous distention
    • Sudden hypertension
    • Tachycardia
    • Widened pulse pressure
    • Cough and/or dyspnea
  • X-ray shows bilateral infiltrates suggesting pulmonary edema.
• Management:
  • Diuretics (only method to counteract elevated blood volume)
  • Oxygen supplementation or assisted ventilation if necessary