Transfusion Reactions

Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody–mediated. Symptoms can range from mild itching, chills, and urticaria (hives) to high fever, severe shortness of breath, jaundice, hypotension, or hemoglobinuria. Severe reactions can lead to death.

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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
Hemolytic reaction symptoms

Signs and symptoms of acute hemolytic transfusion reactions

Image: “Main symptoms of acute hemolytic reaction” by Mikael Häggström. License: Public Domain, edited by Lecturio.

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
Transfusion-related acute lung injury chest X-ray

Chest X-ray of TRALI showing bilateral diffuse infiltrates (left); chest X-ray of the same subject after treatment (right)

Image: “Two chest X-rays” by Altaf Gauhar Haji et al. License: CC BY 2.0, edited by Lecturio.

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

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