Hematology: Transfusion Reactions

Acute Transfusion Reactions

Electrolyte Abnormalities

  • HypocalcemiaCitrate Chelation After Massive Transfusion
  • Hyperkalemia – High Potassium Concentration in Stored PRBC (Due to Lysis During Storage)
  • Metabolic AlkalosisCitrate is Metabolized to Bicarbonate

Mild Allergic (Urticarial) Reaction

  • Cause: Host IgE Reacts to Soluble Substances in Donor Plasma
    • Initiates Release of Histamine by Mast Cells & Basophils
  • Timing: 2-3 Hours
  • Presentation: Urticaria (Hives) & Pruritis
  • Clinical Diagnosis
  • Treatment: Diphenhydramine (Benadryl)
    • Should Stop Transfusion – But Can Resume if Urticaria Improves

Anaphylaxis

  • Cause: Sudden Massive Release of Histamine by Mast Cells & Basophils
    • Allergy to Transfusion Contents (IgE or IgG-Mediated Immune Reaction)
    • Host Antibody to Donor IgA (Seen in IgA Deficiency Patients)
  • Timing: Seconds-Minutes
  • Presentation:
    • Bronchospasm/Wheezing
    • Shock
    • Angioedema
  • Clinical Diagnosis
  • Treatment: Epinephrine & Stop Transfusion

Febrile Nonhemolytic Transfusion Reaction (FNHTR)

  • The Most Common Transfusion Reaction
  • Cause: Host Antibody to Donor Cytokines
    • Prevent by Leukoreduction
  • Timing: Minutes-Hours
  • More Common After PRBC and Platelet Transfusions than Plasma
    • Highest Risk with Whole Blood-Derived Platelets (Compared to Apheresis)
  • Presentation:
    • Fever
    • Chills/Rigors
  • Clinical Diagnosis
  • Treatment: Stop Transfusion

Acute Hemolytic Transfusion Reaction

  • Cause: Hemolysis Due to ABO Incompatibility (Host Antibody to Donor RBC)
  • Timing: < 24 Hours
  • Presentation:
    • “Classic Triad”: Rarely Seen
      • Fever
      • Flank Pain
      • Hemoglobinuria (Red Urine)
    • Acute Tubular Necrosis (ATN)
    • Disseminated Intravascular Coagulation (DIC)
  • Treatment: Stop Transfusion, Aggressive Fluid Resuscitation (Normal Saline) & Hemodynamic Support
    • Medical Emergency
    • Goal Urine Output > 1 cc/kg/Hour
    • Consider Diuresis if Hemodynamically Stable with Signs of Overload

Transfusion-Related Acute Lung Injury (TRALI)

  • Definition: New Acute Lung Injury/ARDS Occurring within 6 Hours of Transfusion
  • Cause:
    • Host Neutrophils are Sequestered in the Lung Microvasculature
    • Host Neutrophils are Activated by Donor Factors Causing Release of Inflammatory Mediators & Pulmonary Edema
      • Can Be Caused by Donor Antibodies Against Host Leukocytes
  • Timing: < 6 Hours
  • Presentation:
    • Pulmonary Edema
    • Hypoxemia
    • Fever
    • Pink Frothy Airway Secretions
  • Most Common Cause of Death after Transfusion
  • Treatment: Stop Transfusion & Hemodynamic Support
    • Most Will Require Ventilatory Support (70-80%)
    • Utilize Lung Protective Strategy for Ventilation – Similar to ARDS

Transfusion-Associated Circulatory Overload (TACO)

  • Definition: At Least 3 of the Following within 12 Hours of Transfusion
    • Respiratory Distress
    • Pulmonary Edema
    • Elevated BNP
    • Other Unexplained Cardiovascular Changes
  • Cause: Pulmonary Edema Due to Circulatory Volume Overload
    • Most Common After a Large Volume Transfusion with Underlying Heart Failure
  • Timing: < 12 Hours
  • Presentation:
    • Respiratory Distress
    • Headache
  • Treatment: Stop Transfusion, Diuretics & Hemodynamic Support
    • May Require Ventilatory Support

Infection/Sepsis

  • Due to Transfusion of Infected Blood Products
  • Timing: 9-24 Hours
  • Microbiology:
    • Bacterial Infection More Common Than Viral Infection
    • Most Common Organism: Gram Negative Rods (Escherichia coli, etc.)
    • HIV & Hepatitis Carry a Risk in All Transfusions Except Albumin & Serum Ig
      • Heat Treated Prior to Packaging
  • Donated Blood is Screened For: HIV, HBV, HCV, HTLV, Syphilis & West Nile Virus
  • Most Common Source: Platelet Transfusion (Stored at Room Temperature)
  • Presentation:
    • Fever
    • Chills
    • Hemodynamic Instability
  • Treatment: Antibiotics & Hemodynamic Support

Post-Transfusion Purpura (PTP)

  • Cause: HPA-1a Platelet Antibody
    • Must Have Been Previously Sensitized – Pregnancy or Transfusion
  • Usually Presents 5-12 Days After Transfusion
  • Presentation:
    • Thrombocytopenia (Often Severe < 15,000-20,000)
    • Profound Bleeding
    • Purpura
  • Diagnosis: HPA-1a Antibody Testing
  • Treatment: IVIG
    • Platelet Transfusions Can Exacerbate the Disease Process

Delayed Transfusion Reactions

Delayed Hemolytic Transfusion Reaction

  • Cause: Hemolysis from Anamnestic Antibody Response
    • Previously Sensitized to RBC Antigens (Most Common are Kidd or Rh System)
  • Can Occur as an Unexpected Ab if Formed from a Previous Transfusion
    • Prevent by Retyping and Screening
  • Timing: Days-Weeks
  • Presentation:
    • Fever
    • Jaundice
    • Anemia
    • *Generally More Mild than Acute Hemolytic Transfusion Reactions
  • Treatment: Observation

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

  • Cause: Donor Lymphocytes Attack Host Tissue
    • Attack Bone Marrow, Skin & GI Tract
    • Higher Risk with Immunodeficiency
  • Prevented by Irradiation
  • Timing: 2-30 Days
  • Presentation:
    • Rash
    • Pancytopenia
    • Fever
    • Diarrhea
    • Hepatomegaly & Transaminase Elevation
  • High Mortality: 80-90%
  • Treatment: Hematopoietic Stem Cell Transplant if Available – Rarely Available or Sufficient Time to Prepare/Obtain
    • No Other Effective Treatments