Transfusion Complications

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Basics

Epidemiology

  • A 2007 study found that there are ∼14.6 million blood transfusions per year
  • In 2015 there were 37 deaths in the U.S. fully attributable to transfusion complications
  • Some type of transfusion reaction occurs in 2% of units transfused within 24 hr
  • Noninfectious complications:
    • Febrile nonhemolytic reaction: Most common: Occurs in 0.1–1% of transfusions; more common in kids; platelets 1 in 900
    • Allergic reaction (nonanaphylactic): Common; 1 in 100–1 in 33 transfusions
    • Anaphylaxis: 1 in 20,000–1 in 50,000
    • Acute hemolytic reaction: 1 in 38,000–1 in 70,000; resulting in 5 deaths per 10 million transfusions
    • Delayed hemolytic reaction: 1 in 4,000–1 in 11,000
    • Transfusion-associated circulatory overload (TACO): 1 in 100, but as high as 10% in susceptible populations
    • Alloimmunization: 1 in 10–1 in 100
    • Graft vs. host disease: 1 in 400,000; rare but has >90% mortality
    • Transfusion-related lung injury (TRALI): 1 in 5,000–1 in 190,000; represents 13% of reported transfusion-related deaths
    • Iron overload: Unknown incidence, depends on volume of blood, often occurs after >100 RBC units
    • Hypocalcemia: Unknown incidence
    • Hyperkalemia: Unknown incidence
  • Infectious complications:
    • Bacterial contamination: RBCs 1 in 65,000–1 in 500,000; platelets 1 in 1,000–1 in 10,000:
      • Most common bacterial agents: Yersinia enterocolitica, Pseudomonas spp., Serratia spp., S. aureus
      • Leading cause of mortality among infectious complications; 17–22% of all cases
    • Hepatitis C: 1 in 1.6 million
    • Hepatitis B: 1 in 100,000–1 in 400,000
    • HTLV I and II: 1 in 500,000– 1 in 3 million
    • HIV: 1 in 1.4 million–1 in 4.7 million
    • HAV: 1 in 1,000,000
    • B19 parvovirus: 1 in 40,000; posttransfusion anemia rare with scattered case reports
    • Parasites: Babesia and malaria: <1 in 1 million
    • Parasites: Trypanosoma cruzi: 1 in 42,000
    • Case reports of Epstein–Barr virus, Lyme disease, brucellosis, human herpesvirus, Creutzfeldt–Jakob disease

Acute Intravascular Hemolytic Transfusion Reaction
  • Mortality and morbidity correlate with amount of incompatible blood transfused (symptoms can occur with exposure to as little as 5–20 mL)
  • Usually due to lab error
  • Occurs immediately from:
    • ABO incompatibility (most common)
    • Also from other antigen incompatibility, i.e., Kell, JK
  • Intravascular hemolysis causing activation of coagulation system, leading to inflammation, shock, and DIC
  • Mediators (cytokines) released during inflammatory response
  • Clinically may see chills, fever, hypotension, hemoglobinuria, back pain, and DIC
  • Renal failure:
    • Cytokines cause local release of endothelin in kidney, causing vasoconstriction
    • Leads to parenchymal ischemia and acute renal failure
  • Respiratory failure owing to pulmonary edema/adult ARDS:
    • Free hemoglobin (Hb) causes vasoconstriction in pulmonary vasculature

Other Transfusion-Related Complications
  • Hemolysis because of Rh incompatibility:
    • Mild, self-limiting
    • 1:200 U transfused
  • Febrile nonhemolytic transfusion reaction:
    • Most common transfusion reaction, diagnosis of exclusion
    • Temperature increases at least 1°C with chills within 6 hr
    • Caused by cytokines generated in the storage process of blood
    • Usually mild
    • Occurs more often with multiparous women or multiple transfusions
    • Recurs in 15% of patients
    • Acetaminophen to treat fever or it may be used prophylactically; its use as premedication is controversial, though not harmful
  • Allergic transfusion reaction:
    • Occurs in 1–3% of transfusions
    • Can occur before, during, or after transfusion
    • Usually seen with immunoglobulin A (IgA)–deficient patients
    • Urticaria alone is not a reason to stop transfusion, as long as there are no other signs of anaphylaxis
    • Antihistamine may be used as therapy or prophylactically
  • Premedicating with acetaminophen and diphenhydramine found to have no effect on incidence of transfusion reaction compared with placebo

Delayed Reactions
  • Infection:
    • HIV, hepatitis B, hepatitis C:
      • Blood screened for viruses
      • Blood treated to inactivate viruses
      • Blood donors with recent history of travel or poor health are deferred from donating
    • Bacterial:
      • 5 deaths in 2015
      • S. aureus most common pathogen
  • Delayed extravascular hemolytic reaction:
    • Occurs 7–10 d after transfusion
    • Antigen–antibody reaction that develops after transfusion
    • Coombs test positive
    • Usually asymptomatic, but can present with low-grade fever or jaundice
    • Blood bank analysis detects antibody
  • Electrolyte imbalance:
    • Hypocalcemia: Calcium binds to citrate
    • Hyper/hypokalemia: Citrate metabolized to bicarbonate, which drives potassium intracellularly; prolonged storage of blood may cause hemolysis and hyperkalemia
  • Graft vs. host disease:
    • Fatal in >90%
    • Immunologically competent lymphocytes transfused into immunocompetent host
    • Host unable to destroy new WBCs
    • Donor WBCs recognize host as foreign and attack host's tissues
  • Anaphylactic reaction:
    • Can occur with <10 mL of exposure
    • Generalized flushing, urticaria, laryngeal edema, bronchospasm, profound hypotension, shock, or cardiac arrest
    • Treat with subcutaneous epinephrine, supportive hemodynamic and respiratory care
  • TACO:
    • Symptoms within 6 hr of a transfusion
    • Due to increased circulating volume
    • Around 20% of serious acute transfusion reactions, more common than AHTR, anaphylaxis, and TRALI
    • Can see respiratory distress and hypotension; more commonly seen in patients with CHF
    • Treatment consists of diuretics and ventilator support, i.e., NIPPV
  • TRALI:
    • Symptoms typically begin with 6 hr of transfusion
    • Acute onset of respiratory distress, bilateral pulmonary edema, fever, tachycardia, hypotension, with normal cardiac function
    • Most common cause of fatal transfusion
    • Difficult to distinguish from ARDS and TACO; often misdiagnosed and underreported
    • Provide supportive care
    • Disease is typically self-limited within 96 hr
    • Mortality is 5–10%
    • Diuretics contraindicated

Pediatric Considerations
Blood can be transfused through 22G peripheral catheter under pressure (but <300 mm Hg) with minimal hemolysis

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Basics

Epidemiology

  • A 2007 study found that there are ∼14.6 million blood transfusions per year
  • In 2015 there were 37 deaths in the U.S. fully attributable to transfusion complications
  • Some type of transfusion reaction occurs in 2% of units transfused within 24 hr
  • Noninfectious complications:
    • Febrile nonhemolytic reaction: Most common: Occurs in 0.1–1% of transfusions; more common in kids; platelets 1 in 900
    • Allergic reaction (nonanaphylactic): Common; 1 in 100–1 in 33 transfusions
    • Anaphylaxis: 1 in 20,000–1 in 50,000
    • Acute hemolytic reaction: 1 in 38,000–1 in 70,000; resulting in 5 deaths per 10 million transfusions
    • Delayed hemolytic reaction: 1 in 4,000–1 in 11,000
    • Transfusion-associated circulatory overload (TACO): 1 in 100, but as high as 10% in susceptible populations
    • Alloimmunization: 1 in 10–1 in 100
    • Graft vs. host disease: 1 in 400,000; rare but has >90% mortality
    • Transfusion-related lung injury (TRALI): 1 in 5,000–1 in 190,000; represents 13% of reported transfusion-related deaths
    • Iron overload: Unknown incidence, depends on volume of blood, often occurs after >100 RBC units
    • Hypocalcemia: Unknown incidence
    • Hyperkalemia: Unknown incidence
  • Infectious complications:
    • Bacterial contamination: RBCs 1 in 65,000–1 in 500,000; platelets 1 in 1,000–1 in 10,000:
      • Most common bacterial agents: Yersinia enterocolitica, Pseudomonas spp., Serratia spp., S. aureus
      • Leading cause of mortality among infectious complications; 17–22% of all cases
    • Hepatitis C: 1 in 1.6 million
    • Hepatitis B: 1 in 100,000–1 in 400,000
    • HTLV I and II: 1 in 500,000– 1 in 3 million
    • HIV: 1 in 1.4 million–1 in 4.7 million
    • HAV: 1 in 1,000,000
    • B19 parvovirus: 1 in 40,000; posttransfusion anemia rare with scattered case reports
    • Parasites: Babesia and malaria: <1 in 1 million
    • Parasites: Trypanosoma cruzi: 1 in 42,000
    • Case reports of Epstein–Barr virus, Lyme disease, brucellosis, human herpesvirus, Creutzfeldt–Jakob disease

Acute Intravascular Hemolytic Transfusion Reaction
  • Mortality and morbidity correlate with amount of incompatible blood transfused (symptoms can occur with exposure to as little as 5–20 mL)
  • Usually due to lab error
  • Occurs immediately from:
    • ABO incompatibility (most common)
    • Also from other antigen incompatibility, i.e., Kell, JK
  • Intravascular hemolysis causing activation of coagulation system, leading to inflammation, shock, and DIC
  • Mediators (cytokines) released during inflammatory response
  • Clinically may see chills, fever, hypotension, hemoglobinuria, back pain, and DIC
  • Renal failure:
    • Cytokines cause local release of endothelin in kidney, causing vasoconstriction
    • Leads to parenchymal ischemia and acute renal failure
  • Respiratory failure owing to pulmonary edema/adult ARDS:
    • Free hemoglobin (Hb) causes vasoconstriction in pulmonary vasculature

Other Transfusion-Related Complications
  • Hemolysis because of Rh incompatibility:
    • Mild, self-limiting
    • 1:200 U transfused
  • Febrile nonhemolytic transfusion reaction:
    • Most common transfusion reaction, diagnosis of exclusion
    • Temperature increases at least 1°C with chills within 6 hr
    • Caused by cytokines generated in the storage process of blood
    • Usually mild
    • Occurs more often with multiparous women or multiple transfusions
    • Recurs in 15% of patients
    • Acetaminophen to treat fever or it may be used prophylactically; its use as premedication is controversial, though not harmful
  • Allergic transfusion reaction:
    • Occurs in 1–3% of transfusions
    • Can occur before, during, or after transfusion
    • Usually seen with immunoglobulin A (IgA)–deficient patients
    • Urticaria alone is not a reason to stop transfusion, as long as there are no other signs of anaphylaxis
    • Antihistamine may be used as therapy or prophylactically
  • Premedicating with acetaminophen and diphenhydramine found to have no effect on incidence of transfusion reaction compared with placebo

Delayed Reactions
  • Infection:
    • HIV, hepatitis B, hepatitis C:
      • Blood screened for viruses
      • Blood treated to inactivate viruses
      • Blood donors with recent history of travel or poor health are deferred from donating
    • Bacterial:
      • 5 deaths in 2015
      • S. aureus most common pathogen
  • Delayed extravascular hemolytic reaction:
    • Occurs 7–10 d after transfusion
    • Antigen–antibody reaction that develops after transfusion
    • Coombs test positive
    • Usually asymptomatic, but can present with low-grade fever or jaundice
    • Blood bank analysis detects antibody
  • Electrolyte imbalance:
    • Hypocalcemia: Calcium binds to citrate
    • Hyper/hypokalemia: Citrate metabolized to bicarbonate, which drives potassium intracellularly; prolonged storage of blood may cause hemolysis and hyperkalemia
  • Graft vs. host disease:
    • Fatal in >90%
    • Immunologically competent lymphocytes transfused into immunocompetent host
    • Host unable to destroy new WBCs
    • Donor WBCs recognize host as foreign and attack host's tissues
  • Anaphylactic reaction:
    • Can occur with <10 mL of exposure
    • Generalized flushing, urticaria, laryngeal edema, bronchospasm, profound hypotension, shock, or cardiac arrest
    • Treat with subcutaneous epinephrine, supportive hemodynamic and respiratory care
  • TACO:
    • Symptoms within 6 hr of a transfusion
    • Due to increased circulating volume
    • Around 20% of serious acute transfusion reactions, more common than AHTR, anaphylaxis, and TRALI
    • Can see respiratory distress and hypotension; more commonly seen in patients with CHF
    • Treatment consists of diuretics and ventilator support, i.e., NIPPV
  • TRALI:
    • Symptoms typically begin with 6 hr of transfusion
    • Acute onset of respiratory distress, bilateral pulmonary edema, fever, tachycardia, hypotension, with normal cardiac function
    • Most common cause of fatal transfusion
    • Difficult to distinguish from ARDS and TACO; often misdiagnosed and underreported
    • Provide supportive care
    • Disease is typically self-limited within 96 hr
    • Mortality is 5–10%
    • Diuretics contraindicated

Pediatric Considerations
Blood can be transfused through 22G peripheral catheter under pressure (but <300 mm Hg) with minimal hemolysis

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