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

• 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

• 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

• 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