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1
Question:

A 16-year-old boy comes to the emergency department due to a dirt bike collision.  Trauma evaluation reveals a femur fracture, and the patient undergoes open reduction and internal fixation.  He receives a packed red blood cell transfusion postoperatively.  Five minutes after the transfusion begins, the patient acutely develops chills and severe flank pain.  Temperature is 39.1 C (102.4 F), blood pressure is 88/40 mm Hg, pulse is 130/min, and respirations are 30/min.  Physical examination shows bleeding around the intravenous catheter site.  Breath sounds are normal.  Which of the following is the most likely cause of this patient's transfusion reaction?

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Explanation:

Immunologic blood transfusion reactions

Transfusion reaction

Onset*

Cause

Key features

Anaphylactic

Within seconds to minutes

Recipient anti-IgA antibodies directed against donor blood IgA

  • Angioedema, hypotension, respiratory distress/wheezing,
    shock
  • IgA-deficient recipient

Acute hemolytic

Within
1 hr

ABO incompatibility (often clerical error)

  • Fever, flank pain, hemoglobinuria
  • Disseminated intravascular coagulation
  • Positive Coombs test

Febrile nonhemolytic (most common reaction)

Within
1-6 hr

Cytokine accumulation during blood storage

  • Fever & chills

Urticarial

Within
2-3 hr

Recipient IgE against blood product component

  • Urticaria

Transfusion-related acute lung injury

Within
6 hr

Donor anti-leukocyte antibodies

  • Respiratory distress
  • Noncardiogenic pulmonary edema with bilateral pulmonary infiltrates

Delayed hemolytic

Within days to weeks

Anamnestic antibody response

  • Often asymptomatic
  • Laboratory evidence of hemolytic anemia
  • Positive Coombs test, positive new antibody screen

Graft versus host

Within weeks

Donor T lymphocytes

  • Rash, fever, gastrointestinal symptoms, pancytopenia

*Time after transfusion initiation.

This patient likely has an acute hemolytic transfusion reaction, a rare but life-threatening reaction typically caused by transfusion of mismatched blood (ie, ABO incompatibility), secondary to clerical error.  Pathogenesis involves recipient antibodies reacting with donor blood antigens, causing complement fixation and hemolysis as well as a proinflammatory reaction.

Therefore, patients develop fever, chills, and hypotension within 1 hour after transfusion initiation; nonspecific flank pain is also characteristic.  Hemolysis causes hemoglobinuria and may lead to acute renal failure (due to acute tubular necrosis), disseminated intravascular coagulation (eg, bleeding from intravenous site, as in this patient), and shock.  Key laboratory findings include a positive direct Coombs test; pink or dark brown plasma and urine (due to hemolysis); and a repeat type and crossmatch confirming a mismatch.

Management includes immediate cessation of transfusion, aggressive intravenous fluid administration, and supportive care.

(Choice B)  Delayed hemolytic transfusion reactions result from an anamnestic antibody response to a red blood cell antigen to which the patient was previously sensitized (eg, pregnancy).  In contrast to this case, patients typically develop extravascular hemolysis days to weeks after transfusion.

(Choice C)  Transfusion-transmitted bacterial infection (TTBI), due to bacterial contamination of blood products, is characterized by fever, tachycardia, and hypotension around 30 minutes after transfusion completion.  Flank pain is not associated with TTBI.  In addition, TTBI most commonly occurs with platelet (rather than red blood cell) transfusions because platelets are stored at room temperature, which increases their susceptibility to bacterial growth.

(Choice D)  Febrile nonhemolytic transfusion reaction is a common, benign reaction that occurs within 1-6 hours after transfusion due to the release of accumulated cytokines in stored blood.  Patients develop transient fever and chills.  Hypotension and flank pain do not occur.

(Choice E)  Individuals with IgA deficiency are at risk of developing anaphylactic reaction to blood products due to preformed anti-IgA antibodies (IgE or IgG) that react against donor blood IgA.  Angioedema, hypotension, and respiratory distress (eg, wheezing) occur within minutes after transfusion initiation.  This patient's fever and lack of wheezing or rash make anaphylaxis less likely.

Educational objective:
Acute hemolytic transfusion reaction is an uncommon, life-threatening reaction due to transfusion of mismatched blood (eg, ABO incompatibility), which causes fever, flank pain, and hemoglobinuria within 1 hour of transfusion initiation.  Continued hemolysis can lead to acute renal failure, disseminated intravascular coagulation, and shock.