What is the most likely blood transfusion reaction in a patient who develops pain at the intravenous (IV) site, difficulty breathing, and fever after 10 minutes of blood transfusion?

Acute Hemolytic Transfusion Reaction (Answer: D)

The clinical triad of pain at the IV site, difficulty breathing, and fever occurring within 10 minutes of blood transfusion is most consistent with an acute hemolytic transfusion reaction, which represents a medical emergency requiring immediate cessation of transfusion. 1, 2

Clinical Reasoning

The timing and symptom constellation are critical diagnostic clues:

• Pain at the cannula site is a pathognomonic early sign of acute hemolytic reaction, caused by complement activation and cytokine release at the site of incompatible blood entry 3
• Onset within 10 minutes strongly favors acute hemolytic reaction over other diagnoses, as this reaction occurs during or within 24 hours of transfusion, typically manifesting within the first 15 minutes 4, 3
• Difficulty breathing results from the systemic inflammatory response syndrome triggered by intravascular hemolysis, with complement cleavage products (C3a, C5a) causing vasomotor disturbances and respiratory compromise 3
• Fever accompanies the acute hemolytic process due to cytokine release and the inflammatory cascade 1, 3

Why Other Options Are Less Likely

Febrile Non-Hemolytic Reaction (Option A):

• Presents with isolated fever and chills without the characteristic pain at the IV site 1, 5
• Lacks the acute respiratory distress and hemodynamic instability seen in this patient 5
• While common (1.1-2.15% incidence), it does not explain the full clinical picture 1

Allergic Reaction (Option C):

• Typically manifests with urticaria, pruritus, and skin flushing rather than IV site pain 1
• Respiratory symptoms in allergic reactions are usually due to bronchospasm or laryngeal edema, not the acute dyspnea from systemic inflammation 1
• Fever is not a primary feature of allergic transfusion reactions 5

TRALI Consideration:

• While TRALI causes respiratory distress, it typically occurs 1-2 hours after transfusion, not within 10 minutes 6, 2
• TRALI presents with hypoxemia and non-cardiogenic pulmonary edema but lacks the characteristic IV site pain 6

Pathophysiology of Acute Hemolytic Reaction

The clinical manifestations result from multiple pathophysiological cascades:

• Complete complement activation leads to intravascular hemolysis with formation of anaphylatoxins (C3a, C5a) 4, 3
• Cytokine release causes systemic inflammatory response syndrome with fever, hypotension, and respiratory distress 4
• Activation of the kinin system produces vasodilation and the sensation of pain 3
• Intrinsic clotting cascade activation can progress to disseminated intravascular coagulation and renal failure if not immediately addressed 4, 3

Immediate Management Protocol

Stop the transfusion immediately and maintain IV access with normal saline—this is the single most critical intervention 2, 5

Assess hemodynamic status:

• Monitor vital signs every 5-15 minutes including heart rate, blood pressure, temperature, respiratory rate, and oxygen saturation 2
• Administer high-flow oxygen to address hypoxemia 2
• Maintain mean arterial pressure >65-70 mmHg with IV fluid resuscitation 2

Obtain urgent laboratory studies:

• Send the blood component bag with administration set back to the transfusion laboratory 5
• Collect post-reaction blood samples for repeat crossmatch, direct antiglobulin test (Coombs), complete blood count, PT, aPTT, fibrinogen 2, 5
• Visual inspection of plasma for hemolysis and urine analysis for hemoglobinuria 5
• Blood cultures if bacterial contamination is suspected 5

Renal protection:

• Aggressive fluid resuscitation to maintain urine output >100 mL/hour to prevent acute tubular necrosis from hemoglobinuria 5

Critical Pitfalls to Avoid

• Never continue the transfusion even if symptoms seem mild, as the reaction will worsen with continued exposure 5
• Do not assume this is a simple febrile reaction based on fever alone—the IV site pain and respiratory distress indicate a more serious process 5
• Verify patient identification and blood component compatibility immediately, as clerical errors are the most common cause of acute hemolytic reactions 2, 5
• Do not delay notification of the transfusion laboratory/blood bank, as this affects both immediate patient management and future transfusion safety 2, 5

The risk of acute hemolytic transfusion reactions is approximately 1:70,000 per unit, with an estimated mortality risk of 1:1,250,000 RBC units transfused 1, 4. However, when they occur, rapid recognition and immediate intervention are essential to prevent progression to disseminated intravascular coagulation, renal failure, and shock 4, 3.