What is the cause of fever and itching in a patient during a blood transfusion?

Causes of Fever and Itching During Blood Transfusion

Primary Causes

Fever during transfusion most commonly indicates either a febrile non-hemolytic transfusion reaction (FNHTR) from residual leukocytes, or potentially life-threatening bacterial contamination, particularly with platelet products, while itching signals an allergic reaction to plasma proteins or donor allergens. 1, 2

Fever-Specific Etiologies

Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

• Caused by residual leukocytes in blood components releasing inflammatory cytokines during storage and transfusion 3
• Most common transfusion reaction overall, accounting for the majority of fever presentations (63.6% of acute reactions in one large series) 4
• Leukoreduction has dramatically reduced but not eliminated this complication 5, 3

Bacterial Contamination

• Critical to recognize: Bacterial contamination should be suspected if patients experience severe febrile reactions either during or shortly after platelet transfusions 5
• Fever within 6 hours after platelet transfusion is a leading cause of transfusion-related mortality 1
• Platelets stored at room temperature (20-24°C) provide ideal bacterial growth conditions, making them the highest-risk component 5
• May present with isolated fever initially, masking the severity until hemodynamic collapse occurs 1

Acute Hemolytic Transfusion Reaction

• Fever accompanied by hypotension, tachycardia, back pain, or dark urine suggests hemolysis 1, 6
• Results from ABO incompatibility or other red cell antibodies 4

Itching-Specific Etiologies

Allergic Transfusion Reactions

• Account for approximately 17% of all transfusion reactions, occurring in roughly 1 in 4,124 blood components transfused 7
• Caused by recipient IgE antibodies reacting to plasma proteins in the donor blood 2
• Recent evidence suggests immunologically active food allergens from donor blood can transfer to allergic recipients, triggering reactions 2
• Platelets represent the main source of allergic hazards due to processing/storage lesions and platelet physiology itself 3

Clinical Presentation Variability

• While urticaria and pruritus are classic, 9.5% of allergic reactions present without skin manifestations 7
• Severe allergic reactions (anaphylaxis) occur in approximately 1 in 30,281 transfusions 7
• Can occur even with autologous blood transfusions (5 cases documented in one series) 7

Combined Fever and Itching

When both symptoms occur together, consider:

• Severe allergic reaction progressing toward anaphylaxis - requires immediate epinephrine administration 1, 8
• Bacterial contamination with concurrent allergic component - particularly dangerous in neutropenic patients where fever may be masked by scheduled antipyretics 1
• Multiple simultaneous reaction types can occur, making clinical assessment critical 7

Critical Diagnostic Distinctions

Immediate risk stratification is essential:

• Fever + hypotension/tachycardia = hemolytic reaction or septic transfusion (life-threatening) 1
• Fever + respiratory symptoms within 1-6 hours = possible TRALI (top three cause of transfusion deaths) 1, 6
• Itching + wheezing/respiratory distress = anaphylaxis requiring epinephrine 8
• Isolated fever or itching without hemodynamic changes = likely FNHTR or mild allergic reaction 1, 4

Pathophysiology Summary

Fever mechanisms:

• Cytokine release from residual donor leukocytes (IL-1, IL-6, TNF-α) 3
• Bacterial endotoxins from contaminated products 5
• Complement activation in hemolytic reactions 4
• Microparticle emission during storage causing pro-inflammatory responses 3

Itching mechanisms:

• Mast cell degranulation releasing histamine in response to plasma proteins 2
• Transfer of donor food allergens to sensitized recipients 2
• IgE-mediated hypersensitivity reactions 2, 7

Prevention Considerations

• Leukoreduction has substantially reduced FNHTR incidence but cannot eliminate it entirely 5, 3
• Washed platelets can prevent allergic reactions but result in 15-55% platelet loss 5
• Routine premedication with acetaminophen and diphenhydramine has failed to prevent transfusion reactions in studies and may mask early warning signs of serious complications 9
• Bacterial detection methods and pathogen reduction technologies can extend platelet storage safety 5