What is the treatment for febrile illness associated with transfusions?

Treatment of Febrile Illness Associated with Transfusions

For febrile non-hemolytic transfusion reactions (FNHTR), immediately stop the transfusion, administer acetaminophen 650-1000 mg IV or orally for symptomatic relief, rule out more serious transfusion reactions through clinical assessment and laboratory testing, and prevent future reactions by using leukocyte-reduced blood products. 1, 2

Immediate Management When Fever Develops

• Stop the transfusion immediately and maintain IV access with normal saline—this is the single most critical intervention that can prevent progression to severe complications 1, 2

• Notify the blood bank immediately to report the reaction and initiate investigation 1, 2

• Monitor vital signs every 5-15 minutes including heart rate, blood pressure, temperature, respiratory rate, and oxygen saturation 2

• Obtain blood cultures immediately after onset of fever using proper technique and adequate volume, especially in neutropenic or immunocompromised patients 1

Pharmacologic Treatment

• Administer acetaminophen 650-1000 mg IV (for adults ≥50 kg) or 15 mg/kg IV (for adults <50 kg and children) over 15 minutes for fever control 3

• Alternative oral acetaminophen dosing is acceptable if IV access is limited, with maximum daily dose of 4000 mg for adults ≥50 kg or 75 mg/kg for those <50 kg 3

• Initiate empiric broad-spectrum antibiotics if infection is suspected, particularly in neutropenic patients with profound granulocytopenia (<100/mm³) 4

Differential Diagnosis to Rule Out

Critical distinction: FNHTR is a diagnosis of exclusion—you must first rule out life-threatening transfusion reactions that present with fever:

• Acute hemolytic transfusion reaction: Check for hemoglobinuria, falling hemoglobin, elevated LDH and indirect bilirubin, positive direct antiglobulin test 2

• Bacterial contamination: Obtain blood cultures from the patient and the blood product bag; this can present with high fever, rigors, and rapid progression to septic shock 2

• TRALI (Transfusion-Related Acute Lung Injury): Assess for dyspnea, hypoxemia, and bilateral pulmonary infiltrates within 6 hours of transfusion 2

• TACO (Transfusion-Associated Circulatory Overload): Look for hypertension, elevated BNP, pulmonary edema, and jugular venous distension 2

Diagnostic Workup

• Obtain post-reaction blood samples including repeat crossmatch, complete blood count, coagulation studies, and blood cultures 2

• Send the blood component bag with administration set to the transfusion laboratory for analysis 2

• Double-check all documentation for administration errors, particularly patient identification and blood component compatibility 2

• Consider procalcitonin testing to discriminate between infectious and non-infectious causes of fever 1

Prevention of Future Reactions

• Use leukocyte-reduced blood products for all subsequent transfusions—this significantly reduces FNHTR incidence from approximately 20% to <1% 5, 6

• For patients with recurrent FNHTR despite leukocyte reduction, consider saline-washed platelets which remove cytokines accumulated during storage 5

• Do NOT routinely premedicate with acetaminophen or diphenhydramine—evidence shows no benefit and possible increased reaction rates (odds ratio 1.74 for both medications) 7

• Use single-donor apheresis platelets rather than pooled concentrates when possible, as they reduce reaction rates from 21.4% to 8.4% 8

When to Resume Transfusion

• Resume transfusion only after fever resolves and serious transfusion reactions (hemolytic reaction, bacterial contamination, TRALI, TACO) are ruled out through appropriate testing 1

• If infection is identified and appropriately treated, transfusion may resume once the patient is clinically stable 1

• Consider slower transfusion rates when resuming to allow for closer monitoring 1

Common Pitfalls to Avoid

• Do not proceed with transfusion despite fever—fever may mask signs of a serious transfusion reaction or be misinterpreted as a simple FNHTR when it represents bacterial contamination or hemolysis 1

• Do not delay blood cultures—obtain cultures before starting antibiotics whenever possible, as this is critical for identifying bacterial contamination of blood products 1

• Do not assume all febrile reactions are benign FNHTR—maintain high suspicion for infection regardless of cell count in immunocompromised patients 1

• Do not routinely use prophylactic antipyretics—this practice is not supported by evidence and may mask important clinical signs 7

Special Populations

Neutropenic patients (absolute neutrophil count <500/mm³):

• Empirical broad-spectrum antimicrobial therapy is mandatory for fever 4
• Prophylactic fluoroquinolones may be appropriate for expected prolonged profound granulocytopenia (<100/mm³ for ≥2 weeks) 4
• Serial surveillance cultures help detect resistant organisms 4

Pediatric patients:

• Acetaminophen dosing: 15 mg/kg IV every 6 hours (maximum 15 mg/kg per dose, 75 mg/kg per day) for children 2-12 years 3
• For infants 29 days to 2 years: 15 mg/kg every 6 hours (maximum 60 mg/kg per day) 3
• For neonates ≥32 weeks gestational age up to 28 days: 12.5 mg/kg every 6 hours (maximum 50 mg/kg per day) 3