Febrile nonhemolytic transfusion reactions (FNHTR)

Ready to upload
Record number: 
Adverse Occurrence type: 
MPHO Type: 
Estimated frequency: 
2.4 per 1000 transfusions
Time to detection: 
During transfusion or within 4 hours of transfusion completion
Alerting signals, symptoms, evidence of occurrence: 
Fever (>=38°C and a change of >= 1°C from the pretransfusion value); Chills; Sensation of cold or rigors. Symptoms may be accompanied by headache or nausea and disturbances occur during or within 4 hours of transfusion completion. FNHTR is a diagnosis of exclusion, which requires that alternatives be deemed less likely from the available charting or investigative evidence (e.g., hemolytic transfusion reaction, bacterial contamination, or underlying condition).
Demonstration of imputability or root cause: 
The relationship of the adverse event to the transfusion and the likelihood of FNHTR were both determined after review by the Transfusion Safety Officer and transfusion medicine physician. Both of these variables were qualitatively ranked on a certainty scale ranging from definite to doubtful by assessing alternative explanations. These included microbial cultures, patient investigations for other causes of fever (e.g., chest radiograph to rule out pneumonia), pre-existing neutropenia and the duration thereof (as a risk for febrile neutropenia), and other transfusion reactions in which a fever may be a clinical manifestation. The severity of the FNHTR was determined by the clinical status of the patient, the medical interventions required, and disposition changes (unplanned admission to the hospital or stay prolongation).
Imputability grade: 
2 Probable
Groups audience: 
Reference attachment: 
Suggest references: 
Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions. TRANSFUSION 2017;57;1674–1683Ide. Y, Yanagisawa R, Kobayashi J, Komori K, Matsuda K, Amano Y, Nakazawa Y, Takeshita T, Sakashita K, Tozuka M. Relationship between allergic sensitisation-associated single-nucleotide polymorphisms and allergic transfusion reactions and febrile non-haemolytic transfusion reactions in paediatric cases. Blood Transfus. 2022 Mar;20(2):94-102. doi: 10.2450/2021.0230-20. Epub 2021 Feb 3. PMID: 33539286; PMCID: PMC8971021.
This is quite a straightforward retrospective study on a fair number of FNHTR cases. It may not be an innovative study, but it adds to the knowledge base on this often non-severe adverse event that absorbs resources. I have added a study from Japanese colleagues who tried correlating FNHTR and Allergic Reactions to specific single nucleotide polymorphisms (SNPs) in an attempt to clarify the causes of both types of reactions. Please note: there are multiple entries for FNHTR in Notify library: https://www.notifylibrary.org/adverse-incident/febrile-reaction. This entry (1976) might be considered a duplicate and all FNHTRs entries could be reorganized into incident per specific blood product (RBC or PLT)
Expert comments for publication: 
This is a retrospective study carried out in four hospitals in the Toronto area between 2013 and 2015. The authors searched through two hemovigilance databases and identified all known (possible or definite) cases of FNHTR. All blood products were leukoreduced prestorage. Out of 178,730 blood products considered high-risk for FNHTRs, 437 events in 407 unique patients were reported. Though FNHTR is not considered a severe adverse event, the authors underline the burden of postreaction clinical activity in addition to the disturbance itself and conclude that efforts to avoid this adverse event may save resources, reduce patient distress, and encourage compliance with more restrictive transfusion strategies. By product type, FNHTRs were most frequently observed with platelets-only (0.25%), followed by red blood cells-only (0.17%) and intravenous immunoglobulin (IVIG).