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Febrile non‑haemolytic transfusion reactions (FNHTR)

2011–12 Data Summary (n=320)
Age   Sex   Day of Transfusion  
0–4 years 5 Male 114 Week day 246
5–14 years 7 Female 93 Weekend 74
15–24 years 7 Uncategorised 113    
25–34 years 15 Facility Location   Time of Transfusion  
35–44 years 18 Major City 162 Between 7am and 7pm 92
45–54 years 28 Inner Regional 47 Between 7pm and 7am 32
55–64 years 45 Outer Regional 7 Unknown 196
65–74 years 70 Remote 1    
75+ years 122 Very Remote    
Not specified 3 Uncategorised 103    
Clinical Outcome Severity   Imputability   Blood Component  
Death Excluded/Unlikely 20 Whole blood
Life threatening 1 Possible 90 Red cells 294
Severe morbidity 8 Likely/Probable 182 Platelets 26
Minor morbidity 306 Confirmed/Certain 5 Fresh Frozen Plasma
No morbidity 4 Not assessable 23 Cryoprecipitate
Outcome not available 1     Cryodepleted plasma
2012–13 Data Summary (n=231)
Age   Sex   Day of Transfusion  
0–4 years 3 Male 62 Week day 178
5–14 years 6 Female 49 Weekend 53
15–24 years 8 Uncategorised 120    
25–34 years 12 Facility Location   Time of Transfusion  
35–44 years 21 Major City 112 Between 7am and 7pm 15
45–54 years 27 Inner Regional Between 7pm and 7am 10
55–64 years 36 Outer Regional 4 Unknown 206
65–74 years 54 Remote    
75+ years 58 Very Remote    
Not specified 6 Uncategorised 115    
Clinical Outcome Severity   Imputability   Blood Component  
Death Excluded/Unlikely 4 Whole blood 1
Life threatening Possible 123 Red cells 201
Severe morbidity 12 Likely/Probable 83 Platelets 24
Minor morbidity 202 Confirmed/Certain Fresh Frozen Plasma 5
No morbidity 9 Not assessable 21 Cryoprecipitate
Outcome not available 8     Cryodepleted plasma


  1. QLD data is unavailable for 2012–13.
  2. Sex and facility location data is unavailable for NSW.
  3. Time of transfusion data is unavailable for NSW and SA.
  4. Data is unavailable for WA.
  5. Uncategorised refers to those reports where no data was provided.

FNHTR (see Appendix II: Definitions in haemovigilance) is the most common transfusion-related adverse event reported in Australia. The incidence rates for FNHTR have been reported at less than 1% with current methods that use single‑donor apheresis units and leucoreduced products.[8],[9] In combined financial years 2011–12 and 2012–13, 551 FNHTRs were reported to the National Haemovigilance Program, accounting for more than half (52.8%) of the total reports (1,044) for this period.

In the five financial years to 2012–13:

  • The number of FNHTRs more than doubled, from 154 in 2008–09 to 321 in 2010–11 and 320 in 2011–12, mainly due to increased reporting of this event from NSW, QLD and SA. The number of FNHTRs dropped in 2012–13 due to the unavailability of QLD data.
  • Despite the increase in the number of reported FNHTRs, the number of cases reporting life threatening severity dropped from five in 2008‑09 to one (imputability=likely/probable) in 2011–12 and zero in 2012–13.
  • The number of reports of minor morbidity had an increase from 14 in 2008–09 to 306 in 2011‑12. This may indicate an increased awareness of collecting and reporting FNHTR events at a hospital level and a state level, and inclusion of NSW data. The number dropped in 2012–13, due to the unavailability of QLD data.
  • The number of reports of outcome not available dropped from 55 in 2008–09 to 1 in 2011‑12 and 8 in 2012–13.
  • The majority of cases were related to red cell transfusion.

The lack of SA and NSW data for transfusion time and NSW data for sex and facility location contributed to the increased numbers of unknown/uncategorised cases for these categories in 2011–12 and 2012–13.

In the period 2011–12 and 2012–13, around 49.0% of FNHTRs (270) were assigned an imputability score of likely/probable or confirmed/certain, including 12 cases with severe morbidity and one case with life threatening severity.

Table 7: FNHTR clinical outcome severity by imputability, 2011–12 and 2012–13
Clinical Outcome Severity Imputability Total
  Excluded / Unlikely Possible Likely / Probable Confirmed / Certain N/A /Not assessable  
Life threatening            
2011–12 - - 1 - - 1
2012–13 - - - - - -
Severe morbidity            
2011–12 - 3 5 - - 8
2012–13 - 5 7 - - 12
Minor morbidity            
2011–12 20 85 174 5 22 306
2012–13 4 106 72 - 20 202
No morbidity            
2011–12 - 2 2 - - 4
2012–13 - 5 4 - - 9
Outcome not available            
2011–12 - - - - 1 1
2012–13 - 7 - - 1 8
Total 24 213 265 5 44 551


  1. Outcome severity and imputability data unavailable for QLD for 2012–13.
  2. Outcome severity and imputability data unavailable for WA.

The current definition of FNHTR used by the HAC aligns with the definitions used by the IHN and the ISBT Working Party on Haemovigilance. However, there is still some divergence between the definitions in use. The VIC STIR system uses a higher temperature threshold than specified by the ANHDD; STIR specifies a fever >38.5°C or a change of 1.5°C above baseline to reflect more severe adverse events. This STIR definition matches that of the New Zealand Blood National Haemovigilance Programme. This results in some FNHTR incidents that are reportable to the National Haemovigilance Program being screened out by STIR.

Clinically confounding factors may complicate diagnosis and reporting of FNHTR. Difficulties with diagnosis and the burden of reporting for this common event may justify higher reporting thresholds. The ISBT suggests that for the purpose of international comparisons, only the most severe cases of FNHTR should be reported (fever ≥39°C oral or equivalent and a change of ≥2°C from pre‑transfusion value; chills/rigors).

Clinical recommendation

The ANZSBT Guidelines for the Administration of Blood Products recommends that a temperature rise to ≥38°C or ≥1°C above baseline (if baseline ≥37°C) should prompt the interruption (stopping) of the transfusion and a clinical assessment of the patient.[10]

The Blood Service provides guidance on the recognition, investigation and management of FNHTR.[11]

  • When to suspect this adverse reaction?

    Patients present with an unexpected temperature rise (≥38°C or ≥1°C above baseline, if baseline ≥37°C) during or shortly after transfusion. This is usually an isolated finding. Occasionally the fever is accompanied by chills.

    Chills, rigors, increased respiratory rate, change in blood pressure, anxiety and a headache may accompany this reaction but occur in several more serious transfusion reactions also, the most serious being acute haemolytic reaction, transfusion associated sepsis and TRALI. FNHTR is a diagnosis of exclusion. This occurs in 0.1% to 1% of transfusions with leucocyte depletion.

  • Usual causes?

    Cytokine accumulation during storage of cellular components (especially in platelet units) is thought to be the most common event leading to symptoms of FNHTRs. Cytokines are released by white cells and pre-storage leucodepletion has reduced this risk.

    FNHTR is also caused by the presence of recipient antibodies (raised as a result of previous transfusions or pregnancies) reacting to donor human leucocyte antigens (HLA) or other antigens. These antigens are present on donor lymphocytes, granulocytes, or platelets.

  • Investigation

    Clinically assess the transfused patient for fever, chills, rigors and headache.

    Acute haemolytic reaction may need exclusion.

    Direct antiglobulin test (DAT), blood count and repeat ABO grouping may be indicated.

    Consider investigations for transfusion associated sepsis.

    In patients with repeated FNHTR, investigation for HLA antibodies may be useful.

  • What to do?

    Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.

    Treat the fever with an antipyretic. However, avoid aspirin in thrombocytopenic and paediatric patients.

    Consider and exclude other causes, as fever alone may be the first manifestation of a life threatening reaction.

    Rule out acute haemolytic reaction, transfusion associated sepsis and TRALI.

    Recommencement of the transfusion, at a slow rate, is possible if other causes of a fever have been excluded.