Febrile non‑haemolytic transfusion reactions (FNHTR)

Notes

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.

Notes

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.