Febrile Non-Haemolytic Transfusion Reaction

Febrile non-haemolytic transfusion reaction (FNHTR) is the most common transfusion reaction. Its needs to be differentiated from haemolytic transfusion reaction and bacterial contamination both of which are serious and potentially fatal. FNHTR on the other hand causes morbidity but is not fatal.

Pathogenesis

The causes of FNHTR are:

1. Transfusion of leukocyte antigens that result in a cytokine release from recipient lymphocytes leading to symptoms.
2. Transfusion of cytokines that accumulate in the transfused unit with storage. The cytokine concentration in blood components increases with leukocyte count and duration storage. Platelet concentrates are implicated in FNHTR more than any other product. The incidence of FNHTR increases with age of platelet concentrate (Transfusion 1993; 33:794-7) and leukocyte count of platelet concentrate (N Engl J Med. 1994 Sep 8;331(10):625-8). Duration of storage co-relates more with FNHTR than leukocyte count.                                                                                                                                                                                                                                                                                                                                                                                                                                                   

Incidence of FNHTR

The risk of FNHTR varies with the product and how the product is processed. A retrospective analysis has reported FNHTR to be complicating 0.34% of red cell and 2.18% of platelet transfusions. Platelet concentrates are associated with the highest incidence of FNHTR because

1. Platelet concentrates have a higher concentration of leucocytes.
2. They are stored at room temperature which allows a greater accumulation cytokines 
3. A patient is receives transfusion from multiple donors increasing antigenic diversity of transfused leucocytes  

Pre-storage leukodepletion reduces the risk of FNHTR significantly. A large retrospective analysis showed that leukodepletion decreased the risk of FNHTR following RBC transfusion by 47% from 0.34% to 0.18% and following platelet transfusion by 93%, from 2.18% to 0.15% (Transfusion 2004:44;25-29).

Clinical Presentation

FNHTR presents with fever (rise in temperature by more than 1℃) during or within a few hours of transfusion. Fever is accompanied by chills, rigours and headache. The manifestations of FNHTR are non-specific and are shared by acute haemolytic transfusion reactions and bacterial contamination. Unlike FNHTR both may be fatal and FNHTR needs to be differentiated from the two.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

Diagnosis

Fever after initiating a blood component is not specific to FNHTR. There are no tests specific for FNHTR and the diagnosis is made by exclusion. The investigations in case of suspected FNHTR include:

1. Tests to exclude haemolytic transfusion reaction: Direct anti-globulin test on the post-transfusion blood sample and pre-transfusion blood sample is available. Donor grouping and donor and recipient cross matching must be performed. 
2. Tests to exclude bacterial contamination: Gram staining and culture should be performed.

Management

1. Stop transfusion, maintain a venous line, observe the patient closely.  
2. Collect post-transfusion blood specimen. Send the sample along with the unit being transfused and the transfusion set to the blood bank with a summary of clinical observations.
3. Do not transfuse the unit even if haemolytic transfusion reaction is excluded because there is no rapid test to exclude bacterial contamination.
4. Drugs: Paracetamol is usually effective. Though antihistamines are indicated only in presence of allergy (pruritus and rash), they are often administered irrespective as is hydroicortisone. Meperidine terminates severe rigours. It is contraindicated in renal failure and patient taking mono-amine oxidase (MAO) inhibitors. There is a risk of accumulation normeperidine in patients with renal failure. Normeperidine can cause seizures. Patients with MAO inhibitors are at risk of the serotonin syndrome.

Prevention

1. Premediacation with paracetamol and antihistamines with or without hydrocortisone reduce the risk of FNHTR. 
2. Slowing the rate of infusion may be effective. 
3. Pre-storage leukodepletion (Blood Transfus 2016:14:2124-227), as has been discussed above, decreases the risk of FNHTR but post-storage leukodepeltion is not effective. 
4. Apheresis platelets are collected from a single individual and are nor stored. They are associated with a lower risk of FNHTR.

See Also

Guideline on the investigation and management of acute transfusion reactions Prepared by the BCSH Blood Transfusion Task Force. British Journal of Haematology, 2012, 159, 143–153