Febrile non-haemolytic transfusion reaction

Overview

Febrile non-haemolytic transfusion reaction (FNHTR) is the most common acute transfusion reaction. It is benign and self-limiting, but must be distinguished promptly from acute haemolytic reaction and bacterial contamination.

Pathophysiology

•Immunological: recipient alloantibodies (anti-HLA/anti-HNA) bind donor leucocytes → cytokine release (IL-1, IL-6, TNF-alpha) → hypothalamic PGE2 → fever

•Non-immunological (platelets): pre-formed cytokines accumulate in stored platelet concentrates during storage → infused directly into recipient

•No haemolysis, no red cell antibody attack, no infection

Risk factors

Presentation

•Onset during or within 1-2 hours of transfusion (up to 4 hours post-completion)

•Fever - rise >1°C from baseline or new temperature >38°C (hallmark)

•Rigors - shaking chills

•Flushing, headache, malaise, mild tachycardia

•No hypotension, no haemoglobinuria, no back/loin pain, no haemodynamic compromise

⚠️

FNHTR is a diagnosis of exclusion - fever during transfusion MUST trigger exclusion of acute haemolytic reaction and bacterial contamination before attributing to FNHTR.

Investigations

Investigations aim to exclude serious differentials, not confirm FNHTR (which is a clinical diagnosis).

•Urine inspection - pink/red urine = haemoglobinuria → suggests haemolysis

•Repeat blood group, crossmatch + direct antiglobulin test (DAT) - exclude ABO incompatibility

•Blood cultures (patient and blood bag) - exclude bacterial contamination

•Haemolysis screen - FBC, LDH, bilirubin, haptoglobin; raised LDH/bilirubin + low haptoglobin = haemolysis

•U&Es - AKI may complicate haemolytic reaction but not FNHTR

Management

Step 1 · Immediate

1. 1Stop the transfusion immediately
2. 2Keep IV line patent with normal saline
3. 3Check observations - BP, HR, SpO2, temperature

↓

Step 2 · Exclude serious causes

1. 1Inspect urine for haemoglobinuria
2. 2Send repeat group & crossmatch, DAT, haemolysis screen, blood cultures (patient + bag)
3. 3Return blood product to blood bank for inspection and culture

↓

Haemolysis or bacterial contamination suspected

Do NOT restart - manage as acute haemolytic reaction or septic transfusion reaction

Serious causes excluded - confirmed FNHTR

Give paracetamol 1 g orally; monitor until fever resolves; transfusion may be restarted with a fresh unit under close observation after reaction settles

↓

Step 3 · Documentation

1. 1Document reaction and report to SHOT (Serious Hazards of Transfusion) haemovigilance scheme

Prevention

•Universal leucodepletion - standard in UK since 1999 for all red cell and platelet concentrates; removes >99.9% donor white cells; single most effective prevention strategy

•Washed blood products - removes residual plasma proteins and cytokines; used in patients with recurrent severe FNHTR

•Pre-medication with *paracetamol - only in patients with documented recurrent FNHTR after haematology discussion; not routine

•Restrictive transfusion thresholds - Hb 70-80 g/L in most non-cardiac adults (NICE) reduces cumulative sensitisation

⚠️

Do not give paracetamol pre-medication routinely before every transfusion - it can mask fever and delay recognition of a more serious reaction.

Prognosis

•Fever and rigors typically resolve within 1-2 hours of stopping transfusion and giving antipyretics

•No haemolysis, no renal impairment, no long-term sequelae

•Main risk is delayed recognition of a concurrent haemolytic reaction, not FNHTR itself