Febrile and Allergic Reactions

Febrile non-haemolytic, allergic and anaphylactic reactions are the commonest transfusion reactions. They differ in severity from a nuisance to a medical emergency, and the first task is to exclude a serious cause before accepting a mild label.

Febrile non-haemolytic transfusion reaction. Temperature of 38 degrees Celsius or over with a rise of 1 degree Celsius or more from baseline, with or without chills and rigors, during or within about 4 hours of transfusion, without another cause. It is commoner with platelets and in patients who have had many transfusions, and is mediated by cytokines or recipient antibodies to donor leucocytes. It is a diagnosis of exclusion.

Allergic reaction. Urticaria, itch, flushing, localised angioedema or mild wheeze, within minutes to 4 hours, caused by recipient antibodies to donor plasma proteins.

Anaphylactic reaction. Rapid onset of airway swelling, bronchospasm, stridor, hypotension, collapse, gastrointestinal symptoms with skin signs, usually within minutes of starting. Causes include IgA deficiency with anti-IgA, haptoglobin deficiency, antibodies to other plasma proteins and, rarely, to drugs or allergens in the donor plasma.

Severity.

• Mild: isolated skin signs or fever with a rise under 2 degrees Celsius.

• Moderate: generalised urticaria, rigors, mild dyspnoea, fever with rise of 2 degrees Celsius or more.

• Severe: airway, breathing or circulation compromise.

Special groups. Children, patients with many previous transfusions, patients with IgA deficiency, and those with a history of reactions.

Differential diagnosis.

• Fever with rigors: acute haemolytic reaction, bacterial contamination, sepsis, transfusion related acute lung injury, and underlying disease or drug fever. A fever of 39 degrees Celsius or more, a rise of over 2 degrees Celsius, rigors with hypotension, or any pain or dark urine should be taken as a possible haemolytic or septic reaction until excluded.

• Urticaria with systemic signs: anaphylaxis, drug reaction, and mast cell disorders.

• Dyspnoea or wheeze: transfusion associated circulatory overload, transfusion related acute lung injury, asthma and anaphylaxis.

• Hypotension: acute haemolytic reaction, sepsis, anaphylaxis, hypotensive reaction (especially in patients on ACE inhibitors) and bleeding.

Initial assessment. Full vital signs, skin, airway, chest, urine colour and bleeding, with comparison with baseline observations. Check the unit and patient identity for error.

Immediate actions in order.

1. Stop the transfusion and clamp the line.

2. Assess the patient: airway, breathing, circulation, disability and exposure, and call for help if there is more than mild skin involvement.

3. Keep intravenous access with a new giving set and 0.9% sodium chloride.

4. Recheck identity of patient and unit.

5. Inform the blood bank and the responsible clinician, and return the unit and set.

6. Do not restart without authorised clinical evaluation.

Anaphylaxis (airway, breathing or circulation involved).

• Adrenaline 500 micrograms intramuscularly (0.5 mL of 1 in 1000) into the anterolateral thigh in an adult, repeated after 5 minutes if there is no improvement. Children: 300 micrograms at 6 to 12 years and 150 micrograms at 6 months to 6 years.

• High flow oxygen, the patient lying flat with legs raised (sitting if breathless).

• 0.9% sodium chloride 500 to 1000 mL by rapid bolus in an adult (10 mL/kg in a child), repeated as needed.

• Chlorphenamine 10 mg intravenously (5 mg at 6 to 12 years, 2.5 mg at 1 to 5 years) and hydrocortisone 200 mg intravenously (100 mg at 6 to 12 years, 50 mg at 6 months to 6 years) as second line only.

• Salbutamol nebulised for bronchospasm, and an adrenaline infusion in refractory shock with intensive care.

Moderate allergic reaction. Chlorphenamine 10 mg intravenously, observe airway and breathing, and hydrocortisone if symptoms are widespread.

Mild allergic reaction (isolated urticaria or itch). Pause the transfusion, give chlorphenamine 10 mg, and observe. The transfusion may be restarted slowly only after the clinician authorises it, when all symptoms have resolved.

Febrile reaction. Paracetamol 1 g in an adult (15 mg/kg in a child), keep the patient warm if shivering, and recheck observations every 15 minutes. After serious causes are excluded, and only on the clinician's authorisation, the transfusion may continue with slower rate if the reaction is isolated and mild.

Investigations. For all but mild isolated reactions: return the unit and set, repeat group, antibody screen and direct antiglobulin test, full blood count, haemolysis markers, and blood cultures if fever is high or the patient looks unwell. After anaphylaxis, measure mast cell tryptase within 1 to 2 hours and again at 24 hours, and later test serum IgA, anti-IgA and haptoglobin.

Observation. After mild reactions, observe until resolved. After anaphylaxis, observe for at least 6 to 12 hours because of biphasic reactions, and give the patient an adrenaline auto-injector plan where relevant.

Further transfusion.

• After a febrile reaction: leucodepleted products (usually already used), and for repeated reactions consider plasma reduced or washed platelets.

• After a mild allergic reaction: pause and restart if authorised, and for repeated mild reactions consider washed products or antihistamine given with the transfusion.

• After anaphylaxis: do not transfuse again without specialist review, use washed red cells and platelets, or IgA deficient donor products for confirmed anti-IgA, and give in a monitored setting with adrenaline ready.

Premedication. Routine antihistamines, steroids and antipyretics are not reliably effective in preventing reactions and may hide early signs. They are reserved for patients with documented recurrent mild reactions.

Reporting. Report every reaction to the transfusion service and the haemovigilance system, report anaphylaxis as serious, and record severity and imputability.

Prevention. Leucodepletion, plasma reduced or washed products for recurrent reactions, awareness of IgA deficiency, avoidance of unnecessary transfusion, careful observation in the first 15 minutes and ready access to adrenaline.