Blood Transfusion and Transfusion Reactions

Introduction

Blood transfusion is a common, life-saving intervention, but it is also a transplant of living human tissue and carries risks that are frequently underestimated. In the UK, serious hazards are monitored by the SHOT (Serious Hazards of Transfusion) haemovigilance scheme, whose consistent finding is that the greatest risks are not exotic infections but human error and avoidable over-transfusion.¹

The two governing principles of safe transfusion practice are therefore: transfuse only when genuinely indicated, and ensure that the right blood reaches the right patient through rigorous identification at every step.

Blood components and their indications

Restrictive transfusion thresholds

Multiple trials have shown that a restrictive approach is as safe as, and often safer than, liberal transfusion - fewer transfusions mean fewer reactions, less circulatory overload and less alloimmunisation, with no loss of benefit:²

• Threshold 70 g/L, with a target of 70-90 g/L, for most stable patients without major bleeding
• Threshold 80 g/L, target 80-100 g/L, in acute coronary syndrome and patients with chronic cardiovascular disease
• Transfuse a single unit, then clinically reassess and recheck the haemoglobin before giving more - "one unit at a time" is standard practice in the non-bleeding patient
• These thresholds do not apply in active major haemorrhage, where replacement is guided by clinical status and major haemorrhage protocols rather than a haemoglobin number

Compatibility and pre-transfusion testing

The ABO system

The ABO system is uniquely dangerous because anti-A and anti-B antibodies occur naturally (they are IgM, present without prior sensitisation) and activate complement powerfully. Transfusing ABO-incompatible red cells therefore causes immediate, severe intravascular haemolysis.

The RhD system

Anti-D antibodies are not naturally occurring - they develop only after sensitisation through transfusion or pregnancy. This matters most in women of childbearing potential, in whom sensitisation risks haemolytic disease of the fetus and newborn in future pregnancies. RhD-negative females of childbearing potential should receive RhD-negative blood, and this is why O RhD-negative is the default emergency group.

Laboratory testing

• Group and save (group and screen) - determines ABO/RhD group and screens for atypical red cell antibodies; the sample is held so units can be issued quickly if needed
• Crossmatch - the patient's serum is tested against donor cells (or an electronic crossmatch is issued where the antibody screen is negative and records are established), reserving specific units
• Emergency issue - O RhD-negative units are available immediately without any testing when there is no time to wait; group-specific blood typically takes ~10-15 minutes and fully crossmatched blood ~45 minutes
• Specialised products: irradiated components for patients at risk of transfusion-associated graft-versus-host disease (e.g. after certain chemotherapies, stem cell transplant, Hodgkin lymphoma); CMV-negative components for intrauterine transfusion, neonates and in pregnancy. All UK components are leucodepleted as standard, which has substantially reduced febrile reactions and CMV transmission

Safe administration

• Valid consent - discuss the indication, risks, benefits and alternatives, and document the discussion. Patients should be given written information where possible, and told they have been transfused
• Positive patient identification at sampling - ask the patient to state their full name and date of birth, check against the wristband, and label the sample tube at the bedside, never in advance and never away from the patient
• Bedside checking before administration - two-person or electronic check confirming patient identity against the unit's compatibility label, component type, group, expiry and any special requirements
• Baseline observations before starting, repeat observations 15 minutes into each unit, and at completion; monitor closely throughout
• Visual inspection of the unit for discolouration, clots or damage to the pack
• Complete each red cell unit within 4 hours of removal from controlled storage
• Prescribe explicitly, including component, number of units, rate and any special requirements, and document the indication

Acute transfusion reactions

The immediate management of almost any acute reaction begins the same way: stop or pause the transfusion, keep IV access open with saline, assess the patient using ABCDE, and recheck the patient's identity against the unit. What follows depends on the type of reaction.

Delayed complications

• Delayed haemolytic transfusion reaction - occurring days to weeks later from an anamnestic response to a previously sensitising red cell antigen; presents with falling haemoglobin, jaundice and a positive direct antiglobulin test
• Alloimmunisation - development of antibodies to red cell, HLA or platelet antigens, complicating future crossmatching and causing platelet refractoriness
• Transfusion-associated graft-versus-host disease (TA-GvHD) - rare but almost always fatal; donor lymphocytes attack recipient tissues. Prevented by irradiating components for at-risk patients
• Post-transfusion purpura - severe thrombocytopenia about 5-12 days after transfusion, from platelet-specific alloantibodies
• Iron overload - in chronically transfused patients (thalassaemia, sickle cell disease, myelodysplasia), requiring chelation
• Transfusion-transmitted infection - now very rare in the UK given rigorous donor selection and testing, but historically devastating, as in the infected blood scandal affecting people with haemophilia

Special situations

• Major haemorrhage - activate the local major haemorrhage protocol, giving red cells, FFP and platelets in defined ratios rather than waiting for laboratory results; use O RhD-negative until group-specific blood is available; give tranexamic acid early in trauma; correct hypothermia, acidosis and hypocalcaemia (the citrate anticoagulant in blood chelates calcium)
• Jehovah's Witnesses - many decline red cells, platelets, plasma and whole blood but may accept certain fractions, cell salvage or recombinant products. Establish and document the patient's specific wishes in advance where possible; an advance decision refusing transfusion must be respected in a competent adult. A competent adult's refusal is legally binding even if death results; the position differs for children, where a court order may be sought in an emergency
• Pregnancy and RhD - avoid sensitisation, give anti-D prophylaxis as indicated, and use RhD-negative and CMV-negative components appropriately
• Chronic transfusion dependence - monitor for and chelate iron overload, and use extended phenotype-matched blood in conditions like sickle cell disease to limit alloimmunisation

Red flags

Haemovigilance and outcomes

Transfusion in the UK is very safe by historical standards: leucodepletion of all components, stringent donor selection and testing, and electronic identification systems have made transfusion-transmitted infection extremely rare. The dominant residual risks are now human factors and over-transfusion rather than infectious ones.¹

All serious adverse events and reactions must be reported to the SHOT haemovigilance scheme and, where applicable, under the Blood Safety and Quality Regulations. SHOT's annual reports consistently identify transfusion-associated circulatory overload as a leading cause of transfusion-related death and errors in patient identification as the leading cause of wrong-component transfusion - both of which are addressed not by new technology but by careful, unhurried adherence to the checking process and by transfusing restrictively, one unit at a time.