Complications of Blood Transfusion: Reactions, Prevention and Emergency Care

Complications of Blood Transfusion: Acute Reactions, Delayed Effects and Emergency Management

Study level: Clinical medicine, emergency medicine and pathology | Topic: Hematology and transfusion medicine

Learning objectives

• Classify acute, delayed, immune and nonimmune transfusion complications.
• Recognise haemolytic, febrile, allergic, septic, TRALI and TACO presentations.
• Explain delayed haemolysis, alloimmunisation, iron overload and transfusion-associated GVHD.
• Apply a stepwise investigation and emergency response.
• Prevent complications through patient selection, component modification and haemovigilance.

1. Classification by timing

Timing	Examples	Clinical significance
During/within 24 hours	Acute haemolysis, febrile reaction, urticaria/anaphylaxis, bacterial sepsis, TRALI, TACO, hypotension, citrate toxicity and hypothermia.	May progress to shock, respiratory failure, DIC or cardiac arrest.
Days to weeks	Delayed haemolysis, post-transfusion purpura, alloimmunisation and some infections.	Falling Hb, jaundice, thrombocytopenia or difficulty finding compatible blood.
Months to years	Iron overload, transfusion-transmitted infection, chronic GVHD and repeated alloantibody formation.	End-organ injury and complex future transfusion support.

2. Acute immune reactions

2.1 Acute haemolytic transfusion reaction (AHTR)

Usually caused by ABO-incompatible RBCs from identification or clerical error. Recipient IgM activates complement, causing intravascular haemolysis, cytokine release, vasodilation, DIC and renal tubular injury. Other clinically significant antibodies can also cause reactions.

• Symptoms: fever, rigors, flushing, chest/back/flank pain, dyspnoea, nausea, anxiety/impending doom, hypotension, bleeding and dark urine.
• Signs/tests: haemoglobinuria, raised LDH/indirect bilirubin, low haptoglobin, positive DAT, rising creatinine, hyperkalaemia and DIC.
• Immediate care: stop transfusion, maintain IV access with compatible fluid, verify identity, notify blood bank, send blood/unit/urine samples, support shock and renal function, monitor potassium and coagulation.

2.2 Febrile non-haemolytic transfusion reaction (FNHTR)

A temperature rise of at least 1°C or fever with chills/rigors during or soon after transfusion, usually from cytokines or antibodies to donor leukocytes. It is a diagnosis of exclusion: bacterial contamination and haemolysis must be ruled out before attributing fever to FNHTR.

2.3 Allergic and anaphylactic reactions

• Mild: isolated urticaria, pruritus or flushing due to donor plasma proteins.
• Severe: bronchospasm, angioedema, hypotension or shock; IgA-deficient recipients with anti-IgA are a classic risk group.
• Management: stop and assess. Mild isolated symptoms may receive an antihistamine under policy; anaphylaxis requires immediate IM adrenaline, airway/oxygen support and fluid resuscitation.

3. Acute nonimmune reactions

Complication	Mechanism/causes	Clinical clues
TRALI	Donor antibodies/mediators activate recipient neutrophils, causing noncardiogenic pulmonary oedema.	Acute hypoxia, bilateral infiltrates and respiratory distress during or within hours, without primary circulatory overload.
TACO	Rapid or excessive volume in a patient with limited cardiac/renal reserve.	Dyspnoea, hypertension, raised JVP, pulmonary oedema, positive fluid balance and response to diuresis.
Septic transfusion reaction	Bacterial contamination, especially platelets stored at room temperature.	High fever, rigors, vomiting, hypotension, shock and DIC.
Mechanical haemolysis	Improper warming, freezing, pressure pumps, small needles or incompatible IV solutions.	Pink/red plasma, haemoglobinuria and falling Hb without expected antibody findings.
Nonimmune haemolysis	Overheating, hypotonic fluids, contaminated line or damaged unit.	Haemolysis with negative immune work-up; inspect equipment and unit.
Hypothermia	Rapid infusion of cold components.	Arrhythmia, coagulopathy, impaired oxygen unloading and worsened shock.
Citrate toxicity	Citrate chelates ionised calcium during rapid/massive transfusion.	Perioral tingling, hypotension, tetany, QT prolongation and arrhythmia.
Hyperkalaemia	Potassium leakage from stored RBCs, amplified by renal failure/rapid massive transfusion.	Weakness, ECG changes, ventricular arrhythmia or cardiac arrest.
Air embolism	Improper pressure/catheter handling, rare with standard systems.	Sudden dyspnoea, chest pain, neurologic deficit or cardiovascular collapse.

4. Delayed immune complications

4.1 Delayed haemolytic transfusion reaction

An antibody titre falls below detection after an earlier exposure, then rises days to weeks after re-exposure. Extravascular haemolysis causes an unexpected Hb fall, jaundice, fever or dark urine. Repeat antibody screen, DAT, bilirubin, LDH, haptoglobin and blood film; notify the blood bank so future units are antigen-negative.

4.2 Alloimmunisation

Recipients form antibodies to RBC, platelet or HLA antigens after transfusion or pregnancy. Alloimmunisation can cause delayed haemolysis, platelet refractoriness, haemolytic disease of the fetus/newborn and difficulty finding compatible units. Use extended phenotype/genotype matching in chronically transfused patients.

4.3 Post-transfusion purpura

Rare severe thrombocytopenia occurs about 5–10 days after exposure, often in previously sensitised individuals. It may cause mucosal, GI or intracranial bleeding; urgent haematology assessment and IVIG are typical specialist therapies.

4.4 Transfusion-associated GVHD

Viable donor T cells engraft and attack recipient skin, gut, liver and marrow, causing fever, rash, diarrhoea, hepatitis and pancytopenia days to weeks later. Mortality is high. Prevention is irradiation of cellular components for defined high-risk recipients and directed donations.

5. Transfusion-transmitted infections

Donation screening and pathogen-reduction reduce but do not eliminate risk. Possible agents include HIV, hepatitis B/C, malaria, syphilis, bacteria, parasites and emerging viruses. A recipient with unexplained fever, hepatitis, haemolysis or sepsis after transfusion requires investigation and haemovigilance reporting. Maintain traceability of donor unit and recipient samples.

6. Iron overload and chronic complications

• Repeated RBC transfusions deposit iron in liver, heart, pancreas and endocrine organs.
• Monitor cumulative exposure, ferritin and organ iron (MRI where available) in chronic transfusion disorders.
• Iron chelation is specialist-directed; adherence and renal/hepatic safety monitoring are essential.
• Chronic transfusion also increases alloimmunisation, transfusion dependence, venous access complications and infection exposure.

7. Massive-transfusion complications

Problem	Why it occurs	Monitoring/prevention
Dilutional coagulopathy	Loss/dilution of platelets and factors.	Balanced components; serial fibrinogen, PT/aPTT, platelets and viscoelastic tests.
Hypocalcaemia	Citrate binds ionised calcium.	Serial ionised calcium and protocol-guided calcium replacement.
Hyperkalaemia	Stored RBC potassium and tissue injury.	ECG/electrolytes; use appropriate products and treat hyperkalaemia.
Hypothermia	Large volumes of cold blood/fluid.	Active warming and blood warmers where approved.
Acidosis then alkalosis	Shock/lactate initially; citrate metabolism later.	Serial blood gases; treat perfusion rather than bicarbonate reflexively.
TACO	High volume/rate in limited cardiac/renal reserve.	Slow targeted transfusion, fluid balance and diuretic strategy when appropriate.
TRALI	Inflammatory lung injury from donor mediators.	Recognise early, avoid unnecessary plasma and report to blood service.

8. Universal emergency response

1. Stop the transfusion immediately. Keep the IV line open with compatible fluid through new tubing if required.
2. Assess airway, breathing, circulation, disability, exposure, temperature, glucose and urine output.
3. Recheck the patient’s identity, unit number, blood group and compatibility label at the bedside.
4. Notify the prescriber, senior clinician and blood bank; do not discard the bag or tubing.
5. Send post-reaction blood and urine samples, the component bag/tubing and cultures as directed.
6. Treat the syndrome: adrenaline for anaphylaxis, oxygen/ventilation for TRALI, cautious diuresis for TACO, antimicrobials for sepsis, shock/renal support for haemolysis and calcium/temperature control in massive transfusion.
7. Document the event and complete haemovigilance reporting; update the patient’s transfusion history and allergy/antibody record.

9. Prevention

• Use a clear indication and PBM plan; avoid unnecessary units.
• Correctly identify the patient and label specimens at bedside.
• Use ABO/Rh typing, antibody screening and cross-match; maintain historical antibody records.
• Select leukoreduced, irradiated, washed or antigen-negative products when indicated.
• Assess volume tolerance, transfuse slowly when appropriate and monitor high-risk patients.
• Educate patients to report delayed jaundice, dark urine, fever, rash, breathlessness or unusual bleeding after discharge.

10. Clinical cases

Case 1: fever and rigors

Fifteen minutes after platelet transfusion, a patient develops high fever, rigors and hypotension. Do not call this a simple febrile reaction. Stop transfusion, culture patient and component, start sepsis resuscitation and notify the blood service for possible bacterial contamination.

Case 2: pulmonary oedema

An elderly patient with renal failure becomes hypoxic and hypertensive after two units. Raised JVP and a positive fluid balance suggest TACO, but obtain imaging and assess for TRALI, pneumonia and cardiac ischemia. Stop/slow transfusion, oxygenate and treat volume overload.

Case 3: delayed haemolysis

Ten days after transfusion, Hb falls with jaundice and a positive DAT. Send antibody identification and haemolysis studies, notify the blood bank and provide antigen-negative units if further transfusion is essential.

11. Quick self-test

1. What is the first action in every suspected transfusion reaction?
2. Differentiate TRALI and TACO.
3. Which reaction can cause fever, shock and DIC from contaminated platelets?
4. Why does delayed haemolysis occur days after a seemingly compatible transfusion?
5. How is transfusion-associated GVHD prevented?
6. List four complications of massive transfusion.

Answers

1. Stop the transfusion and assess ABCDE.
2. TRALI is inflammatory noncardiogenic lung injury; TACO is hydrostatic volume overload, often with hypertension and raised filling pressures.
3. Septic transfusion reaction.
4. An anamnestic response to a previously encountered RBC antigen produces a delayed antibody rise and haemolysis.
5. Irradiate cellular blood components for defined high-risk recipients and directed donations.
6. Hypocalcaemia, hyperkalaemia, hypothermia, dilutional coagulopathy, acidosis, TACO and TRALI.

Key take-home points

• Stop first, investigate second: continuing a suspect transfusion can turn a manageable reaction into fatal shock.
• ABO haemolysis, bacterial sepsis, anaphylaxis, TRALI and TACO are immediately life-threatening.
• Delayed haemolysis, alloimmunisation, GVHD and iron overload affect future health and future compatibility.
• Correct identification, component selection, monitoring and haemovigilance prevent more harm than any single laboratory test.

Selected references

• NCBI Bookshelf: Transfusion Reactions
• NCBI Bookshelf: Hemolytic Transfusion Reaction
• MedlinePlus: Hemolytic transfusion reaction
• WHO: Clinical transfusion process and patient safety