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PA21.1-6 | Blood Components & Clinical Uses — Part 3

Massive Transfusion: Definition and Metabolic Complications

Infographic explaining massive transfusion definition, 1:1:1 component therapy, and metabolic complications including hypocalcaemia, hyperkalaemia, and hypothermia. — **Panel A:** Massive transfusion definition, PRBC:FFP:Platelets 1:1:1 ratio, trauma patient, major trauma, obstetric haemorrhage, ruptured aortic aneurysm. **Panel B:** Citrate toxicity, citrate chelation of ionised calcium, hypocalcaemia, paraesthesias, tetany, prolonged QTc, myocardial depression. **Panel C:** Hyperkalaemia, potassium leak from stored red cells, old blood unit, acidosis or haemolysis worsening effect, peaked T waves, arrhythmias. **Panel D:** Hypothermia, cold 4°C blood, falling core temperature, impaired coagulation cascade, dilutional coagulopathy, cardiac arrhythmias.

Massive transfusion is conventionally defined as transfusion of ≥10 units of PRBC in 24 hours (or replacement of the entire blood volume in 24 hours). It is encountered in major trauma, obstetric haemorrhage, and ruptured aortic aneurysm.

Modern practice uses a 1:1:1 ratio of PRBC : FFP : Platelets to approximate whole-blood composition and prevent dilutional coagulopathy.

Metabolic complications of massive transfusion:

Complication	Mechanism	Manifestation
Citrate toxicity / Hypocalcaemia	Citrate (anticoagulant in blood bags) chelates ionised calcium; normally metabolised by liver, but overwhelmed in massive transfusion or liver failure	Paraesthesias, tetany, prolonged QTc, myocardial depression
Hyperkalaemia	Progressive potassium leak from stored red cells (especially old units); worsened by acidosis and haemolysis	Cardiac arrhythmias, peaked T waves
Hypothermia	Large volumes of cold (4°C) blood lower core temperature	Exacerbates coagulopathy, cardiac arrhythmias
Dilutional coagulopathy	Replacement of blood volume with PRBC (which lacks coagulation factors and platelets)	Prolonged PT/APTT, oozing from IV sites
Metabolic acidosis	Lactic acid from ischaemia + citric acid from blood bags	Low pH, high anion gap

Prevention: Use blood warmers, calcium gluconate supplementation, 1:1:1 transfusion ratio, and rapid damage-control surgery.

Circular wheel diagram showing five metabolic complications of massive transfusion with their mechanisms and clinical signs. — **Central Hub:** Title and overview of massive transfusion complications. **Segment 1:** Citrate toxicity mechanism, calcium binding, and hypocalcemic clinical signs. **Segment 2:** Hyperkalemia from stored RBC potassium release and cardiac manifestations. **Segment 3:** Hypothermia from cold blood storage and physiological responses. **Segment 4:** Dilutional coagulopathy mechanism and bleeding manifestations. **Segment 5:** Metabolic acidosis from lactate accumulation and respiratory compensation.

Leukoreduction and Irradiation

A four-panel medical education diagram compares leukoreduction, which removes donor white cells, with irradiation, which inactivates donor T lymphocytes to prevent specific transfusion complications. — **Panel A:** Leukoreduction filter, PRBC / platelets, trapped donor WBCs, residual WBC <5 × 10⁶/unit, reduced FNHTR, HLA alloimmunisation, CMV transmission, and platelet refractoriness.. **Panel B:** Irradiated blood component bag, gamma or X-ray irradiation 25–50 Gy, donor T lymphocytes inactivated, prevention of transfusion-associated graft-versus-host disease.. **Panel C:** Key distinction between WBC removal by leukoreduction and T-cell inactivation by irradiation, including caution that irradiation does not substitute for leukoreduction.. **Panel D:** Clinical vignette of fever, chills, and headache during transfusion without haemoglobin drop or hypotension, indicating febrile non-haemolytic transfusion reaction prevented by leukoreduced components..

Two important component modifications reduce specific risks:

Leukoreduction (white cell filtration): White cells are removed from PRBC or platelets using high-efficiency filters (reduces WBC to <5 × 10⁶/unit). Benefits:
• Prevents febrile non-haemolytic transfusion reactions (FNHTR — the commonest transfusion reaction, caused by cytokines from donor WBC)
• Prevents HLA alloimmunisation (important in patients requiring chronic platelet support)
• Reduces transmission of CMV (WBC-associated virus) — leukodepleted blood is an acceptable alternative to CMV-seronegative blood
• Reduces platelet refractoriness

Universal leukoreduction is now standard policy in many countries (UK, Canada, Australia).

Irradiation (gamma or X-ray, 25–50 Gy): Inactivates donor T-lymphocytes, preventing them from engrafting and attacking the recipient.
• Prevents transfusion-associated graft-versus-host disease (TA-GvHD) — rare but nearly universally fatal
• Indications: immunocompromised patients (haematological malignancies post-transplant, congenital immunodeficiency, intrauterine transfusion), transfusion from first-degree relatives, HLA-matched components
• Irradiation does NOT substitute for leukoreduction (T cells are inactivated, not removed).

SELF-CHECK

A patient receiving blood transfusion develops fever (38.8°C), chills, and headache 90 minutes into the transfusion, with NO haemoglobin drop and NO hypotension. Which complication is most likely, and which component modification could have PREVENTED it?

A. Acute haemolytic reaction; irradiation of the blood unit.

B. Febrile non-haemolytic transfusion reaction (FNHTR); leukoreduction.

C. Transfusion-associated graft-versus-host disease; leukoreduction.

D. Bacterial contamination; irradiation of the blood unit.

Reveal Answer

Answer: B. Febrile non-haemolytic transfusion reaction (FNHTR); leukoreduction.

FNHTR is the most common transfusion reaction — caused by cytokines released from donor leukocytes during storage (or recipient antibodies against donor HLA antigens). It presents with fever and chills WITHOUT haemolysis or haemodynamic instability. Leukoreduction (removal of WBCs) is the preventive measure. Irradiation inactivates T-lymphocytes to prevent TA-GvHD, not FNHTR. Acute haemolytic reactions present with haemoglobinuria, hypotension, and flank pain.

CLINICAL PEARL

Storage lesion mnemonic — '2-6-42 / room-5 / freeze-12': PRBCs live at 2–6°C for 42 days. Platelets live at room temperature (20–24°C) for 5 days. FFP and cryoprecipitate are frozen and last 12 months. If you remember only three numbers — 42, 5, 12 — you can reconstruct the storage table under exam pressure.