Massive Transfusion Syndrome

Massive transfusion syndrome is the group of metabolic, haematological and haemodynamic complications that follow replacement of the circulating blood volume, defined as 10 or more units of red cells in 24 hours, 4 or more units in 1 hour with ongoing bleeding, or replacement of over 50% of blood volume within 3 hours.

Epidemiology. Massive transfusion is needed in about 1 to 3% of civilian trauma admissions, and in obstetric, vascular and gastrointestinal haemorrhage. Mortality is 20 to 40%.

Complications. Dilutional coagulopathy and thrombocytopenia, hypofibrinogenaemia, hypothermia, acidosis, citrate toxicity with hypocalcaemia and hypomagnesaemia, hyperkalaemia (and later hypokalaemia), transfusion related acute lung injury, transfusion associated circulatory overload, haemolytic reactions, hypocalcaemia related myocardial depression and arrhythmia.

Lethal triad. Hypothermia, acidosis and coagulopathy reinforce each other.

Pathophysiology. Stored blood is cold, acidic, low in platelets, fibrinogen and factors V and VIII, high in potassium and rich in citrate. Citrate binds calcium and is normally metabolised by the liver, but shock and rapid transfusion overwhelm this.

Presentation is diffuse oozing from wounds and puncture sites, hypotension unresponsive to volume, arrhythmia, hypothermia (core temperature under 35 °C), tetany or prolonged QT, and respiratory distress.

Red flags.

• Ionised calcium under 1.0 mmol/L, or QT prolongation.
• Core temperature under 35 °C or pH under 7.2.
• Fibrinogen under 1.5 g/L, or platelets under 50 x 10^9/L.

Repeat every 30 to 60 minutes: arterial gas with lactate, potassium and ionised calcium, haemoglobin, platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, viscoelastic testing and temperature. Do ECG when calcium or potassium is abnormal.

Differential diagnosis. Disseminated intravascular coagulation, trauma induced coagulopathy, anticoagulant effect, haemolytic transfusion reaction and sepsis.

Activate the massive transfusion plan. Give red cells, plasma and platelets in a ratio near 1 to 1 to 1 (or whole blood), warmed through a fluid warmer. Avoid excess crystalloid.

Targets.

• Temperature over 36 °C, pH over 7.2, ionised calcium over 1.1 mmol/L, potassium 4.0 to 5.0 mmol/L.
• Platelets over 50 x 10^9/L (over 100 x 10^9/L in head injury or ongoing major bleeding).
• Fibrinogen over 1.5 to 2.0 g/L, prothrombin time ratio under 1.5.
• Haemoglobin 70 to 90 g/L, higher with cardiac disease or ongoing bleeding.

Calcium. Calcium chloride 10% 10 mL IV (central line) or calcium gluconate 10% 20 to 30 mL IV, after each 4 units of red cells or earlier if ionised calcium is low. Avoid mixing with blood in the same line.

Fibrinogen. Cryoprecipitate 2 pools (about 10 units) or fibrinogen concentrate 3 to 4 g IV for fibrinogen under 1.5 g/L.

Tranexamic acid. 1 g IV over 10 minutes, then 1 g over 8 hours, in trauma, obstetric and surgical bleeding.

Rewarming. Forced air warmers, warmed fluids, warm theatre and extracorporeal warming for severe hypothermia.

Acidosis. Restore perfusion. Bicarbonate 50 mmol IV for pH under 7.1.

Hyperkalaemia. Calcium, insulin 10 units IV with glucose 25 g, and salbutamol 10 to 20 mg nebulised.

Cessation. Stop the plan once bleeding is controlled and coagulation has corrected.

Monitoring. Tests every 30 to 60 minutes during bleeding, then every 4 to 6 hours. Watch for pulmonary oedema, TRALI and TACO.

Referral and escalation. Haematology and blood bank early. Surgical or interventional control of bleeding is the priority.

Special groups. In obstetric haemorrhage, aim fibrinogen over 2.0 g/L. In renal impairment and neonates, use fresh units where possible and watch potassium. In children, give 10 to 20 mL/kg boluses of blood.