Transfusion medicine handbook

6. Special Circumstances

6.8 Complications of Acute Blood Loss Associated with Large Volume Transfusions

When there is no pre-existing haemostatic problem, replacement of up to one blood volume (8 - 10 units of blood in an adult) using red cells and non-plasma fluids is unlikely to cause haemostatic problems due to dilution. Transfusion of much larger volumes may however lead to:

• Microvascular bleeding
  When major blood loss and massive transfusion is complicated by microvascular bleeding, with or without laboratory evidence of disseminated intravascular coagulation (DIC), the platelet count should be maintained > 50 x 10⁹/L. With severe diffuse microvascular bleeding, a target platelet count ≥ 100 x 10⁹/L is recommended (but this may be difficult to achieve and blindly giving multiple bags of platelets to try to reach a target is not appropriate).

To avoid dilutional coagulopathy use of non-blood products should be restricted until laboratory evidence that any haemostatic failure is corrected. FFP is indicated if the microvascular bleeding is accompanied by prolonged PT/APTT > 1.5 times the mean control or the fibrinogen is < 1.0 g/L (< 1.5 g/L with laboratory evidence of disseminated intravascular coagulation). With persisting severe hypofibrinogenemia despite FFP, administration of cryoprecipitate is recommended.

While there is no evidence that the prophylactic transfusion of FFP or platelets to patients receiving large volume transfusions reduces the risk of microvascular bleeding, these blood components are included empirically in massive transfusion protocols in an attempt to maintain the platelet count > 50 x 10⁹/L and PT/APTT < 1.5 times the mean control.

• Hypocalcaemia
  The citrate anticoagulant in some blood components (e.g. FFP) binds ionised calcium. It should be noted that red cells in additive solution contain only traces of citrate.
  Usually the rapid metabolism of citrate by the liver prevents lowering of plasma ionised calcium. In neonates and patients who are hypothermic, the combined effects of hypocalcaemia and hyperkalaemia may be cardiotoxic. If there is ECG or clinical evidence of hypocalcaemia, 5 mL of 10% calcium gluconate (for an adult) should be given intravenously. If necessary, the dose should be repeated until the ECG is normal.
• Hyperkalaemia
  The plasma or additive solution in a unit of red cells or whole blood stored for four to five weeks may contain 5 - 10 mmol of potassium. In the presence of acidaemia and hypothermia this additional potassium load can lead to cardiac arrest.
• Hypothermia
  The rapid transfusion of blood at 4°C can lower the body’s core temperature by several degrees. Keeping the patient warm is the best safeguard to prevent this problem. A blood warmer should be used in adults receiving large volumes of blood transfused at rates above 50 mL/kg/hour (in children above 15 mL/kg/hour).
  It should be noted that hypothermic patients with a core body temperature < 35°C may be functionally coagulopathic even though coagulation tests performed in the laboratory at 37°C may be normal.
• Acid-base disturbances
  Despite the lactic acid content in transfused blood (1 - 2 mmol/unit), fluid resuscitation usually improves acidosis in a shocked patient. In practice, transfused citrate can contribute to metabolic alkalosis when large volumes of plasma components are transfused.
• Adult respiratory distress syndrome
  The risk is minimised if tissue oxygenation is optimised by good perfusion and over transfusion is avoided. The use of albumin solutions to maintain plasma oncotic pressure is often stated to be important but controlled studies have not proven any advantage of albumin solution over crystalloid fluids for resuscitation.

It should be noted that trauma (which may be the cause of major blood loss) is also known to cause or contribute to hypothermia, acidosis and coagulopathy, and therefore may lead to the problems described in association with massive transfusion.