Definition

Major haemorrhage is variously defined as:

• Loss of more than one blood volume within 24 hours (around 70 mL/kg, >5 litres in a 70 kg adult)
• 50% of total blood volume lost in less than 3 hours
• Bleeding in excess of 150 mL/minute

A pragmatic clinically based definition is bleeding which leads to a systolic blood pressure of less than 90 mm Hg or a heart rate of more than 110 beats per minute.

Major haemorrhage protocols

Early recognition and intervention is essential for survival. The immediate priorities are to control bleeding (surgery and interventional radiology) and maintain vital organ perfusion by transfusing blood and other fluids through a wide-bore intravenous catheter. Successful management of major haemorrhage requires a protocol-driven multidisciplinary team approach with involvement of medical, anaesthetic and surgical staff of sufficient seniority and experience, underpinned by clear lines of communication between clinicians and the transfusion laboratory.

Major haemorrhage protocols should identify the key roles of team leader (often the most senior doctor directing resuscitation of the patient) and coordinator responsible for communicating with laboratories and other support services to prevent time-wasting and often confusing duplicate calls. In an emergency situation it is essential to ensure correct transfusion identification procedures for patients, samples and blood components are performed and an accurate record is kept of all blood components transfused. Training of clinical and laboratory staff and regular ‘fire drills’ to test the protocol and ensure the rapid delivery of all blood components are essential.

Algorithm for the management of major haemorrhage:

• Recognise blood loss and trigger major blood loss protocol
• Take baseline blood samples before transfusion for:
  • Full blood count, group and save, clotting screen including Clauss fibrinogen or
  • Near patient haemostatic testing if available
• If traumatic bleeding, and <3h from injury, give tranexamic acid 1 g bolus over 10 minutes, followed by IV infusion of 1 g over 8h (consider tranexamic acid 1 g bolus in non-traumatic bleeding, but not recommended for patients with acute gastrointestinal bleeding)
• Team leader to coordinate management and nominate team member to liaise with transfusion laboratory:
  • State patient unique identifier and location when requesting components
  • Until patient group known, use O neg in females, and consider O pos in males (to limit use of group O neg)
  • Use group-specific blood as soon as possible
  • Request agreed ratio of blood components (e.g. 6 units RBC and 4 units FFP)
  • Sent porter to lab to collect blood components urgently
• If bleeding is ongoing:
  • Until lab results are available:
    • Give further FFP 1L (4 units) per 6 units RBC
    • Consider cryoprecipitate (2 pools)
    • Consider platelets (1 adult dose, ATD)
  • If lab results are available:
    • If falling Hb - give RBC
    • If aPTT and/or PT ratio > 1.5 (compared to ‘normal pooled plasma’) - give FFP (15-20 ml/kg)
    • If fibrinogen < 1.5 g/L - give cryoprecipitate (2 pools)
    • If platelets < 50 x 10⁹/L - give platelets (1 ATD); request when platelets are < 75 x 10⁹/L
  • Continue cycle of clinical and laboratory monitoring and administration of 'goal-directed' blood component therapy until bleeding stops; N.B. use a blood warmer as soon as possible to avoid hypothermia – which exacerbates coagulopathy
    • Serial haemostatic tests should be checked regularly, every 30–60 min depending on the severity of the haemorrhage, to guide and ensure the appropriate use of haemostatic blood components
    • Repeat near patient testing every 10-15 minutes according to clinical situation and
      consciously review Ca2+ (to maintain normocalcaemia), Hb (to avoid over-transfusion), K+
      (to treat hyperkalaemia) and lactate (to guide resuscitation)
    • Consider blood cell salvage early - contact on-call anaesthetist/surgeon - to minimise
      allogeneic (donor) transfusion

Transfusion products in major haemorrhage

• Red cells
  • Red cell transfusion is usually necessary if 30–40% blood volume is lost, and rapid loss of >40% is immediately life threatening. Peripheral blood haematocrit and Hb concentration may be misleading early after major acute blood loss and the initial diagnosis of major haemorrhage requiring transfusion should be based on clinical criteria and observations.
  • For immediate transfusion, group O red cells should be issued after samples are taken for blood grouping and crossmatching. Females less than 50 years of age should receive RhD negative red cells to avoid sensitisation. The use of Kell negative red cells is also desirable in this group. Group O red cells must continue to be issued if patient or sample identification is incomplete or until the ABO group is confirmed on a second sample according to local policy.
  • ABO-group-specific red cells can usually be issued within 10 minutes of a sample arriving in the laboratory. Fully crossmatched blood is available in 30 to 40 minutes after a sample is received in the laboratory. Once the volume of blood transfused in any 24 hour period is equivalent to the patient’s own blood volume (8–10 units for adults and 80–100 mL/kg in children), ABO and D compatible blood can be issued without the need for a serological crossmatch.
  • The use of intraoperative cell salvage devices reduces the need for donor red cells in appropriate cases. When bleeding is controlled and the patient enters the critical care unit, a restrictive red cell transfusion policy is probably appropriate.
  • A standard threshold and target Hb range for red cell transfusion to provide critical life-saving support in major bleeding alongside clinical judgement on the severity of bleeding is recommended (threshold Hb 70 g/L, target range for the post-transfusion Hb level of 70–90 g/L).
• Coagulation
  • The transfusion of large volumes of red cells and other intravenous fluids that contain no coagulation factors or platelets causes dilutional coagulopathy. Major traumatic haemorrhage is often associated with activation of the coagulation and fibrinolytic systems (‘acute traumatic coagulopathy’). Plasma fibrinogen predictably falls to sub-haemostatic levels (<1.5 g/L) after 1 to 1.5 blood volume replacement (earlier in the presence of coagulopathy and hyperfibrinolysis). Coagulation is also impaired by hypothermia, acidosis and reduced ionised calcium (Ca2+) concentration. Ionised hypocalcaemia may be caused by rapid transfusion of blood components containing citrate anticoagulant, although this is uncommon in the presence of normal liver function.
  • Traditional ‘massive transfusion’ guidelines use laboratory tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) to guide blood component replacement. The usefulness of these tests is reduced by the significant delay between sampling and returning results to the clinical team. If a PT can be made available with a rapid turnaround time that allows it to reflect the clinical situation it can be used to aid decisions regarding FFP infusion. The Clauss fibrinogen assay should be used in preference to a fibrinogen estimated from the optical change in the PT (PT-derived fibrinogen) that can be misleading in this setting.
  • FFP should be transfused in doses of 12–15 mL/kg (at least four units in the average adult) to maintain the PT ratio (compared to ‘normal pooled plasma’) less than 1.5. The early transfusion of FFP in a fixed ratio to red cells (‘shock packs’) in traumatic haemorrhage, to reverse coagulopathy and reduce bleeding, has been extrapolated from military to civilian practice but the true value of this approach is uncertain. Large-volume FFP transfusion carries increased risks of circulatory overload (TACO), allergic reactions and transfusion-related acute lung injury (TRALI), and further clinical research is required to clarify its role.
  • Fibrinogen levels should be maintained above 1.5 g/L. FFP contains insufficient fibrinogen to achieve the rapid rise in levels required to support haemostasis, and supplementation in the form of cryoprecipitate or fibrinogen concentrate should be offered.
  • Once haemostasis is secured, prophylactic anticoagulation with low molecular weight heparin should be considered because of the risk of thromboembolic complications.
• Platelets
  • The platelet count usually remains above 50×10⁹/L (the generally accepted haemostatic level) until 1.5 to 2.5 blood volumes have been replaced. Many hospitals do not store platelets on site and the time for transfer from the blood centre must be factored into local protocols. Therefore, an adult therapeutic dose should be requested when the count falls to 75×10⁹/L.
• Tranexamic acid
  • The CRASH-2 trial published in 2010 clearly showed that early administration of the antifibrinolytic drug tranexamic acid improves the survival of patients with major traumatic haemorrhage or at risk of significant bleeding after trauma . Tranexamic acid should be given as soon as possible after the injury in a dose of 1 g over 10 minutes followed by a maintenance infusion of 1 g over 8 hours. Evidence is emerging of the value of tranexamic acid in other forms of major haemorrhage, including obstetric and surgical haemorrhage. Given its good safety profile, ease of administration and low cost, tranexamic acid should be considered as a component of most major haemorrhage protocols.