Management of Major Haemorrhage

(See site specific information below)

This is an abbreviated version of the full guideline on NHSAAA AthenA / Guidelines - Prescribing / Major Haemorrhage Protocol (link only active if accessing via NHS network).

Also, refer to the quick reference guide for the Management of ADULT Major Haemorrhage.

Introduction

The therapeutic goal in the management of massive haemorrhage is maintenance of tissue perfusion and oxygenation by restoration of blood volume and haemoglobin (see site specific information below).

Definition of major haemorrhage

Definition of acute massive haemorrhage varies. In adult patients (excluding obstetric patients), it can be defined as:

• blood loss >150ml/minute;
• 50% blood volume loss in <3 hours;
• loss of ≥ one blood volume within 24 hours;
• 4 unit red cell transfusion in < 4 hours with ongoing major blood loss;
• 10 unit red cell transfusion within 24 hours;
• Clinical shock.

The normal human blood volume in an adult is 65-70ml/kg; therefore a 70kg male has a blood volume of approximately 5000ml - a 50% loss is approximately 2500ml.

Bleeding in critical sites including intra-cranial, intra-spinal, intra-ocular, retroperitoneal, intra-articular, pericardial or intra-muscular with compartment syndrome should also be considered to constitute a major haemorrhage.

1. Assess: Is this major haemorrhage? (See definition above)

2. Restore circulating volume

• Wide bore peripheral cannulae
• Controlled hypotension may be tolerated while awaiting the arrival of CRC for administration. However, where necessary, adequate volumes of crystalloid or colloid, warmed if possible should be given.
• Give oxygen and start monitoring
• Aim for BP at appropriate level

3. Summon Help (See site specific information below). Seek senior staff assistance:

• Surgical?
• Anaesthetics?
• ITU?
• Emergency medicine?

4. Stop bleeding

Consider early surgical or interventional radiology involvement.

5. Send blood samples

• Emergency crossmatch: 4-6 units of red cells (RBC) will be made available – request as appropriate.
• FBC and coagulation screen including fibrinogen. 
• Biochemistry including calcium and lactate.
• Consider blood gases including lactate (arterial).
• Ensure correct labelling of samples.
• NHSAAA operates a second confirmatory sample policy before group-specific or cross-matched blood will be issued; consideration should be given to obtaining a second sample. Group O blood will be issued unless there is a second sample available to confirm blood group. Group O RhD negative red cells will always be issued for females <50 years. O negative or O positive may be issued for male patients and females over the age of 50 years.

6. Give blood products as appropriate (see below)

Blood products

Availability

• 4-6 units of RBC will be made available. Request as appropriate.  
• Where the patient being transfused has special requirements, it may be necessary to discuss with the Blood Transfusion lab +/- a haematologist if there are problems fulfilling these requirements in order for the best available blood to be issued. There should be no delay in transfusion while waiting for appropriate blood.
• Fresh frozen plasma (FFP) will be thawed for use on request. Up to 4 units of FFP can be defrosted by the lab without the need to discuss with a consultant haematologist.
• If platelets are specifically required, it is necessary to request them. 

Resuscitation

• In the first instance give FFP and RBCs in at least a 1:2 ratio unless major trauma or potential for coagulopathy in which case FFP and RBCs should be given in a 1:1 ratio and a dose of platelets considered.
• Once laboratory results become available, these should be used to guide resuscitation components as below.

Severe cases with evidence of coagulopathy, major haemorrhage or sepsis, should be discussed early with consultant haematologist regarding ongoing blood components.

Patients on anti-thrombotic therapy

For patients on combination anti-platelet agents (i.e. aspirin and clopidogrel or ticagrelor or prasugrel) with life threatening bleeding, consider a platelet transfusion in discussion with the on-call haematologist.

For patients on direct oral anticoagulants (DOACs - apixaban, dabigatran, edoxaban, or rivaroxaban) discuss with the on-call haematologist regarding the use of specific reversal agents.

For patients on warfarin (including those with prosthetic heart valves) with life threatening haemorrhage or trauma:

• Stop warfarin
• Give phytomenadione (vitamin K₁) IV 5mg (in 100ml glucose 5% over 15 – 30 minutes)
• Give intravenous prothrombin complex concentrate (Beriplex^®).
  • Dose according to table below.
  • Reconstitute 500unit vial of Beriplex^® to 20ml using the sterile water and the reconstitution device supplied.
  • Infuse immediately at an infusion rate not exceeding 8ml/minute.
  • Contraindicated in patients with allergy to heparin, citrate or with suspected heparin-induced thrombocytopenia, and use with extreme caution in patients with disseminated intravascular coagulation (DIC) or recent (<1 month) venous thromboembolism, myocardial infarction or thrombotic stroke.
  • Beriplex^® supply available from blood transfusion lab at Crosshouse or Ayr (or if out of hours, from the emergency drug cupboard).
• Recheck coagulation status after 20 – 30 minutes and at 6 hours and 24 hours (or earlier if clinically indicated). Further doses of phytomenadione (Vitamin K₁) may be required in extreme circumstances.

Beriplex^® dose adjustment according to INR

For intravenous unfractionated heparin (UFH), reversal is rarely required due to the very short half-life. Similarly, the reversal of low molecular weight heparins (LMWH) is rarely required >12 hours after administration provided normal renal function. If however reversal is still thought to be necessary, protamine will neutralise the effects of heparins to varying amounts. N.B. A coagulation sample can be taken requesting an UFH or LMWH anti-Xa level. These are analysed locally via arrangement with the laboratory.

• Care must be taken during the administration and calculation of protamine doses.
• The dose of protamine is dependent on the amount and type of heparin to be neutralized, its route of administration and the time elapsed since it was last given, since heparin is continuously being excreted.
• Ideally, the dose required to neutralize the action of heparin should be guided by blood coagulation studies.
• Administer protamine up to a maximum of 50mg in a single dose as slow IV infusion over 10 minutes (for dosing information, see protamine's Summary of Product Characteristics).
• Anaphylaxis has been reported, see the Anaphylaxis guideline for management.
• Avoid protamine in patients with allergies to fish or fish products.

Fondaparinux (Arixtra^®) is an injectable indirect factor Xa inhibitor with no known antidote. Refer to fondaparinux's Summary of Product Characteristics for further information. 

In Massive Transfusion remember:

Allow at least:

• 25 minutes for thawing of plasma products
• 15 minutes for group specific red cells
• Up to 45 minutes for full crossmatch unless antibodies are present in which case least incompatible will be issued 
• Transport time

Other Information

• If emergency O negative used please inform Blood transfusion lab as soon as possible to ensure replacement of units.
• Avoid wastage of blood products - return blood immediately to the Blood Transfusion lab or satellite fridge if not being used.
• Packed red cells should not be lying out of fridge for more than 30 minutes. If a unit of blood will not be used in that time, it should be returned to the blood fridge, if however this has not occurred the unit can be transfused up to 4 hours from removal from fridge to minimise wastage.   
• Once situation resolved, inform lab staff and porters to allow them to stand down.
• Once cycle completed review clinical situation.
• Tranexamic acid (off-label use) should be considered in bleeding trauma or surgical patients (most effective if given early, i.e. <3 hours from trauma). Dose is tranexamic acid IV 1g over 10 minutes, then infusion of 1g over 8 hours. The recent HALT-IT study has shown that there is no benefit in the use of tranexamic acid in gastrointestinal bleeding; hence, should not be used in gastrointestinal bleeding outside the context of a clinical trial.

Hospital Specific Information on Massive Haemorrhage Management