Major Haemorrhage (bsh 2022, bsh 2015)


Definitions


Massive blood loss definitions:

  • Loss of one blood volume in 24 hours

  • 50% blood volume loss in 3 hours

  • Blood loss of 150ml/min

 

Major Haemorrhage definition:

  • Bleeding that results in HR >110 and/or Sys BP <90

 

Organisational Principles

 

Hospitals must have a major haemorrhage protocol

Hospital Transfusion Committee (HTC) oversee protocol development and implementation

Hospital Transfusion Team (HTT) support all activities essential for effective use of the protocol


Major haemorrhage protocols should include:

  • A site-specific protocol for the processes, people and blood components required to treat bleeding patients

  • The details required to activate the transfusion emergency

  • Structured communication between teams with easily identifiable terminology

  • The process for de-activating the protocol (to minimise wastage)

  • Audit, SHOT reporting, Staffing levels, Training & Competency, De-briefing are all essential to successful implementation and management of the protocol.


MDT required for major haemorrhage

  • Switchboard

  • Porters

  • Transfusion Lab Staff

  • Senior nurse / midwife / clinician

  • Stop the bleeding – radiology, surgery, obstetrics, endoscopy

  • Haematologist

 

Transfusion Support

 

Principles

  • Supports the primary aim of local control of bleeding

  • Accurate documentation required to fulfil legal obligation for traceability

  • Blood warmers and pressure infusers should be available in relevant clinical areas

  • If <3 hours since traumatic injury, give TXA 1g IV bolus, followed by 8 hour infusion

 

Upfront Order

  • Red Cells 4-6 units

  • FFP 15-20ml/kg

  • Platelets 1 unit

  • Cryoprecipitate 2 units

 

Coag Tests

  • Aim to perform every 30-60 minutes during major haemorrhage

  • PT possibly more sensitive than APTT to coagulation factor deficiency in trauma

  • Clauss fibrinogen should be used (but false high levels with use of colloid fluids)

  • Turnaround times seem an important barrier to correction of coagulopathy, despite this —>

  • Point-of-care ROTEM / TEG not shown to improve mortality / morbidity vs laboratory testing

  • See below for ROTEM / TEG transfusion threshold

 

Tranexamic Acid

  • No increased risk of thrombosis (JAMA 2021 meta-analysis)

  • Reduces mortality in trauma and post-partum haemorrhage

  • This benefit persists if administered up until 3 hours after onset of bleeding


Red Cells

  • Purpose: Oxygen-carrying capacity + prompt axial flow and margination of plasma/platelets

  • General Target: Hb 70-900g/l

  • Red cell Tx usually becomes necessary after loss of 30-40% of blood vol (1500ml for 70kg)

  • Blood warmers should be used to prevent hypothermia

  • Does age of red cells matter? ABLE 2015 and RECESS 2015 trials say no

  • Consider remote blood fridges in large institutions

  • Consider cell salvage

 

Fresh Frozen Plasma

  • Purpose: Provide coagulation factors and support volume expansion

  • Dose: 15-20ml/kg

  • Aim for FFP:RBC ratio between 1:1 – 1:2 until bleeding controlled (avoid ratios >1:2)

  • General Target: PT/APTT < 1.5x ULN

  • PROPPR 2015 study – no difference 1:1:1 vs 1:1:2 of FFP:PLT:RBC

 

Cryoprecipitate (And/Or FGN concentrates)

  • Purpose: Replace Fibrinogen

  • 1 adult unit = 5 donations pooled to produce a single bag

  • Dose: 2 adult units (Approx. 1g/l increase in FGN)

  • Alternative: Fibrinogen concentrate products - dose 4-5g —> approx. 1g/l increase in FGN

  • FGN level <1 is likely after 1-1.5 times blood volume replacement

  • General Target: Maintain FGN >1.5g/l

 

Platelets

  • Thrombocytopenia typically occurs after 1.5 times blood volume replacement

  • 1 pooled unit = 4 donations pooled to produce a single bag

  • 1 apheresis unit = 1 donations via apheresis to produce a single bag

  • Dose: 1 adult unit (pooled or apheresis)

  • General Target: Maintain platelet count >50


Other Products

  • Prothrombin Complex Concentrate - no specific role in major haemorrhage not involving anticoagulants

  • Aprotinin - bovine serine protease inhibitor - has a specific role in cardiopulmonary bypass

  • Desmopressin - no specific role

  • Recombinant activated Factor VII (NovoSeven) - high risk arterial thrombosis


Cell Salvage

  • Rapid re-supply of RBC, 250ml approx = to 1 unit allogeneic red cells

  • Not cost-effective for most centres

 

Specific Scenarios

 

Obstetric haemorrhage

  • PPH = >500ml vaginal birth or >1000ml caesarean section

  • Still a leading cause of obstetric death

  • Tranexamic Acid

    • WOMAN 2017 - >20,000 patients. TXA for post-partum haemorrhage. 19% reduction in death, benefit time-dependent (best given within 3 hours of onset of bleeding).

    • No benefit to prophylactic use of TXA prior to vaginal delivery (NEJM 2018)

  • Maintain FGN >2.0

    • FGN increase during pregnancy so ‘normal’ range at delivery 4-6g/l (vs 2-4g/l non-pregnant)

    • Increasing use of FGN concentrate instead of cryoprecipitate. No consensus. ?Concentrate perceived to be quicker as no thawing time. ?Cryo a broader product as not just FGN. Trials to date do not appear to support early administration of FGN concentrate (FIB-PPH 2015, OBS-2 2017, FIDEL 2021)

 

GI Bleeding

  • Restrictive strategy (Hb 70g/l) associated with improved outcomes

  • Additional risk associated with elevating portal pressures via transfusion in liver patients

  • TXA not recommended for GI bleeding

  • HALT-IT 2020 - No benefit from high dose TXA in acute GI bleeding. Increased rate of thrombosis. Contrasts with trials of TXA in other major haemorrhage settings, why? CRASH-2 and WOMAN showed importance of giving TXA within 3 hours of bleeding onset to achieve survival benefit - often hard to time the onset of GI bleeding, likely receiving medical attention hours after bleeding starts.

 

Trauma

  • Acute Traumatic Coagulopathy / Trauma Induced Coagulopathy (TIC) - Poorly defined but distinct syndrome seen in 25% of major trauma cases at presentation. TIC is a primary endogenous event, closely followed by secondary events (e.g. dilutional and consumptive processes).

  • Trials of roadside blood products (RBCs, FFP etc) inconclusive to date

  • CRASH-2 Study lead to widespread uptake of TXA in major haemorrhage

    • >20,000 patients. Death within 4 weeks of traumatic injury was reduced by 9% vs placebo

    • TXA now administered at the roadside

  • Trials of interest:

    • PROMMTT 2013 - Oberservational study. 30% of patients that died from haemorrhage did so before receiving platelets. Established the trial design for PROPPR.

    • PROPPR 2015 – Underpowered but no difference in primary outcomes for 1:1:1 vs 1:1:2 of FFP:PLT:RBC. Secondary outcomes showed death from haemorrhage lower in 1:1:1 group (assessed unblinded).

    • PAMPER 2018 - 500 pre-hospital patients, pre-thawed plasma versus standard of care. Lower 30-day mortality in plasma group. (COMBAT 2018 similar, smaller no. of patients, found no difference in outcomes)

    • CRASH-3 2019 - >12,000 patients. TXA within 3 hours of acute traumatic brain injury. Primary outcome was head injury related death within 28 days. Benefit seen for mild injury (GCS 9-15 and pupils reactive)

    • iTACTIC 2021 - 400 patients. Viscoelastic assays versus conventional coag tests to guide management of major trauma haemorrhage. No difference in No. patients alive at 24 hours / free of massive haemorrhage at 24 hrs / alive at 28 days

    • RePHILL 2022 - 400 pre-hospital patients. RBC + lyophilised plasma vs Normal Saline. Recruitment terminated early due to pandemic. No difference in composite primary outcome.

    • CRYOSTAT-2 2023 - 1600 patients. Addition of 3 units cryo on arrival to hospital versus standard care. No difference in 28-day all cause mortality.

 

Surgery

  • BSH 2022 recommend 1g TXA prior to skin incision for all inpatient surgery

  • POISE-3 2022 - 9500 patients. Prophylactic TXA vs placebo prior to non-cardiac surgery. Reduced composite bleeding outcome with TXA. Small difference in composite CVS outcome. Authors conclude noninferiority of TXA not established.


Paediatrics

  • Not little adults

  • Principles the same but anatomy & physiology differ, not just size and height

 

Viscoelastic Assay interpretation in major haemorrhage

From BSH guideline, itself based on iTACTIC trial design


Example of a Major Blood Loss Protocol

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