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