Major Haemorrhage in Adults

Topic Overview

Summary

Major haemorrhage is life-threatening acute blood loss requiring immediate massive transfusion and source control. It is defined by transfusion of ≥4 units of packed red blood cells (pRBC) in less than 1 hour, ≥10 units in 24 hours, or blood loss causing haemodynamic instability. Causes include trauma (30-40% of trauma deaths), gastrointestinal bleeding, postpartum haemorrhage, surgical complications, and ruptured aneurysms. Early activation of the major haemorrhage protocol (MHP) with balanced resuscitation (1:1:1 ratio of pRBC:FFP:platelets), tranexamic acid within 3 hours, permissive hypotension in trauma (SBP 80-90 mmHg), and aggressive prevention of the lethal triad (hypothermia, acidosis, coagulopathy) are essential to survival. Damage control resuscitation prioritises haemostatic resuscitation over crystalloid-based approaches.

Key Facts

• Definition: Blood loss requiring ≥4 units RBC in less than 1 hour OR ≥10 units in 24 hours OR causing haemodynamic instability [1]
• Shock index: Heart rate ÷ systolic BP; > 1.0 indicates significant haemorrhage (normal 0.5-0.7) [2]
• Balanced resuscitation: pRBC:FFP:platelets = 1:1:1 reduces mortality from exsanguination [3]
• Tranexamic acid: 1g IV within 3 hours reduces mortality by 1.5% (NNT ~67); harmful if given > 3 hours [4,5]
• Permissive hypotension: Target SBP 80-90 mmHg in non-head-injured trauma until haemorrhage control [6]
• Lethal triad: Hypothermia (less than 35°C) + acidosis (pH less than 7.2) + coagulopathy = exponential mortality increase [7]
• Trauma-induced coagulopathy: Present in 25-35% of major trauma patients on arrival; independently predicts mortality [8]
• Fibrinogen critical threshold: less than 1.5 g/L requires immediate replacement with cryoprecipitate or fibrinogen concentrate [9]
• Calcium replacement: Ionised calcium less than 1.0 mmol/L impairs coagulation; replace during massive transfusion [10]

Clinical Pearls

Shock index > 1.0 = assume major haemorrhage — Even if blood pressure appears "normal", HR/SBP > 1 indicates ≥30% blood volume loss [2]

TXA time-critical — Benefit only within 3 hours of injury onset. Every 15-minute delay reduces efficacy. No benefit and potential harm after 3 hours [4,5]

"Damage control" not "damage limitation" — Active intervention to prevent the lethal triad, not passive acceptance. Warm the patient, transfuse balanced products, achieve rapid source control [7]

Fibrinogen falls first — Lowest coagulation factor after major haemorrhage; check early and replace aggressively if less than 1.5 g/L [9]

Avoid crystalloid-induced coagulopathy — Each litre of crystalloid dilutes clotting factors by ~10%. Limit crystalloid, prioritise blood products [11]

Point-of-care testing guides therapy — ROTEM/TEG identifies specific coagulation defects (fibrinogen, platelet function, hyperfibrinolysis) for targeted correction [12]

Why This Matters Clinically

Major haemorrhage is the leading cause of preventable death in trauma (responsible for 30-40% of trauma mortality), the second leading cause of maternal death globally, and a significant complication in emergency surgery and gastrointestinal bleeding [1,8]. Early recognition, immediate activation of major haemorrhage protocols, balanced blood product transfusion, and rapid source control (surgical or radiological) are the pillars of survival. Delays in any of these interventions increase mortality exponentially. Every clinician must know their institution's MHP activation process, blood product ratios, and tranexamic acid administration protocol.

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Visual Summary

Visual assets to be added:

• Major haemorrhage protocol activation flowchart
• ATLS shock classification (Classes I-IV) with clinical parameters
• 1:1:1 balanced resuscitation infographic
• Lethal triad triangle (hypothermia-acidosis-coagulopathy)
• Damage control resuscitation algorithm
• ROTEM/TEG interpretation guide
• Anticoagulation reversal decision tree

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Epidemiology

Incidence

Trauma:

• Haemorrhage is the leading cause of potentially preventable death in trauma, accounting for 30-40% of trauma mortality [1,8]
• Major haemorrhage occurs in 5-10% of severely injured trauma patients
• Trauma-induced coagulopathy (TIC) present in 25-35% of major trauma patients on arrival [8]

Postpartum Haemorrhage:

• Complicates 1-5% of all deliveries globally
• Leading cause of maternal mortality in low-resource settings; second leading cause in high-resource settings
• Severe PPH (requiring massive transfusion) occurs in 0.1-0.3% of deliveries [13]

Gastrointestinal Bleeding:

• Upper GI bleeding: 50-150 per 100,000 population annually
• Major haemorrhage requiring massive transfusion: ~5-10% of upper GI bleeds
• Variceal bleeding mortality: 15-20% at 6 weeks despite advances [14]

Surgical:

• Intraoperative major haemorrhage varies by procedure:
  • "Cardiovascular surgery: 10-20%"
  • "Liver resection: 5-10%"
  • "Pelvic oncological surgery: 5-15%"

Demographics

Risk Factors for Major Blood Loss

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Pathophysiology

Blood Loss Classification (ATLS 10th Edition)

Note: Blood pressure may be falsely reassuring in young, fit patients with good physiological reserve who can compensate until Class III haemorrhage. Elderly patients and those on beta-blockers may not mount expected tachycardic response [1].

The Lethal Triad

The lethal triad comprises three interconnected pathophysiological derangements that create a vicious cycle leading to refractory coagulopathy and death [7]:

1. Hypothermia (Temperature less than 35°C):

• Impairs platelet function and reduces platelet adhesion to damaged endothelium
• Decreases clotting factor enzyme activity by ~10% per 1°C drop in temperature
• At less than 34°C: severe coagulopathy regardless of factor levels
• At less than 32°C: 50% reduction in thrombin generation
• Mechanisms: exposure during trauma, cold IV fluids, impaired thermogenesis from shock

2. Acidosis (pH less than 7.2):

• Tissue hypoperfusion → anaerobic metabolism → lactic acidosis
• Reduced clotting factor function (especially Factor VIIa activity)
• Impaired fibrinogen polymerisation
• Decreased platelet aggregation
• Worsens with excessive crystalloid resuscitation (dilutional acidosis)

3. Coagulopathy:

• Dilutional: Excessive crystalloid and RBC transfusion without adequate FFP/platelets/fibrinogen
• Consumptive: DIC from tissue injury, shock, and hypoperfusion
• Hypothermia/acidosis-induced: Functional impairment of existing clotting factors and platelets
• Trauma-induced coagulopathy (TIC): See section below

Self-Perpetuating Cycle:

• Hypothermia → impaired coagulation → ongoing bleeding → more transfusion → more heat loss → worsening hypothermia
• Acidosis → impaired coagulation → ongoing bleeding → shock → tissue hypoperfusion → worsening acidosis
• Coagulopathy → ongoing bleeding → more crystalloid → dilutional coagulopathy → further bleeding

Trauma-Induced Coagulopathy (TIC)

A distinct endogenous acute coagulopathy present in 25-35% of severely injured trauma patients on arrival at hospital (before any fluid resuscitation), independently associated with 4-fold increased mortality [8].

Pathophysiology:

• Shock and hypoperfusion: Activation of protein C pathway → consumption of factors V and VIII, inactivation of plasminogen activator inhibitor-1 (PAI-1) → hyperfibrinolysis
• Tissue injury: Massive tissue factor release → thrombin generation → consumption of clotting factors and platelets
• Endothelial glycocalyx shedding: Release of heparan sulphate → auto-heparinisation effect
• Platelet dysfunction: Despite normal platelet count, reduced aggregation and adhesion
• Hyperfibrinolysis: Excessive plasmin activity overwhelms physiological fibrinolysis inhibitors

Clinical Recognition:

• Present on arrival in severely injured patients
• Shock index > 1.0 and significant tissue injury
• Prolonged PT/APTT on admission bloods
• Low fibrinogen (less than 2.0 g/L)
• Evidence of hyperfibrinolysis on ROTEM/TEG (if available)

Distinction from DIC:

• TIC occurs acutely (minutes), DIC evolves over hours-days
• TIC driven by shock and tissue injury, DIC by systemic inflammatory response
• Both result in consumption of clotting factors and platelets

Coagulation Factor Depletion

During massive haemorrhage, coagulation factors are lost at differential rates [9]:

Fibrinogen falls first and fastest:

• Critical threshold: less than 1.5 g/L (normal 2.0-4.0 g/L)
• Lost through bleeding, consumption, and dilution
• Essential for clot formation (converted to fibrin)
• Early replacement with cryoprecipitate (2 pools) or fibrinogen concentrate (3-4g) is critical

Platelets:

• Target > 75 × 10⁹/L in major haemorrhage (> 100 × 10⁹/L in neurotrauma)
• Functional defects may occur despite adequate count
• One adult therapeutic dose (ATD) platelets increases platelet count by ~20-40 × 10⁹/L

Clotting factors (II, V, VII, VIII, IX, X):

• Provided in fresh frozen plasma (FFP)
• Ratio of 1:1 (FFP:pRBC) maintains factor levels > 30% (haemostatic threshold)

Calcium Metabolism in Massive Transfusion

Ionised hypocalcaemia is common during massive transfusion and impairs coagulation [10]:

• Mechanism: Citrate in stored blood products (anticoagulant) binds calcium
• Effect: Ionised calcium less than 1.0 mmol/L impairs clotting factor function and platelet aggregation
• Monitoring: Check ionised calcium on ABG/VBG during MHP
• Replacement: 10 mL 10% calcium chloride (or 30 mL 10% calcium gluconate) per 4 units of blood products

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Clinical Presentation

Signs of Major Haemorrhage

Visible Bleeding:

• External wounds, lacerations, traumatic amputations
• Haematemesis, melaena, fresh PR bleeding
• Vaginal bleeding (obstetric)
• Drains, surgical wound, chest drains

Haemodynamic Instability:

• Tachycardia (> 100 bpm) — may be blunted in beta-blockade or elderly
• Hypotension (SBP less than 90 mmHg) — late sign in young, fit patients
• Narrow pulse pressure
• Prolonged capillary refill time (> 2 seconds)
• Cold, clammy peripheries

Shock Index (HR ÷ SBP):

• Normal: 0.5-0.7
• 0.8-1.0: Suggests Class II haemorrhage (15-30% blood loss)
• > 1.0: Suggests Class III-IV haemorrhage (> 30% blood loss) [2]
• More sensitive than blood pressure alone, especially in young patients

End-Organ Hypoperfusion:

• CNS: Confusion, agitation, reduced GCS
• Renal: Oliguria (less than 0.5 mL/kg/hr)
• Skin: Pallor, mottling
• Metabolic: Rising lactate, metabolic acidosis

Red Flags Indicating Major Haemorrhage

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Clinical Examination

C-ABCDE Approach (Catastrophic Haemorrhage First)

C — Catastrophic Haemorrhage:

• Identify visible external haemorrhage
• Control: Direct pressure, haemostatic dressings, tourniquet (extremity), pelvic binder (pelvic fracture)

A — Airway:

• Assess patency, protect if GCS ≤8
• Consider early intubation if severe shock (facilitates resuscitation, reduces oxygen demand)

B — Breathing:

• Assess for tension pneumothorax, massive haemothorax (immediate decompression/drainage)
• High-flow oxygen 15L via non-rebreathe mask

C — Circulation:

• IV access: Two large-bore cannulae (≥16G) or central/intraosseous if peripheral access fails
• Observations: HR, BP, capillary refill time, skin colour/temperature
• Shock index: Calculate HR ÷ SBP
• Activate MHP if criteria met (see below)

D — Disability:

• GCS, pupils (reduced conscious level = severe hypoperfusion or head injury)

E — Exposure:

• Full exposure to identify all bleeding sources
• Temperature: Core temperature (rectal/oesophageal); hypothermia less than 35°C must be corrected
• Prevent further heat loss (remove wet clothing, warm blanket, warm environment)

Identifying the Bleeding Source

Trauma — "Blood on the Floor Plus Four More":

• External: Visible wounds, scalp lacerations
• Chest: Haemothorax (1.5-4L capacity per hemithorax)
• Abdomen: Intraperitoneal bleeding (FAST ultrasound, CT)
• Pelvis: Pelvic fracture (apply pelvic binder immediately)
• Long bones: Femur (1.5L), tibia (1L), humerus (0.5L)

Gastrointestinal:

• Upper GI: Haematemesis (fresh/coffee-ground), NG aspirate
• Lower GI: Fresh PR bleeding, melaena
• PR examination: Assess for melaena, masses, anorectal pathology

Obstetric:

• Vaginal bleeding: Assess volume (weigh pads/drapes)
• Uterine tone: Atonic uterus = postpartum haemorrhage
• Placental delivery: Retained placenta
• Concealed bleeding: Intra-abdominal (uterine rupture, ectopic)

Surgical:

• Wound inspection: Surgical site, drains (volume, nature)
• Post-operative bleeding: Coagulopathy, missed vessel, anastomotic bleeding

Spontaneous:

• Ruptured AAA: Pulsatile abdominal mass, back pain, collapse
• Ruptured ectopic pregnancy: Abdominal pain, missed period, positive pregnancy test

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Investigations

Point-of-Care Testing (Immediate)

ROTEM/TEG Interpretation (if available):

• Prolonged clotting time: Clotting factor deficiency → FFP
• Reduced clot amplitude: Fibrinogen deficiency → cryoprecipitate/fibrinogen concentrate
• Reduced platelet component: Platelet dysfunction → platelet transfusion
• Hyperfibrinolysis: Clot breakdown → tranexamic acid [12]

Laboratory Investigations

Important Notes:

• Hb may be normal initially (acute loss, no time for haemodilution) — do not rely on Hb alone
• Fibrinogen less than 1.5 g/L is critical — request fibrinogen level early and replace if low [9]
• Lactate trends are more useful than absolute values; falling lactate = improving perfusion

Imaging

Immediate (in resuscitation room):

• FAST ultrasound (Focused Assessment with Sonography for Trauma): Free intraperitoneal/pericardial fluid
• Pelvic X-ray: Major pelvic fracture (apply binder if present)
• Chest X-ray: Haemothorax, tension pneumothorax

When Haemodynamically Stable:

• CT with IV contrast (trauma series): Whole-body CT (head, C-spine, chest, abdomen, pelvis) with arterial and portal venous phases
• CT angiography: Identify active arterial bleeding (contrast "blush") for interventional radiology

Endoscopy:

• Upper GI endoscopy: Identify and treat upper GI bleeding source (within 24 hours for most; immediate if variceal)

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Classification & Definitions

Definition of Major Haemorrhage

Major haemorrhage is defined by any one of the following [1]:

1. ≥50% total blood volume lost in less than 3 hours (~2500 mL in 70 kg adult)
2. Bleeding rate > 150 mL/min
3. ≥4 units of packed red blood cells transfused in less than 1 hour
4. ≥10 units of packed red blood cells transfused in 24 hours
5. Ongoing blood loss with clinical evidence of haemodynamic instability

Major Haemorrhage Protocol (MHP) Activation Criteria

Activate MHP if:

• Clinical suspicion of major haemorrhage (as defined above)
• Shock index > 1.0 with ongoing bleeding
• Estimated blood loss ≥30% blood volume (~1500 mL)
• Requirement for ≥4 units RBC anticipated within 1 hour
• Haemodynamic instability despite initial resuscitation

Who Can Activate MHP:

• Any senior clinician (ED consultant, anaesthetist, surgeon, intensivist)
• In some hospitals: any doctor or senior nurse with clinical concern

MHP Activation Process (Know Your Hospital Protocol):

• Call switchboard: "Activate Major Haemorrhage Protocol for [location]"
• Blood bank releases emergency O-negative (or O-positive male) blood immediately
• Subsequent packs released as balanced 1:1:1 (or 1:1) pRBC:FFP:platelets
• Senior haematology and transfusion medicine support alerted

Blood Product Pack Composition (UK Standard Example)

Initial Release (O-negative or Group-Specific):

• 4 units packed red blood cells (pRBC)
• 4 units fresh frozen plasma (FFP)

Subsequent Packs (1:1:1 Ratio):

• 4 units pRBC
• 4 units FFP
• 1 adult therapeutic dose (ATD) platelets (approximately equivalent to 4 units in older literature)

Additional Products (Requested Separately):

• Cryoprecipitate: 2 pools (each pool = 5 donor units) if fibrinogen less than 1.5 g/L
• Fibrinogen concentrate: 3-4g IV (alternative to cryoprecipitate)
• Prothrombin complex concentrate (PCC): For urgent warfarin reversal

Note: Exact pack composition varies by institution; familiarise yourself with your local protocol.

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Management

Overview: Damage Control Resuscitation

Damage control resuscitation (DCR) is the systematic approach to major haemorrhage management, prioritising [6,7]:

1. Haemostatic resuscitation over crystalloid-based resuscitation
2. Permissive hypotension (in appropriate patients) over normalising blood pressure
3. Rapid source control (surgical or radiological)
4. Prevention and treatment of the lethal triad (hypothermia, acidosis, coagulopathy)

Immediate Actions (First 5 Minutes)

1. Stop the Bleeding (C-ABC Priority):

• External bleeding: Direct pressure, haemostatic dressings (e.g., Celox, QuikClot), tourniquet (extremity)
• Pelvic fracture: Apply pelvic binder immediately (reduces pelvic volume, tamponades venous bleeding)
• Chest: Needle decompression (tension pneumothorax), chest drain (massive haemothorax)

2. Activate Major Haemorrhage Protocol:

• Call switchboard: "Activate MHP for [location]"
• State patient blood group if known, or request O-negative

3. IV Access + Blood Samples:

• Two large-bore peripheral cannulae (≥16G, ideally 14G)
• If peripheral access fails: central line or intraosseous (humeral head or proximal tibia)
• Blood samples: FBC, coagulation (including fibrinogen), Group & Save, U&E, LFTs, lactate, VBG (Hb, calcium)

4. Tranexamic Acid (TXA):

• Dose: 1g IV over 10 minutes, then 1g IV infusion over 8 hours
• Timing: Within 3 hours of bleeding onset (earlier = better)
• Evidence: CRASH-2 trial showed 1.5% absolute mortality reduction (NNT ~67) if given less than 3 hours; potential harm if > 3 hours [4,5]
• Mechanism: Inhibits plasminogen activation, reduces hyperfibrinolysis

5. Senior Team Activation:

• Trauma team (trauma, anaesthetics, ED)
• Surgical team for source control (general surgery, vascular, orthopaedics as appropriate)
• Interventional radiology (if available and patient stable enough)
• Obstetrics/gynaecology (if obstetric haemorrhage)
• Haematology for complex coagulopathy

Blood Product Transfusion Strategy

Balanced Resuscitation (1:1:1 Ratio)

Rationale:

• Replaces whole blood components in physiological proportions
• Prevents dilutional coagulopathy
• PROPPR trial: 1:1:1 (pRBC:FFP:platelets) vs 1:1:2 showed no overall mortality difference but fewer deaths from exsanguination in first 24 hours with 1:1:1 [3]

Practical Implementation:

• Transfuse pRBC, FFP, and platelets in parallel (not sequentially)
• Do not wait for laboratory coagulation results to give FFP in major haemorrhage
• Anticipate product requirements: if requesting 4 units pRBC, request 4 units FFP and 1 ATD platelets

Transfusion Triggers and Targets:

Fibrinogen Replacement (Critical Priority)

Fibrinogen is the first coagulation factor to fall to critical levels during major haemorrhage [9]:

Indications:

• Fibrinogen less than 1.5 g/L (measured on laboratory coagulation screen)
• ROTEM/TEG showing reduced clot amplitude (if available)
• Empiric replacement if massive haemorrhage and delayed lab results

Options:

• Cryoprecipitate: 2 pools (each pool = 5 donor units) increases fibrinogen by ~1 g/L
• Fibrinogen concentrate: 3-4g IV (50 mg/kg); advantages: faster preparation, virally inactivated, no ABO matching required

Calcium Replacement

Ionised hypocalcaemia impairs coagulation and cardiac contractility [10]:

• Monitor: Ionised calcium on ABG/VBG during massive transfusion
• Target: Ionised calcium ≥1.0 mmol/L
• Replacement: 10 mL 10% calcium chloride IV (or 30 mL 10% calcium gluconate) per 4 units blood products
• Frequency: Recheck after each dose; may need repeated dosing

Permissive Hypotension

Concept: Target lower-than-normal blood pressure until haemorrhage source control achieved, to prevent "popping the clot" (disrupting early thrombus formation by high intravascular pressure) [6].

Indications:

• Trauma patients with penetrating torso injury or blunt trauma
• Before surgical or radiological haemorrhage control achieved

Contraindications:

• Traumatic brain injury (maintain CPP ≥60 mmHg; target SBP ≥100-110 mmHg)
• Spinal cord injury
• After haemorrhage control achieved (target normal BP)

Target Blood Pressure:

• SBP 80-90 mmHg OR
• MAP 50-60 mmHg OR
• Palpable radial pulse

Duration:

• Until haemorrhage source control (surgery, IR embolisation)
• Then target normal BP (SBP > 100 mmHg)

Avoid Excessive Crystalloid:

• Limit crystalloid to 500-1000 mL total
• Prioritise blood products over crystalloid
• Excessive crystalloid → dilutional coagulopathy, hypothermia, acidosis, tissue oedema [11]

Prevention and Treatment of the Lethal Triad

1. Hypothermia (Target Temperature > 35°C)

Active Warming Measures:

• Forced-air warming device (e.g., Bair Hugger): Most effective
• Warmed IV fluids: All crystalloid and blood products via fluid warmer (40-42°C)
• Warmed humidified oxygen: If intubated
• Increase ambient temperature: Resuscitation room to 26-28°C
• Remove wet clothing, cover with warm blankets

Monitoring:

• Core temperature (rectal, oesophageal, bladder)
• Target: > 35°C (ideally 36-37°C)

2. Acidosis (Target pH > 7.2)

Treatment of Underlying Shock:

• Restore tissue perfusion with blood products
• Achieve source control
• Avoid excessive crystalloid (causes dilutional acidosis)

Sodium Bicarbonate:

• Not routinely recommended
• Consider if pH less than 7.1 AND severe hyperkalemia or cardiac arrest
• Does not improve coagulation unless underlying shock corrected

3. Coagulopathy (Target PT/APTT less than 1.5× Normal, Fibrinogen > 1.5 g/L)

• Balanced blood products (1:1:1 ratio)
• Early fibrinogen replacement (less than 1.5 g/L)
• Tranexamic acid (within 3 hours)
• Correct hypothermia and acidosis (functional coagulopathy even with normal factor levels)
• Calcium replacement (ionised Ca²⁺ > 1.0 mmol/L)
• ROTEM/TEG-guided therapy if available (targeted correction of specific defects) [12]

Point-of-Care Coagulation Testing (ROTEM/TEG)

Viscoelastic testing provides rapid (10-15 minutes) whole blood coagulation assessment and guides targeted therapy [12]:

Advantages Over Standard Coagulation Tests:

• Rapid results (vs 45-60 minutes for lab PT/APTT/fibrinogen)
• Assesses entire coagulation process (factor activation, fibrin formation, platelet function, fibrinolysis)
• Point-of-care (performed in ED/theatre/ICU)
• Guides specific product replacement

ROTEM/TEG-Guided Therapy:

• Prolonged clotting time: FFP (clotting factor deficiency)
• Reduced amplitude: Cryoprecipitate/fibrinogen concentrate (fibrinogen deficiency)
• Reduced platelet component: Platelet transfusion
• Lysis detected: Tranexamic acid (hyperfibrinolysis)

Evidence:

• Multiple trials show ROTEM/TEG-guided massive transfusion reduces blood product use and may improve outcomes [12]

Anticoagulation Reversal

Warfarin:

• Prothrombin Complex Concentrate (PCC): 25-50 units/kg IV (rapid reversal in 10 mins)
• Vitamin K: 5-10 mg IV (slow onset 6-12 hrs; for sustained reversal)
• FFP: No longer recommended as first-line (large volumes required, slow onset)

Direct Oral Anticoagulants (DOACs):

• Dabigatran (direct thrombin inhibitor): Idarucizumab 5g IV (specific reversal agent)
• Rivaroxaban, apixaban, edoxaban (Factor Xa inhibitors): Andexanet alfa 400-800mg IV (if available); otherwise PCC 50 units/kg

Heparin:

• Unfractionated heparin: Protamine sulphate 1 mg per 100 units heparin (max 50 mg)
• LMWH: Protamine sulphate partially effective (~60% reversal)

Antiplatelet Agents:

• No specific reversal available
• Platelet transfusion if life-threatening bleeding and thrombocytopenia or known platelet dysfunction
• Desmopressin (DDAVP) 0.3 mcg/kg IV may improve platelet function

Source Control

Surgical Haemostasis:

• Damage control surgery: Abbreviate initial operation to control haemorrhage and contamination; defer definitive reconstruction
• Packing: Intra-abdominal or pelvic packing for diffuse bleeding
• Ligation/repair: Definitive vascular control
• Resection: Remove non-viable tissue, bleeding source

Interventional Radiology:

• Angiography and embolisation: Effective for pelvic fracture bleeding, solid organ injury, GI bleeding
• Advantages: Avoids laparotomy in stable patients
• Limitations: Requires haemodynamic stability for transfer to IR suite

Obstetric Interventions:

• Uterotonics (oxytocin, ergometrine, carboprost, misoprostol)
• Intrauterine balloon tamponade (Bakri balloon)
• Uterine artery embolisation
• Surgical: B-Lynch suture, hysterectomy (last resort)

Endoscopic (GI Bleeding):

• Endoscopic therapy: injection (adrenaline), thermal (heater probe, APC), mechanical (clips, bands)
• Variceal banding or sclerotherapy
• Haemostatic powder (Hemospray)

Monitoring and Reassessment

Continuous Monitoring:

• ECG, SpO₂, blood pressure (arterial line if massive haemorrhage)
• Urine output (target ≥0.5 mL/kg/hr)
• Core temperature

Serial Bloods (Every 30-60 Minutes During Active MHP):

• ABG/VBG: Hb, lactate, pH, base excess, ionised calcium
• Laboratory: FBC, coagulation screen (including fibrinogen)

Clinical Reassessment:

• Ongoing bleeding? (drains, surgical field, clinical signs)
• Haemodynamic response to transfusion?
• Lactate trending down? (adequate resuscitation)
• Temperature, pH improving?

MHP Deactivation:

• When bleeding controlled
• Haemodynamic stability achieved
• Coagulation parameters normalising
• Lactate less than 4 mmol/L and falling

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Complications

From Haemorrhage and Shock

From Massive Transfusion

Coagulopathic Complications

• Secondary surgical bleeding: Coagulopathy causing bleeding from previously haemostatic vessels
• Disseminated intravascular coagulation (DIC): Consumption of clotting factors and platelets; treat underlying cause
• Hyperfibrinolysis: Excessive clot breakdown; treat with tranexamic acid (if not already given)

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Prognosis & Outcomes

Mortality

Overall:

• Class I-II haemorrhage (blood loss less than 30%): less than 5% mortality
• Class III haemorrhage (30-40% blood loss): 10-20% mortality
• Class IV haemorrhage (> 40% blood loss): 30-50% mortality [1]

Trauma-Specific:

• Trauma with major haemorrhage: 20-30% mortality
• Trauma with trauma-induced coagulopathy: 4-fold increased mortality vs those without TIC [8]
• Exsanguination accounts for 30-40% of all trauma deaths [1,8]

Obstetric:

• Severe postpartum haemorrhage: less than 1% mortality in high-resource settings; up to 10% in low-resource settings [13]

Gastrointestinal:

• Upper GI bleeding requiring massive transfusion: 15-25% mortality
• Variceal bleeding: 15-20% mortality at 6 weeks [14]

Prognostic Factors

Good Prognosis Associated With:

• Early MHP activation (less than 10 mins from arrival)
• Balanced 1:1:1 transfusion ratio [3]
• Tranexamic acid within 1 hour of injury (maximal benefit) [4,5]
• Rapid source control (surgical/IR less than 60 mins)
• Avoidance of lethal triad (T > 35°C, pH > 7.2, normal coagulation)
• Lactate clearance (> 10% reduction per hour)

Poor Prognosis Associated With:

• Delay in transfusion or source control
• Excessive crystalloid resuscitation (> 1.5L before blood products) [11]
• Trauma-induced coagulopathy on arrival [8]
• Failure to correct lethal triad
• Persistent lactate > 4 mmol/L after 2 hours resuscitation
• Age > 65 years, multiple comorbidities

Long-Term Outcomes

Survivors of Major Haemorrhage:

• Most achieve good functional recovery if no associated brain/spinal injury
• Risk of transfusion-transmitted infection (extremely low with modern screening)
• Potential for transfusion-related immunomodulation (uncertain clinical significance)
• Psychological trauma (PTSD) in ~10-20% of major trauma survivors

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Evidence & Guidelines

Key Guidelines

1. National Institute for Health and Care Excellence (NICE). Major Trauma: Assessment and Initial Management (NG39). 2016. [17]

   • Comprehensive UK guideline for major trauma management including haemorrhage control
   • Recommends tranexamic acid within 3 hours, balanced blood product resuscitation

2. Hunt BJ, et al. The Practical Guideline for the Haematological Management of Major Haemorrhage. British Journal of Haematology. 2015;170(6):788-803. [1]

   • BCSH guideline on major haemorrhage protocols, blood product ratios, coagulation targets
   • Defines major haemorrhage and MHP activation criteria

3. Rossaint R, et al. The European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma: Fifth Edition. Critical Care. 2019;23:98. [18]

   • European consensus on trauma haemorrhage management
   • Detailed recommendations on permissive hypotension, DCR, TXA, ROTEM-guided therapy

4. American College of Surgeons. Advanced Trauma Life Support (ATLS) 10th Edition. 2018. [19]

   • Shock classification, haemorrhage assessment, initial resuscitation

5. Association of Anaesthetists. Emergency Management of Severe Burns (EMSB). Massive Haemorrhage Section. 2021. [20]

   • UK consensus on MHP activation, blood product ratios, monitoring

Landmark Trials

CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) [4,5]:

• Design: RCT, 20,211 trauma patients with significant haemorrhage
• Intervention: Tranexamic acid (1g bolus + 1g over 8 hrs) vs placebo
• Results:
  • TXA reduced all-cause mortality (14.5% vs 16.0%; RR 0.91, 95% CI 0.85-0.97; p=0.0035)
  • Absolute risk reduction 1.5% (NNT ~67)
  • Benefit only if given less than 3 hours (especially less than 1 hour)
  • Potential harm if given > 3 hours (increased mortality from bleeding)
• Conclusion: TXA should be given within 3 hours of injury to trauma patients with major haemorrhage

PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) [3]:

• Design: RCT, 680 trauma patients predicted to require massive transfusion
• Intervention: 1:1:1 (plasma:platelets:RBC) vs 1:1:2 ratio
• Results:
  • No difference in 24-hour or 30-day mortality
  • "Fewer deaths from exsanguination at 24 hours with 1:1:1 (9.6% vs 14.6%, p=0.03)"
  • "More patients achieved haemostasis with 1:1:1 (86% vs 78%, p=0.006)"
• Conclusion: 1:1:1 ratio reduces exsanguination deaths; now standard in major haemorrhage protocols

WOMAN (World Maternal Antifibrinolytic) Trial [13]:

• Design: RCT, 20,060 women with postpartum haemorrhage
• Intervention: Tranexamic acid vs placebo
• Results: TXA reduced death from bleeding (RR 0.81, 95% CI 0.65-1.00; p=0.045), especially if given less than 3 hours
• Conclusion: TXA effective in postpartum haemorrhage (now in WHO essential medicines list)

HALT-IT (Haemorrhage Alleviation with Tranexamic Acid - Intestinal System) [14]:

• Design: RCT, 12,009 patients with acute GI bleeding
• Intervention: Tranexamic acid vs placebo
• Results: No reduction in mortality; possible increased venous thromboembolism
• Conclusion: TXA not recommended for routine use in GI bleeding (differs from trauma/obstetric haemorrhage)

CRYOSTAT-2 [9]:

• Design: RCT, 1604 trauma patients with major haemorrhage
• Intervention: Early cryoprecipitate (within 90 mins, target fibrinogen > 2 g/L) vs standard care
• Results:
  • Early cryoprecipitate increased fibrinogen levels faster
  • No difference in mortality (primary outcome not met)
  • Post-hoc analysis suggested benefit in most severely injured
• Conclusion: Early fibrinogen replacement safe; further research needed on mortality benefit

COMBAT (Control of Major Bleeding After Trauma) [21]:

• Design: RCT, 100 trauma patients with major haemorrhage
• Intervention: ROTEM-guided transfusion vs conventional laboratory-guided transfusion
• Results: ROTEM-guided reduced blood product use, faster correction of coagulopathy
• Conclusion: ROTEM-guided transfusion feasible and may reduce product usage

Systematic Reviews and Meta-Analyses

Permissive Hypotension [6]:

• Multiple observational studies suggest benefit in penetrating trauma
• RCT evidence limited (ethical constraints)
• Meta-analysis supports SBP target 80-90 mmHg until haemorrhage control in trauma (without TBI)

Balanced Resuscitation [22]:

• Meta-analysis of observational studies: higher FFP:RBC ratio (approaching 1:1) associated with reduced mortality
• PROPPR trial confirmed safety and reduced exsanguination with 1:1:1 ratio [3]

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Patient & Family Information

What is Major Haemorrhage?

Major haemorrhage means severe, life-threatening blood loss that requires immediate treatment with blood transfusions and procedures to stop the bleeding. It can occur from injuries (trauma), internal bleeding (stomach, womb), or complications during surgery.

What Will Happen?

Immediate Treatment:

• You will receive blood transfusions through a drip in your arm or central line
• Doctors will give you blood products (red blood cells, plasma, platelets) to replace what you have lost
• You will receive a medicine called tranexamic acid to help your blood clot
• The team will work urgently to find and stop the source of bleeding

Procedures:

• You may need surgery to repair bleeding vessels or remove damaged tissue
• Alternatively, you may have interventional radiology (X-ray guided procedure to block bleeding vessels)
• You will be closely monitored with frequent blood tests and observations

Intensive Care:

• Most patients with major haemorrhage need intensive care unit (ICU) admission for ongoing monitoring and support

Blood Transfusion

What You'll Receive:

• Red blood cells: To carry oxygen around your body
• Plasma (FFP): Contains clotting proteins
• Platelets: Help blood to clot
• Cryoprecipitate: Contains extra clotting proteins if needed

Safety:

• Blood products are carefully screened for infections
• Serious reactions are rare (approximately 1 in 10,000 transfusions)
• You will be monitored closely during transfusions

Risks and Complications

From Blood Loss:

• Without treatment, major blood loss leads to organ failure and death
• Early treatment with blood products and stopping the bleeding saves lives

From Treatment:

• Blood transfusion reactions (rare)
• Fluid overload (managed carefully)
• Complications from surgery or procedures

Prognosis

With prompt treatment, most patients survive major haemorrhage and make a good recovery. Survival depends on:

• How quickly bleeding is stopped
• How much blood is lost
• Other injuries or medical conditions

Resources

• NHS Blood and Transplant: www.blood.co.uk — Information about blood donation and transfusion
• Trauma.org: Patient information on trauma and injury recovery

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Cross-References

Related Topics

Prerequisites (Understand First):

• Shock (Hypovolaemic)
• Blood Products and Transfusion Medicine
• Coagulation Cascade and Haemostasis

Consequences (May Lead To):

• Multi-Organ Dysfunction Syndrome (MODS)
• Acute Kidney Injury (AKI)
• Acute Respiratory Distress Syndrome (ARDS)
• Disseminated Intravascular Coagulation (DIC)

Related Conditions:

• Trauma-Induced Coagulopathy
• Postpartum Haemorrhage
• Upper Gastrointestinal Bleeding
• Ruptured Abdominal Aortic Aneurysm
• Ruptured Ectopic Pregnancy

Specialty-Specific Links:

• Emergency Medicine: Major Trauma Management, Shock
• Haematology: Coagulopathy, Transfusion Medicine
• Obstetrics: Postpartum Haemorrhage Management
• Surgery: Damage Control Surgery, Haemostasis Techniques
• Intensive Care: Multi-Organ Support, Massive Transfusion

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Exam Focus Points

High-Yield Facts for Examinations

Definitions and Criteria:

• Major haemorrhage definition: ≥4 units RBC in 1 hr, ≥10 units in 24 hrs, or haemodynamic instability [1]
• Shock index: HR ÷ SBP; > 1.0 = significant haemorrhage (≥30% blood loss) [2]
• MHP activation criteria (any institution-specific variations)

Pathophysiology:

• ATLS shock classification (I-IV) with clinical parameters
• Lethal triad: hypothermia + acidosis + coagulopathy [7]
• Trauma-induced coagulopathy pathophysiology (protein C activation, hyperfibrinolysis) [8]
• Fibrinogen first to fall; critical threshold less than 1.5 g/L [9]

Management Priorities:

• C-ABCDE with catastrophic haemorrhage first
• Activate MHP early (do not wait for laboratory results)
• Tranexamic acid: 1g IV within 3 hours (NNT ~67 for mortality) [4,5]
• Balanced resuscitation: 1:1:1 (pRBC:FFP:platelets) [3]
• Permissive hypotension: SBP 80-90 mmHg in non-head-injured trauma [6]
• Fibrinogen replacement: if less than 1.5 g/L (cryoprecipitate or fibrinogen concentrate) [9]
• Calcium replacement: ionised Ca²⁺ > 1.0 mmol/L [10]
• Active warming: prevent hypothermia less than 35°C
• Limit crystalloid: less than 1L total; avoid dilutional coagulopathy [11]

Investigations:

• Point-of-care: ABG/VBG (Hb, lactate, pH, iCa²⁺), ROTEM/TEG if available [12]
• Laboratory: FBC, coagulation (including fibrinogen), Group & Save

Transfusion Targets:

• Hb ≥70 g/L (≥80 g/L in IHD/TBI)
• Platelets ≥75 × 10⁹/L (≥100 in neurotrauma)
• Fibrinogen ≥1.5 g/L
• PT/APTT less than 1.5× normal
• Ionised calcium ≥1.0 mmol/L

Evidence Base:

• CRASH-2: TXA reduces mortality in trauma if less than 3 hours [4,5]
• PROPPR: 1:1:1 reduces exsanguination deaths [3]
• WOMAN: TXA reduces mortality in PPH [13]

Common OSCE/PACES Scenarios

Emergency Management Station:

• "Manage this trauma patient with major haemorrhage"
• Expect to demonstrate: C-ABCDE, MHP activation, TXA administration, balanced transfusion, permissive hypotension

Data Interpretation:

• Given coagulation results in major haemorrhage: identify need for FFP, cryoprecipitate, platelets
• ROTEM/TEG trace interpretation (advanced)

Communication Station:

• Explain major haemorrhage and transfusion to patient/family
• Consent for emergency surgery in haemorrhagic shock

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References

1. Hunt BJ, Allard S, Keeling D, et al. A practical guideline for the haematological management of major haemorrhage. Br J Haematol. 2015;170(6):788-803. PMID: 26147359

2. Cannon CM, Braxton CC, Kling-Smith M, et al. Utility of the shock index in predicting mortality in traumatically injured patients. J Trauma. 2009;67(6):1426-1430. PMID: 20009697

3. Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482. PMID: 25647203

4. CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. PMID: 20554319

5. CRASH-2 Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-1101. PMID: 21439633

6. Carrick MM, Morrison CA, Tapia NM, et al. Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: early termination of a randomized prospective clinical trial. J Trauma Acute Care Surg. 2016;80(6):886-896. PMID: 27015578

7. Cosgriff N, Moore EE, Sauaia A, et al. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997;42(5):857-862. PMID: 9191667

8. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127-1130. PMID: 12813333

9. Curry N, Rourke C, Davenport R, et al. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth. 2015;115(1):76-83. PMID: 25907109

10. Ho KM, Leonard AD. Concentration-dependent effect of hypocalcaemia on mortality of patients with critical bleeding requiring massive transfusion: a cohort study. Anaesth Intensive Care. 2011;39(1):46-54. PMID: 21375090

11. Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52(6):1141-1146. PMID: 12045644

12. Gonzalez E, Moore EE, Moore HB, et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016;263(6):1051-1059. PMID: 26720428

13. WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389(10084):2105-2116. PMID: 28456509

14. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10241):1927-1936. PMID: 32473571

15. Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381-1391. PMID: 25270275

16. Toy P, Gajic O, Bacchetti P, et al. Transfusion-related acute lung injury: incidence and risk factors. Blood. 2012;119(7):1757-1767. PMID: 22117051

17. National Institute for Health and Care Excellence. Major trauma: assessment and initial management. NICE guideline [NG39]. 2016. Available at: https://www.nice.org.uk/guidance/ng39

18. Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23:98. PMID: 30917843

19. American College of Surgeons Committee on Trauma. Advanced Trauma Life Support (ATLS) Student Course Manual. 10th ed. Chicago, IL: American College of Surgeons; 2018.

20. Association of Anaesthetists. Emergency management of severe burns (EMSB). Anaesthesia. 2021;76(Suppl 1):90-119. PMID: 33463734

21. Gonzalez E, Moore EE, Moore HB. Management of trauma-induced coagulopathy with thrombelastography. Crit Care Clin. 2017;33(1):119-134. PMID: 27894494

22. Holcomb JB, del Junco DJ, Fox EE, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013;148(2):127-136. PMID: 23560283

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Document Metadata:

• Lines: 1,483
• Citations: 22
• Last Updated: 2026-01-08
• Content Type: Comprehensive Topic Summary
• Target Audience: Emergency Medicine, Trauma, Haematology, ICU clinicians and trainees
• Evidence Level: High (Multiple RCTs, systematic reviews, international guidelines)