Blood Component Therapy

Quick Answer

Blood component therapy involves the transfusion of specific blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate) to correct particular deficiencies rather than using whole blood. This component approach maximizes the therapeutic benefit of donated blood while minimizing volume overload and unnecessary exposure to blood products. [1,2]

Key Transfusion Thresholds:

Landmark Evidence:

• TRICC Trial (1999): Restrictive (Hb 70 g/L) vs liberal (100 g/L) strategy showed no mortality difference; restrictive strategy reduced transfusions by 54% [3]
• TRISS Trial (2014): In septic shock, restrictive (Hb 70 g/L) showed lower mortality than liberal (90 g/L): 43% vs 45%, and fewer transfusions [4]
• TRICS-III (2017): Restrictive strategy non-inferior in cardiac surgery; composite outcome similar (11.4% vs 12.5%) [5]

Critical Complications:

• TRALI: Acute lung injury within 6 hours; non-cardiogenic pulmonary oedema; BNP normal/low [9]
• TACO: Circulatory overload; cardiogenic pulmonary oedema; BNP elevated; responds to diuretics [10]
• Febrile non-haemolytic reaction: Most common; cytokines in stored products [11]
• Acute haemolytic reaction: ABO incompatibility; stop transfusion immediately [12]

Australian Context: Australian Red Cross Lifeblood supplies all blood products in Australia. Pre-transfusion testing, compatibility testing, and blood product selection follow NBA guidelines. Indigenous Australians have higher rates of conditions requiring transfusion (renal disease, GI bleeding) and may have unique considerations including geographic isolation. [13,14]

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CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

Common SAQ stems:

• "A 72-year-old male post-CABG has Hb 68 g/L on Day 2. Discuss the evidence regarding transfusion thresholds and your approach to blood product therapy."
• "Outline the clinical features, investigation, and management of TRALI vs TACO."
• "A trauma patient is receiving massive transfusion. Describe the optimal ratio of blood products and the complications you would anticipate."
• "Describe the indications, dosing, and monitoring for FFP, platelets, and cryoprecipitate in the ICU."

Expected depth:

• Knowledge of landmark transfusion trials (TRICC, TRISS, TRICS-III, PROPPR)
• Understanding of blood component properties and storage
• Differentiation of TRALI vs TACO with diagnostic criteria
• Platelet transfusion thresholds in different clinical contexts
• Australian blood service processes and compatibility testing
• Complications of transfusion and their management

Second Part Hot Case:

Typical presentations:

• Post-operative patient with ongoing bleeding requiring component therapy
• Septic patient with coagulopathy requiring FFP/cryoprecipitate
• Patient with respiratory distress post-transfusion (TRALI vs TACO)
• Trauma patient on massive transfusion protocol

Examiners assess:

• Recognition of transfusion indications and appropriate thresholds
• Understanding of component selection and dosing
• Recognition and management of transfusion complications
• Communication with blood bank and haematology
• Documentation and adverse event reporting

Second Part Viva:

Expected discussion areas:

• Evidence base for restrictive vs liberal transfusion strategies
• Pathophysiology of storage lesion and its clinical significance
• TRALI vs TACO differentiation and management
• Platelet transfusion in various clinical contexts
• Massive transfusion ratios and damage control resuscitation
• Crossmatching, compatibility testing, and emergency transfusion
• Special populations (renal failure, cardiac surgery, trauma)

Examiner expectations:

• Cite key trials with PMIDs
• Demonstrate understanding of blood product physiology
• Show awareness of Australian blood service processes
• Discuss Indigenous health considerations
• Address resource stewardship

Common Mistakes

• Transfusing to arbitrary Hb targets rather than evidence-based thresholds
• Not recognizing the difference between TRALI and TACO
• Forgetting calcium replacement during massive transfusion
• Using FFP for INR correction without bleeding or procedure
• Not considering platelet dysfunction despite adequate count
• Transfusing platelets in HIT or TTP
• Inadequate documentation of transfusion indication
• Not checking compatibility in emergency situations

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Key Points

1. Restrictive transfusion (Hb 70 g/L): TRICC, TRISS, and TRICS-III trials support restrictive thresholds in most ICU populations; transfuse for Hb less than 70 g/L unless active cardiac ischaemia, massive haemorrhage, or symptomatic anaemia [3,4,5]

2. PRBC storage lesion: 2,3-DPG depletion, reduced deformability, microparticle release, potassium leak; clinical significance debated but older blood associated with inflammatory response [15,16]

3. FFP dosing: 10-15 mL/kg to achieve factor levels of 30%; one unit FFP increases factor levels by approximately 3-5%; INR >1.5 threshold for replacement [6,17]

4. Platelet thresholds: 10 × 10^9/L (prophylactic), 20 (sepsis/DIC), 50 (invasive procedures), 100 (neurosurgery/active bleeding) [7]

5. Cryoprecipitate: Contains fibrinogen (3 g per 5-unit pool), FVIII, FXIII, vWF, fibronectin; target fibrinogen >1.5 g/L; CRYOSTAT-2 supports early empiric use [8,18]

6. TRALI vs TACO: TRALI = ARDS pattern within 6h, normal/low BNP, no fluid overload; TACO = hydrostatic oedema, elevated BNP, responds to diuretics [9,10,19]

7. Massive transfusion 1:1:1: PROPPR trial showed 1:1:1 ratio (FFP:platelets:PRBC) reduces early death from exsanguination compared to 1:1:2 [20]

8. Crossmatching hierarchy: Emergency O-negative → Type-specific uncrossmatched → Abbreviated crossmatch (10 min) → Full crossmatch (45-60 min) [21]

9. Australian Red Cross Lifeblood: Sole supplier of blood products in Australia; group-and-save valid for 72 hours; electronic crossmatch available [13]

10. Indigenous health: Higher rates of transfusion-requiring conditions; geographic barriers; culturally appropriate consent processes essential [14,22]

Memory Aids

Platelet Threshold Mnemonic - "10-20-50-100":

• 10: Prophylactic (stable, no bleeding)
• 20: Sepsis, fever, DIC
• 50: Invasive procedures, minor surgery
• 100: Neurosurgery, eye surgery, active intracranial bleeding

TRALI vs TACO - "TRALI is DRY, TACO is WET":

• TRALI: No fluid overload, low BNP, ARDS pattern, does NOT respond to diuretics
• TACO: Fluid overload, high BNP, cardiogenic oedema, RESPONDS to diuretics

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Definitions and Epidemiology

Blood Component Definitions

Epidemiology of Blood Transfusion in ICU

Transfusion Rates:

• 40-60% of ICU patients receive at least one blood transfusion during their stay [28,29]
• Average 2-5 units PRBC per transfused patient
• Higher rates in cardiac surgery, trauma, and haematology/oncology ICUs

ABC Study (Anaemia and Blood Transfusion in Critical Care): European multicentre study showing:

• 37% of ICU patients transfused
• Mean pre-transfusion Hb 84 g/L (despite evidence for lower thresholds)
• Transfusion independently associated with worse outcomes after adjusting for severity [30]

CRIT Study: US observational study of 4,892 ICU patients:

• 44% received transfusion
• Mean 4.6 units per transfused patient
• Transfusion associated with increased ICU LOS, hospital LOS, and mortality [31]

Australian Data:

• Approximately 1.5 million blood component transfusions annually in Australia
• ICU accounts for approximately 15-20% of hospital PRBC usage
• NBA Patient Blood Management guidelines have reduced inappropriate transfusion [13,32]

High-Risk Populations

Aboriginal and Torres Strait Islander Peoples:

• Higher rates of chronic kidney disease (10-20× prevalence in remote areas)
• Higher rates of GI bleeding (peptic ulcer, portal hypertension)
• Higher rates of trauma
• Geographic isolation affects blood product availability
• Cultural considerations for transfusion consent
• May have rare blood group phenotypes requiring special matching [14,22]

Other Vulnerable Groups:

• Chronic transfusion recipients (haemoglobinopathies) - alloimmunization risk
• Jehovah's Witnesses - require bloodless medicine strategies
• Elderly - TACO risk increased
• Renal failure patients - uraemic platelet dysfunction

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Pathophysiology

Red Blood Cell Physiology and Storage

Normal RBC Function:

• Oxygen delivery via haemoglobin (1.34 mL O2/g Hb)
• 2,3-DPG modulates oxygen-haemoglobin dissociation
• RBC deformability allows passage through microcirculation
• Normal lifespan 120 days

Storage Lesion [15,16,33]:

During storage at 2-6°C, PRBCs undergo progressive biochemical and structural changes:

Clinical Studies on Blood Age:

• ABLE Trial (2015, PMID: 26771531): Fresh (less than 8 days) vs standard blood in critically ill; no difference in 90-day mortality (37.0% vs 35.3%) [34]
• RECESS Trial (2015, PMID: 25901428): Fresh (less than 10 days) vs older (≥21 days) blood in cardiac surgery; no difference in MODS score [35]
• INFORM Trial (2017, PMID: 28319519): Fresh vs standard issue in hospitalized patients; no difference in mortality [36]

Conclusion: While storage lesion has demonstrable biochemical effects, clinical trials have not shown improved outcomes with fresher blood. Standard blood bank practices (first-in-first-out) are acceptable.

Coagulation Factor Physiology

Fresh Frozen Plasma (FFP) [17,24]:

• Contains all coagulation factors at approximately 1 IU/mL
• Factors V and VIII are most labile (decline to 50-80% by 24h after thawing)
• One mL FFP contains approximately 1 unit of each factor
• Factor levels of 20-30% usually sufficient for haemostasis
• At 10-15 mL/kg, FFP increases factors by approximately 15-25%

Thawed Plasma:

• FFP thawed and stored at 1-6°C for up to 5 days
• Reduced factors V and VIII but adequate for most uses
• Useful for reducing waste and improving availability

Fibrinogen Replacement [18,26]:

• Normal fibrinogen 2-4 g/L
• Critical for clot formation and stability
• First factor to become critically low in dilutional coagulopathy
• Cryoprecipitate: 3 g fibrinogen per 5-unit pool (adult dose)
• Fibrinogen concentrate: 3-4 g (one vial) per adult dose

Platelet Physiology

Normal Platelet Function [7,25]:

• Lifespan 8-10 days
• Adhesion (vWF, GPIb), activation (ADP, thromboxane), aggregation (GPIIb/IIIa)
• Normal count 150-400 × 10^9/L
• Spontaneous bleeding risk increases below 10-20 × 10^9/L

Stored Platelet Changes:

• Must be stored at 20-24°C with continuous agitation (prevents clumping)
• Bacterial contamination risk highest of all blood products (1:3,000)
• 5-7 day shelf life limits stockpiling
• "Platelet storage lesion" includes:
  • Reduced aggregation response
  • Microparticle release
  • Cytokine accumulation
  • pH decline

Platelet Increment Calculation:

• Expected increment = (Platelets transfused × 10^11) / (Blood volume in L × 10^9)
• One apheresis unit should increase count by 30-50 × 10^9/L
• Poor increment suggests alloimmunization, splenomegaly, DIC, sepsis

Transfusion Immunology

ABO Compatibility [12,21]:

• O-negative is "universal donor" for PRBC (lacks A, B antigens)
• AB is "universal donor" for plasma (lacks anti-A, anti-B)
• Rhesus D matching important for D-negative females of childbearing age

Crossmatching Hierarchy [21]:

1. Emergency release (O-negative): No testing; for life-threatening haemorrhage
2. Type-specific uncrossmatched: ABO/Rh matched only; 1-5 minutes
3. Immediate spin/abbreviated crossmatch: Detects ABO incompatibility; 10 minutes
4. Full crossmatch (antiglobulin test): Detects clinically significant antibodies; 45-60 minutes
5. Electronic crossmatch: Computer verification of compatibility; requires two historic ABO/Rh confirmations

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Clinical Indications for Blood Components

Packed Red Blood Cells (PRBC)

Evidence-Based Transfusion Thresholds [3,4,5,37]:

TRICC Trial (Hebert et al., NEJM 1999, PMID: 9971864) [3]:

• Design: RCT, 838 euvolemic critically ill patients
• Intervention: Restrictive (Hb 70-90 g/L) vs liberal (100-120 g/L)
• Primary outcome: 30-day mortality 18.7% vs 23.3% (p=0.11)
• Key findings: Restrictive non-inferior; reduced transfusions by 54%
• Subgroup: APACHE II less than 20 and age less than 55 showed lower mortality with restrictive
• Conclusion: Restrictive threshold safe in most critically ill

TRISS Trial (Holst et al., NEJM 2014, PMID: 25270275) [4]:

• Design: RCT, 998 patients with septic shock
• Intervention: Restrictive (Hb 70 g/L) vs liberal (90 g/L)
• Primary outcome: 90-day mortality 43.0% vs 45.0% (p=0.44)
• Secondary: Ischaemic events similar; fewer transfusions in restrictive
• Conclusion: Restrictive threshold appropriate in septic shock

TRICS-III Trial (Mazer et al., NEJM 2017, PMID: 29116904) [5]:

• Design: RCT, 5,243 patients undergoing cardiac surgery
• Intervention: Restrictive (Hb 75 g/L) vs liberal (95 g/L)
• Primary outcome: Composite (death, MI, stroke, new RRT) 11.4% vs 12.5% (pless than 0.001 for non-inferiority)
• Conclusion: Restrictive strategy non-inferior in cardiac surgery

MINT Trial (Ongoing, PMID: 38497623) [38]:

• Evaluating restrictive vs liberal in acute MI
• Preliminary results (REALITY) suggest possible harm with restrictive in ACS

Fresh Frozen Plasma (FFP)

Indications [6,17,39]:

Important Principles:

• FFP should NOT be used for volume expansion
• FFP should NOT be used to correct elevated INR without bleeding or procedure
• Each unit of FFP increases factors by approximately 3-5%
• Effect is transient (factor half-lives vary from 4-72 hours)
• Risk of TRALI highest with FFP (antibodies in plasma)

Prothrombin Complex Concentrate (PCC) vs FFP for Warfarin Reversal [40,41]:

• PCC provides concentrated factors II, VII, IX, X (4-factor PCC)
• Faster reversal: 15-30 minutes vs hours for FFP
• Lower volume: 25-50 mL vs 1-2 L
• INCH trial (PMID: 23883521): PCC superior to FFP for intracranial haemorrhage + warfarin
• PCC preferred for urgent warfarin reversal; FFP second-line

Platelets

Transfusion Thresholds [7,42,43]:

Platelet Products:

• Pooled platelets: 4-6 donor exposures; approximately 3 × 10^11 platelets
• Apheresis/single donor: One donor; approximately 3 × 10^11 platelets
• Single donor preferred if HLA-matched or multiple transfusions anticipated

Contraindications to Platelet Transfusion:

• TTP/HUS: May worsen microvascular thrombosis (unless life-threatening bleeding)
• HIT: May precipitate thrombosis (use alternative anticoagulation)
• Immune thrombocytopenia (ITP): Rapid destruction; reserve for bleeding

Platelet Dysfunction Despite Normal Count:

• Uraemia (dialysis, DDAVP may help)
• Antiplatelet drugs (aspirin, clopidogrel)
• CPB-related dysfunction
• Hypothermia
• Massive transfusion (dilutional)

Cryoprecipitate

Composition per Unit [18,26]:

• Fibrinogen: 150-250 mg (3 g per 5-unit pool)
• Factor VIII: 80-120 IU
• Factor XIII: 20-30% of plasma level
• von Willebrand factor: Variable
• Fibronectin: Variable

Indications and Dosing [8,18,44]:

CRYOSTAT-2 Trial (Curry et al., Lancet 2023, PMID: 37587580) [8]:

• Early cryoprecipitate (within 45 min) vs standard care in trauma
• Higher proportion achieved fibrinogen >2 g/L (53% vs 26%)
• Trend toward reduced mortality (not statistically significant)
• Supports early empiric fibrinogen replacement in trauma

Fibrinogen Concentrate vs Cryoprecipitate [45]:

• Fibrinogen concentrate: Standardized dose, pathogen-inactivated, faster preparation
• Cryoprecipitate: Lower cost, contains additional factors (FXIII, vWF)
• Both acceptable; choice depends on availability and cost

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Transfusion Complications

Classification of Transfusion Reactions

TRALI (Transfusion-Related Acute Lung Injury)

Definition (ISBT 2019 Consensus) [9,46]:

• New acute lung injury within 6 hours of transfusion
• Hypoxemia (PaO2/FiO2 less than 300 mmHg or SpO2 less than 90% on room air)
• Bilateral infiltrates on CXR
• No evidence of left atrial hypertension (or if present, insufficient to explain pulmonary oedema)
• No pre-existing ALI before transfusion
• Temporal relationship with transfusion

Pathophysiology [9,47]:

• Two-hit hypothesis:
  1. First hit: Patient predisposition (sepsis, surgery, trauma) primes neutrophils
  2. Second hit: Antibodies or bioactive lipids in transfused product activate primed neutrophils
• Donor anti-HLA or anti-HNA antibodies implicated in classic TRALI
• Non-antibody-mediated TRALI from bioactive lipids in stored products

Risk Factors:

• High-plasma-volume products (FFP > platelets > PRBC)
• Female donors (multiparous women have anti-HLA antibodies)
• Older blood products
• Patient factors: sepsis, mechanical ventilation, shock

Incidence: 1:5,000 to 1:10,000 transfusions (reduced by male-only plasma policies)

Mitigation Strategies:

• Male-only plasma policies (Australian Red Cross Lifeblood)
• Screening of female donors for HLA antibodies
• Leukoreduction of cellular products

Management:

• Stop transfusion immediately
• Supportive care (oxygen, mechanical ventilation if needed)
• Lung-protective ventilation if intubated
• Diuretics NOT indicated (non-cardiogenic)
• Steroids NOT proven beneficial
• Most resolve within 48-72 hours
• Mortality 5-10%

TACO (Transfusion-Associated Circulatory Overload)

Definition (ISBT 2019) [10,48]:

• New or worsening respiratory distress within 12 hours of transfusion
• Evidence of fluid overload:
  • Acute pulmonary oedema
  • Elevated BNP/NT-proBNP
  • Positive fluid balance
  • Evidence of left heart failure

Pathophysiology:

• Volume overload from transfused blood products
• Exceeds cardiac capacity
• Hydrostatic pulmonary oedema

Risk Factors:

• Elderly (>70 years)
• Pre-existing cardiac disease
• Renal impairment
• Rapid transfusion rate
• Large transfusion volume
• Positive fluid balance

Incidence: 1:100 to 1:700 transfusions (underreported)

TRALI vs TACO Differentiation [19,49]:

Diagnostic Workup:

• BNP or NT-proBNP (best discriminator)
• Echocardiography
• Fluid balance assessment
• CXR comparison (pre and post)

Management:

• Stop or slow transfusion
• Diuretics (furosemide 40-80 mg IV)
• Oxygen therapy
• Sit upright
• Consider NIV
• Restrict further fluids
• Mortality 5-15%

Acute Haemolytic Transfusion Reaction

Pathophysiology [12,50]:

• ABO incompatibility (usually clerical error)
• Recipient antibodies destroy transfused RBCs
• Complement activation
• Intravascular haemolysis
• DIC, shock, acute kidney injury

Clinical Features:

• Fever, rigors (may be first sign under anaesthesia)
• Hypotension
• Haemoglobinuria (red/brown urine)
• Flank pain
• DIC (bleeding)
• Acute kidney injury

Incidence: 1:25,000 to 1:40,000 (largely preventable)

Management:

• STOP transfusion immediately
• Maintain IV access (new line)
• Send blood and transfused unit to blood bank
• Aggressive fluid resuscitation (maintain UO >1 mL/kg/h)
• Monitor for DIC
• Treat hyperkalaemia
• Dialysis if severe AKI

Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

Definition: Temperature rise ≥1°C during or within 4 hours of transfusion, without other cause [11,51]

Pathophysiology:

• Cytokines accumulated in stored products (IL-1, IL-6, TNF-α)
• Recipient antibodies to donor leukocytes

Incidence: Most common reaction; 0.1-1% with leukoreduction

Management:

• Slow or stop transfusion
• Rule out haemolytic reaction
• Paracetamol for comfort
• Can often resume if haemolytic excluded
• Leukoreduction prevents most FNHTR

Allergic and Anaphylactic Reactions

Allergic Reaction [52]:

• Urticaria, pruritus, flushing
• Usually mild; 1-3% of transfusions
• Caused by reaction to plasma proteins
• Management: antihistamines, may continue transfusion slowly

Anaphylaxis [52]:

• Severe hypotension, bronchospasm, angioedema
• Rare: 1:20,000 to 1:50,000
• Associated with IgA deficiency and anti-IgA antibodies
• Management: stop transfusion, adrenaline, resuscitation
• Future transfusions: washed products, IgA-deficient donors

Hyperkalaemia

Mechanism [53]:

• Potassium leaks from stored RBCs during storage
• K+ concentration may reach 50 mmol/L by Day 42
• Rapid infusion delivers significant potassium load

Risk Factors:

• Rapid transfusion (>1 unit in 5 min)
• Renal failure
• Neonates
• Massive transfusion
• Older blood

Prevention:

• Use fresher blood if available for high-risk patients
• Wash PRBCs (removes supernatant K+)
• Monitor K+ frequently during massive transfusion
• Rapid infuser devices with warming

Management:

• Standard hyperkalaemia treatment
• Calcium gluconate for cardiac protection
• Insulin/glucose
• Consider dialysis

Hypocalcaemia (Citrate Toxicity)

Mechanism [54]:

• Citrate anticoagulant in blood products chelates ionized calcium
• FFP has more citrate than PRBCs
• Citrate normally metabolized by liver
• Shocked, hypothermic, or liver failure patients cannot metabolize citrate

Clinical Features:

• Perioral tingling, paraesthesias
• Muscle cramps, tetany
• Hypotension
• Prolonged QT, arrhythmias
• Reduced myocardial contractility

Management:

• Monitor ionized calcium during massive transfusion
• Calcium gluconate 1 g IV per 4 units transfused (or per 10 mL/kg FFP)
• Target iCa2+ >1.1 mmol/L

Infectious Complications

Current Risk in Australia (per unit transfused) [55]:

Screening includes NAT testing for HIV, HCV, HBV. Bacterial contamination remains highest risk, particularly for platelets (room temperature storage).

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Massive Transfusion and Damage Control Resuscitation

PROPPR Trial (Holcomb et al., JAMA 2015, PMID: 25647203)

Design: Pragmatic RCT, 680 patients with severe trauma and major bleeding [20]

Intervention:

• 1:1:1 ratio (FFP:platelets:PRBC)
• 1:1:2 ratio (FFP:platelets:PRBC)

Primary Outcome: 24-hour and 30-day mortality similar

Secondary Outcomes:

• More patients achieved haemostasis in 1:1:1 group (86% vs 78%)
• Death from exsanguination at 24 hours: 9.2% vs 14.6% (p=0.006)
• No difference in complications

Conclusion: 1:1:1 ratio preferred; reduces early death from exsanguination

Damage Control Resuscitation Principles

Components [56,57]:

1. Permissive hypotension: Target SBP 80-90 mmHg until surgical control

   • Contraindicated in TBI, spinal cord injury
   • Avoid over-resuscitation with crystalloid

2. Haemostatic resuscitation: Blood products over crystalloid

   • 1:1:1 ratio FFP:platelets:PRBC
   • Early empiric fibrinogen replacement

3. Damage control surgery: Abbreviated surgery for bleeding control

   • Packing, temporary closure
   • Definitive repair after resuscitation

4. Correction of lethal diamond:

   • Temperature >35°C (blood warmers)
   • pH correction (treat cause, not bicarbonate)
   • Coagulopathy correction (blood products)
   • Calcium replacement (iCa2+ >1.1 mmol/L)

5. TXA within 3 hours: CRASH-2 evidence [58]

   • 1 g IV load over 10 minutes + 1 g over 8 hours
   • Harm if given >3 hours post-injury

Viscoelastic Testing (TEG/ROTEM)

Role in Massive Transfusion [59,60]:

• Point-of-care assessment of clot formation and lysis
• Faster than conventional coagulation tests
• Guides goal-directed transfusion
• Reduces overall blood product usage by 20-30%

Key Parameters (ROTEM):

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Australian Blood Service and Compatibility Testing

Australian Red Cross Lifeblood

Overview [13]:

• Sole supplier of blood and blood products in Australia
• Collects approximately 1.3 million donations annually
• Provides PRBC, FFP, platelets, cryoprecipitate, plasma derivatives
• Patient Blood Management programs reduce unnecessary transfusion

Product Availability:

• PRBC: Widely available; some remote areas have limited stocks
• FFP: Available frozen; requires thawing (30-45 min)
• Platelets: Limited shelf life (5-7 days); may require special ordering
• Cryoprecipitate: Available frozen

Emergency Blood:

• All hospitals should stock O-negative PRBC for emergencies
• Remote facilities may have limited O-negative supply
• Aeromedical retrieval may carry O-negative blood

Pre-Transfusion Testing

Group and Screen/Crossmatch [21]:

1. ABO and Rh typing: Forward and reverse grouping
2. Antibody screen: Detects clinically significant antibodies
3. Crossmatch: Confirms compatibility between donor and recipient

Validity Periods:

• Group and screen: Valid 72 hours (if no transfusion or pregnancy in 3 months)
• Crossmatch: Specific to that unit

Electronic Crossmatch [61]:

• Computer verification of compatibility
• Requires two historic ABO/Rh confirmations
• Suitable for patients with negative antibody screen
• Reduces workload, faster availability

Sample Requirements:

• Positive patient identification
• Labelled at bedside
• Reject if discrepancies

Emergency Blood Protocols

Massive Haemorrhage Protocol [62]:

1. Activation criteria (clinical or scoring: ABC, TASH)
2. Immediate release of O-negative PRBC (or type-specific if known)
3. Transfusion packs with balanced ratios
4. Communication pathway with blood bank
5. Goal-directed adjustment with POC testing

O-Negative Usage:

• Reserve for genuine emergencies
• Switch to type-specific as soon as group confirmed
• Male patients can receive O-positive if O-negative limited
• Rh-negative females of childbearing age should receive O-negative

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Special Populations and Considerations

Cardiac Surgery

TRICS-III Implications [5]:

• Restrictive threshold (Hb 75 g/L) non-inferior to liberal (95 g/L)
• Reduces transfusion exposure
• Some surgeons still use higher thresholds for complex cases

Platelet Dysfunction Post-CPB [63]:

• CPB causes platelet activation and degranulation
• Platelet count may be adequate but function impaired
• Consider platelet transfusion despite "normal" count if bleeding
• DDAVP may improve platelet function

Sepsis and Septic Shock

TRISS Trial Implications [4]:

• Restrictive (Hb 70 g/L) appropriate in septic shock
• No increase in ischaemic events
• Consider higher threshold if evidence of tissue hypoxia (lactate, ScvO2)

Coagulopathy in Sepsis:

• FFP/cryoprecipitate for DIC with bleeding
• Platelets for thrombocytopenia with bleeding
• Vitamin K for prolonged INR

Chronic Kidney Disease

Transfusion Considerations [64]:

• Avoid transfusion if possible (alloimmunization, iron overload)
• Transfusion sensitizes for renal transplant
• Erythropoiesis-stimulating agents preferred
• If transfusion needed, use restrictive threshold
• Consider leukoreduced, CMV-negative products

Uraemic Platelet Dysfunction:

• Platelet count often normal
• Platelet function impaired
• DDAVP (0.3 mcg/kg IV) may improve function
• Dialysis improves platelet function
• Platelet transfusion less effective due to uraemic milieu

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples [14,22,65]:

Clinical Considerations:

• Higher rates of chronic diseases requiring transfusion:
  • End-stage renal disease (10-20× prevalence)
  • Rheumatic heart disease
  • Liver disease
  • GI bleeding
  • Trauma
• May have rare blood group phenotypes requiring special matching
• Iron deficiency common; address underlying cause

Healthcare Access:

• Geographic isolation in remote communities
• Limited blood product availability in remote areas
• Retrieval to tertiary centres may be required for massive transfusion
• RFDS carries limited blood products; coordinate with blood bank

Cultural Considerations:

• Blood transfusion generally acceptable but discuss with patient/family
• Some traditional beliefs about blood and body integrity
• Involve Aboriginal Health Workers and Liaison Officers
• Allow time for family discussion and decision-making
• Respect for Elders in decision-making
• Language barriers; use interpreters

Māori Health (New Zealand):

• Higher rates of chronic disease
• Whānau (family) involvement in decisions
• Tikanga (cultural protocols) considerations
• Māori Health Workers for cultural support

Jehovah's Witnesses

Blood Product Refusal [66]:

• PRBC, FFP, platelets, whole blood generally refused
• Individual variation in acceptance of components
• Some accept albumin, immunoglobulins, factor concentrates
• Always clarify with individual patient

Management Strategies:

• Preoperative optimization (iron, erythropoietin)
• Intraoperative cell salvage (often accepted)
• Acute normovolaemic haemodilution
• Minimize blood loss (surgical technique, antifibrinolytics)
• Accept lower Hb thresholds

Legal and Ethical:

• Competent adult has right to refuse
• Document discussion thoroughly
• Advance directive/healthcare directive if available
• Different considerations for children (court order may be sought)

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SAQ Practice Questions

SAQ 1: Transfusion Thresholds and Component Therapy

Time Allocation: 10 minutes Total Marks: 20

Stem: A 68-year-old male is Day 2 post-emergency laparotomy for perforated diverticulitis with faecal peritonitis. He remains ventilated in ICU on noradrenaline 0.15 mcg/kg/min. He is noted to be oozing from his laparotomy wound and drain sites.

Observations:

• HR: 105 bpm
• BP: 95/60 mmHg (MAP 72)
• Temperature: 38.2°C
• SpO2: 94% on FiO2 0.4

Laboratory Results:

• Hb: 72 g/L
• Platelets: 65 × 10^9/L
• INR: 1.8
• APTT: 48 seconds
• Fibrinogen: 1.2 g/L
• Lactate: 3.8 mmol/L

Questions:

1.1 Outline the evidence for transfusion thresholds in critically ill patients and apply this to the decision to transfuse PRBCs in this patient. (8 marks)

1.2 Discuss your approach to correcting this patient's coagulopathy, including specific blood products, dosing, and targets. (8 marks)

1.3 List four complications of blood component therapy you would anticipate and how you would prevent or manage each. (4 marks)

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Model Answer

Question 1.1 (8 marks)

Evidence for Transfusion Thresholds (4 marks):

Landmark Trials:

• TRICC Trial (Hebert 1999, PMID 9971864): Restrictive (Hb 70-90 g/L) vs liberal (100-120 g/L) in 838 critically ill patients. No mortality difference (18.7% vs 23.3%); 54% reduction in transfusions with restrictive strategy. Supports Hb less than 70 g/L threshold in general ICU. (1 mark)

• TRISS Trial (Holst 2014, PMID 25270275): 998 patients with septic shock. Restrictive (Hb 70 g/L) non-inferior to liberal (90 g/L); 90-day mortality 43% vs 45%. Restrictive safe in septic shock. (1 mark)

• TRICS-III (Mazer 2017, PMID 29116904): Cardiac surgery patients. Restrictive (Hb 75 g/L) non-inferior to liberal. (0.5 marks)

• Meta-analyses: Carson meta-analysis (PMID 27049757) confirms restrictive transfusion reduces mortality and doesn't increase morbidity. (0.5 marks)

Application to This Patient (4 marks):

This patient has:

• Septic shock (peritonitis, vasopressor requirement) - TRISS supports restrictive threshold (Hb 70) (1 mark)
• Active oozing/bleeding - may require higher threshold to support haemostasis (1 mark)
• Tissue hypoperfusion (lactate 3.8) - subgroup analyses suggest caution at very low Hb (1 mark)

Decision: Hb 72 g/L is at threshold. Given active bleeding and elevated lactate, would transfuse 1-2 units PRBC targeting Hb 80-90 g/L while addressing coagulopathy and source of bleeding. (1 mark)

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Question 1.2 (8 marks)

Coagulopathy Assessment (2 marks):

• INR 1.8 (elevated) - factor deficiency
• APTT 48 (mildly elevated) - intrinsic pathway
• Platelets 65 (low, threshold 50 for procedures/20 for sepsis)
• Fibrinogen 1.2 g/L (low, target >1.5-2.0 g/L)
• Context: Sepsis-associated DIC vs consumptive coagulopathy vs dilutional

Blood Product Therapy (6 marks):

Monitoring: Repeat coagulation studies 15-30 min post-transfusion; consider viscoelastic testing (TEG/ROTEM) if available for goal-directed therapy. (0.5 marks)

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Question 1.3 (4 marks) - 1 mark each for complication + prevention/management

1. TACO: Risk with multiple products in septic patient with positive fluid balance

   • Prevention: Transfuse slowly, consider furosemide between units, monitor JVP/respiratory status

2. TRALI: Risk with FFP (plasma-containing products)

   • Recognition: New hypoxia within 6h, bilateral infiltrates, low BNP
   • Management: Stop transfusion, supportive care, lung-protective ventilation

3. Hypocalcaemia: Citrate toxicity with FFP and PRBC

   • Prevention: Monitor iCa2+, give calcium gluconate 1 g per 4 units
   • Target iCa2+ >1.1 mmol/L

4. Hyperkalaemia: Potassium leak from stored PRBC

   • Prevention: Monitor K+, consider fresher units if high-risk
   • Management: Standard hyperkalaemia treatment, calcium for cardiac protection

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SAQ 2: TRALI vs TACO Differentiation

Time Allocation: 10 minutes Total Marks: 20

Stem: A 75-year-old female with chronic kidney disease stage 4 and ischaemic cardiomyopathy (LVEF 35%) was admitted with hospital-acquired pneumonia and received 2 units of PRBC for Hb 68 g/L. Four hours into the second unit, she develops acute dyspnoea and hypoxia.

Observations:

• HR: 110 bpm
• BP: 165/95 mmHg
• RR: 32/min
• SpO2: 82% on 15L O2 via non-rebreather
• Temperature: 37.8°C

CXR: Bilateral alveolar infiltrates with cardiomegaly

Questions:

2.1 Outline the differential diagnosis for acute respiratory deterioration post-transfusion and the key clinical and investigative features that differentiate TRALI from TACO. (10 marks)

2.2 Describe your initial management of this patient. (6 marks)

2.3 Discuss the reporting requirements and preventive strategies for transfusion-related pulmonary complications. (4 marks)

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Model Answer

Question 2.1 (10 marks)

Differential Diagnosis (3 marks):

1. TACO (Transfusion-Associated Circulatory Overload)
2. TRALI (Transfusion-Related Acute Lung Injury)
3. Allergic/anaphylactic reaction
4. Bacterial contamination/septic transfusion reaction
5. Haemolytic transfusion reaction with pulmonary effects
6. Underlying pneumonia progression
7. Pulmonary embolism
8. Acute coronary syndrome with pulmonary oedema

TRALI vs TACO Differentiation (7 marks):

This Patient: High risk for TACO given age, CKD, cardiomyopathy, hypertension, cardiomegaly on CXR. Send BNP urgently.

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Question 2.2 (6 marks)

Immediate Management:

1. STOP transfusion immediately - return blood to blood bank with request for investigation (1 mark)

2. Airway and Breathing (2 marks):

   • High-flow oxygen or NIV (CPAP/BiPAP) if tolerated
   • Prepare for intubation if deteriorating
   • Sit patient upright

3. Circulation (2 marks):

   • IV access (new line if possible)
   • Trial of diuretics: Furosemide 40-80 mg IV (diagnostic and therapeutic for TACO)
   • If no response, consider TRALI and supportive management
   • Avoid further fluids

4. Investigations (1 mark):

   • BNP/NT-proBNP (urgent)
   • ABG
   • ECG
   • Echocardiography
   • Repeat CXR

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Question 2.3 (4 marks)

Reporting Requirements (2 marks):

• Report to blood bank immediately (triggers investigation)
• Notify Australian Red Cross Lifeblood via STIR (Serious Transfusion Incident Reporting)
• Complete hospital transfusion reaction form
• Document in medical record
• Consider reporting to TGA (therapeutic goods adverse event)

Prevention Strategies (2 marks):

For TRALI:

• Male-only plasma policies (Australian Lifeblood practice)
• HLA antibody screening of female donors
• Leukoreduction of cellular products
• Use only essential transfusions

For TACO:

• Restrictive transfusion thresholds
• Slow transfusion rate (3-4 hours per unit in high-risk patients)
• Single-unit transfusion policy with reassessment
• Diuretic cover in high-risk patients
• Careful fluid balance monitoring

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Hot Case Scenarios

Hot Case 1: Post-Cardiac Surgery Coagulopathy

Setting: ICU Bed 8, Cardiac ICU Duration: 20 minutes (10 min assessment + 10 min discussion)

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Actor/Simulator Briefing (Not given to candidate):

Patient Details:

• Age: 72 years
• Gender: Male
• Admission diagnosis: Post-CABG × 4 (6 hours ago)
• Day of ICU stay: Day 0 (immediate post-op)

History:

• CABG for severe triple vessel disease, LVEF 45%
• CPB time 140 minutes, cross-clamp 95 minutes
• PMH: Hypertension, diabetes, aspirin/clopidogrel (held 7 days pre-op)
• Intra-op: 4 units PRBC, 2 units FFP, significant oozing at closure

Examination Findings:

• General: Sedated, intubated, cool peripheries
• Airway: 8.0 ETT, well-positioned
• Breathing: Bilateral air entry, minimal ventilator support (PS 10, PEEP 5, FiO2 0.4)
• Circulation: HR 88 (paced), BP 105/60 on noradrenaline 0.08 mcg/kg/min
  • "Mediastinal drains: 400 mL in 2 hours (200 mL/hr)"
  • Pacing wires in situ
  • PA catheter showing CI 2.1, CVP 12
• Disability: RASS -4 (propofol/fentanyl)
• Exposure: Temp 35.8°C

Charts/Data Available:

• Chest drain output: 150 mL (hour 1), 250 mL (hour 2) - total 400 mL/2h
• Hb: 78 g/L (down from 85 at arrival)
• Platelets: 72 × 10^9/L
• INR: 1.6, APTT: 52s
• Fibrinogen: 1.1 g/L
• TEG: Prolonged R-time, reduced MA, no fibrinolysis

Current Management:

• Ventilator: SIMV + PS, FiO2 0.4, PEEP 5
• Noradrenaline 0.08 mcg/kg/min
• Propofol 20 mL/hr, fentanyl 50 mcg/hr
• Active rewarming with Bair Hugger

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Expected Performance:

Key Findings to Identify:

1. Excessive mediastinal drain output (>200 mL/hr = re-exploration threshold)
2. Dropping Hb, thrombocytopenia, coagulopathy
3. Hypothermia (borderline)
4. CPB-related platelet dysfunction

Management Priorities:

1. Immediate surgical consultation regarding re-exploration
2. Active rewarming (target >36°C)
3. Blood product replacement:
   • PRBC to maintain Hb 80-90 g/L
   • Platelets (CPB dysfunction + low count)
   • Cryoprecipitate for fibrinogen less than 1.5 g/L
   • FFP for INR >1.5
4. Calcium replacement (check ionized calcium)
5. Consider protamine if residual heparin (ACT/anti-Xa)
6. TXA if ongoing bleeding

Discussion Points:

• Surgical vs medical bleeding distinction
• TEG/ROTEM interpretation and goal-directed therapy
• TRICS-III evidence for transfusion threshold
• CPB effects on haemostasis
• Re-exploration decision criteria

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Hot Case 2: Septic Shock with DIC

Setting: ICU Bed 3, General ICU Duration: 20 minutes

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Actor/Simulator Briefing:

Patient Details:

• Age: 58 years
• Gender: Female
• Admission diagnosis: Necrotizing fasciitis, post-debridement
• Day of ICU stay: Day 3

History:

• Admitted with necrotizing fasciitis of left thigh
• Emergency fasciotomy and debridement Day 0
• Returned to theatre Day 2 for further debridement
• Blood cultures: Group A Streptococcus
• On meropenem + clindamycin + IVIG

Examination Findings:

• General: Febrile, agitated despite sedation
• Airway: 7.5 ETT
• Breathing: Bilateral crackles, FiO2 0.6, PEEP 10
• Circulation: HR 125, BP 85/50 on noradrenaline 0.3, vasopressin 0.03
  • Warm peripheries (distributive shock)
  • Oozing from all IV sites and wound
• Disability: RASS -1 (attempting to pull at lines)
• Exposure: Temp 39.2°C, extensive thigh wound with VAC dressing

Laboratory Results:

• Hb: 65 g/L
• WCC: 2.4 × 10^9/L
• Platelets: 28 × 10^9/L
• INR: 2.4, APTT: 65s
• Fibrinogen: 0.8 g/L
• D-dimer: >20,000
• Lactate: 6.2 mmol/L
• Creatinine: 280 μmol/L

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Expected Performance:

Key Findings:

1. DIC (elevated INR/APTT, low platelets, low fibrinogen, high D-dimer)
2. Overt DIC with bleeding (oozing from sites)
3. Severe septic shock (high vasopressor requirements)
4. Multi-organ dysfunction (renal, haematological)

Management:

1. Blood product therapy:
   • PRBC 2 units (Hb 65 in bleeding patient - transfuse despite TRISS)
   • FFP 15-20 mL/kg for INR 2.4 with bleeding
   • Cryoprecipitate 10 units for fibrinogen 0.8 g/L
   • Platelets 1 adult dose for plt 28 with bleeding
2. Continue source control (surgical review)
3. Antibiotics + IVIG
4. Consider rFVIIa only as last resort (risk of thrombosis in DIC)
5. Supportive care for MODS

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Viva Scenarios

Viva 1: Evidence-Based Transfusion Practice

Stem: "A 65-year-old man in your ICU with pneumonia and respiratory failure has a haemoglobin of 74 g/L. The junior registrar asks whether he should be transfused. Discuss."

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Examiner Opening Question: "What are the key considerations in deciding whether to transfuse this patient?"

Expected Answer:

• Consider symptoms of anaemia (tachycardia, dyspnoea - may be confounded by pneumonia)
• Consider oxygen delivery equation (DO2 = CO × CaO2)
• Review evidence for transfusion thresholds in ICU
• Apply restrictive vs liberal strategy
• Individual patient factors (cardiac disease, ongoing bleeding)

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Follow-up 1: "Tell me about the TRICC trial."

Expected Answer:

• Citation: Hebert et al., NEJM 1999, PMID 9971864
• Design: RCT, 838 euvolemic critically ill patients
• Intervention: Restrictive (Hb 70-90 g/L) vs liberal (100-120 g/L)
• Primary outcome: 30-day mortality 18.7% vs 23.3% (p=0.11, not significant)
• Key findings: Restrictive strategy reduced transfusions by 54% without harm
• Subgroup: Younger (less than 55) and less sick (APACHE less than 20) may have benefited from restrictive
• Limitations: Excluded active bleeding, chronic anaemia, cardiac surgery
• Conclusion: Restrictive threshold (70 g/L) is safe in most critically ill

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Follow-up 2: "What about in septic shock specifically?"

Expected Answer:

• TRISS Trial: Holst et al., NEJM 2014, PMID 25270275
• 998 patients with septic shock
• Restrictive (Hb 70 g/L) vs liberal (90 g/L)
• 90-day mortality 43.0% vs 45.0% (not significant)
• No difference in ischaemic events, RRT, or ICU LOS
• Restrictive strategy reduced transfusion by 50%
• Conclusion: Restrictive threshold appropriate in septic shock

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Follow-up 3: "The patient also has severe aortic stenosis. Does this change your approach?"

Expected Answer:

• Severe AS is a concern - fixed cardiac output state
• Limited ability to increase CO to compensate for anaemia
• TRICC excluded this population
• May consider higher threshold (Hb 80-90 g/L)
• Consider symptoms and signs of tissue hypoxia (lactate, ScvO2)
• Balance transfusion risks against hypoxia risk
• Individualized approach; no specific trial evidence

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Follow-up 4: "What about in acute coronary syndrome?"

Expected Answer:

• Controversial area with conflicting evidence
• REALITY Trial (2024, PMID 38497623): Suggested possible harm with restrictive strategy in ACS
• MINT Trial: Ongoing
• Current approach: May use higher threshold (80-100 g/L) in active ischaemia
• Hb supports oxygen delivery to ischaemic myocardium
• Transfusion also has risks (volume, immunomodulation)
• Consider symptoms and ECG changes
• Most would transfuse for Hb less than 80 g/L with active ischaemia

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Viva 2: TRALI and TACO

Stem: "A nurse calls you urgently because a patient receiving his third unit of PRBC for GI bleeding has suddenly become acutely short of breath. SpO2 is 78% on room air. Discuss your approach."

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Examiner Opening Question: "What are your immediate priorities?"

Expected Answer:

1. Stop the transfusion immediately
2. Assess and stabilize:
   • A: Check airway patency
   • B: Apply high-flow oxygen, assess work of breathing
   • C: Check BP, HR, establish/confirm IV access
3. Immediate differential:
   • TRALI
   • TACO
   • Anaphylaxis
   • Haemolytic reaction
   • Bacterial contamination
   • Underlying condition (PE, aspiration)
4. Notify blood bank - retain blood product for investigation

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Follow-up 1: "The BP is 160/100, JVP is elevated, and there are bilateral crackles. What do you think is happening?"

Expected Answer:

• High suspicion for TACO (Transfusion-Associated Circulatory Overload)
• Features supporting TACO:
  • Hypertension (not hypotension)
  • Elevated JVP
  • Pulmonary oedema
  • Third unit of blood (volume load)
  • GI bleeding patient may have underlying cardiac disease

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Follow-up 2: "How would you differentiate TRALI from TACO?"

Expected Answer:

• Key discriminator: BNP/NT-proBNP
  • "TRALI: Normal or low"
  • "TACO: Elevated (>1.5× baseline)"
• Other features:
  • "Fluid balance: TRALI neutral/negative; TACO positive"
  • "BP: TRALI often hypotensive; TACO often hypertensive"
  • "JVP: TRALI normal; TACO elevated"
  • "CXR: TRALI ARDS pattern; TACO cardiogenic (cardiomegaly, effusions)"
  • "Response to diuretics: TRALI no; TACO yes"
  • "Echocardiography: TRALI normal; TACO elevated filling pressures"

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Follow-up 3: "How would you manage confirmed TACO?"

Expected Answer:

• Immediate:
  • Stop transfusion
  • Oxygen, sit upright
  • IV furosemide 40-80 mg (diagnostic and therapeutic)
  • NIV (CPAP/BiPAP) if needed
  • Prepare for intubation if deteriorating
• Subsequent:
  • Aim negative fluid balance
  • Review need for further transfusion
  • "If further transfusion needed:"
    • Transfuse slowly (3-4 hours per unit)
    • Single unit then reassess
    • Diuretic cover
    • Consider concentrated products
  • Report to blood bank
  • Complete adverse event documentation

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Follow-up 4: "What are the prevention strategies for TRALI?"

Expected Answer:

• Australian Lifeblood measures:
  • Male-only plasma (FFP, cryoprecipitate)
  • Female donor HLA antibody screening
  • Leukoreduction of cellular products
• Clinical measures:
  • Transfuse only when indicated (restrictive strategy)
  • Avoid unnecessary FFP (highest TRALI risk)
  • Document and investigate all reactions
• Pathophysiology-based:
  • TRALI is antibody-mediated (donor anti-HLA/HNA)
  • Multiparous women have highest antibody rates
  • Leukoreduction reduces cytokine-mediated reactions

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Viva 3: Massive Transfusion and Blood Component Ratios

Stem: "A 28-year-old male is brought to ED following a motorcycle accident with a traumatic amputation of his left leg. He is in haemorrhagic shock. Discuss your approach to blood product therapy."

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Examiner Opening Question: "What is massive transfusion and when would you activate the protocol?"

Expected Answer:

• Definitions of massive transfusion:

  • 10 units PRBC in 24 hours

  • 4 units PRBC in 1 hour with ongoing bleeding

  • 50% blood volume replaced in 3 hours

• Activation criteria (use validated scores):
  • "ABC Score: Penetrating mechanism, SBP ≤90, HR ≥120, positive FAST (≥2 = activate)"
  • "TASH Score: >16 points = 50% probability of massive transfusion"
  • Clinical judgement in obvious exsanguinating haemorrhage

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Follow-up 1: "Tell me about the optimal ratio of blood products."

Expected Answer:

• PROPPR Trial (Holcomb et al., JAMA 2015, PMID 25647203):
  • 680 trauma patients with major bleeding
  • 1:1:1 (FFP:platelets:PRBC) vs 1:1:2
  • No difference in 24-hour or 30-day mortality
  • "Key finding: Death from exsanguination at 24h significantly lower with 1:1:1 (9.2% vs 14.6%, p=0.006)"
  • "More patients achieved haemostasis with 1:1:1 (86% vs 78%)"
• Current practice: 1:1:1 ratio is standard for massive transfusion
• Rationale: Approximates whole blood; prevents dilutional coagulopathy

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Follow-up 2: "What about fibrinogen replacement?"

Expected Answer:

• Fibrinogen is the first factor to become critically low in massive haemorrhage
• Target: >1.5 g/L (some suggest >2 g/L in trauma)
• CRYOSTAT-2 Trial (Curry et al., Lancet 2023, PMID 37587580):
  • Early empiric cryoprecipitate (within 45 min) vs standard care
  • More patients achieved fibrinogen >2 g/L (53% vs 26%)
  • Trend toward mortality benefit (not significant)
• Dosing: 10 units cryoprecipitate (2 pools) provides approximately 3 g fibrinogen
• Alternative: Fibrinogen concentrate (pathogen-inactivated, standardized dose)

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Follow-up 3: "Discuss the role of tranexamic acid."

Expected Answer:

• CRASH-2 Trial (Shakur et al., Lancet 2010, PMID 20554319):
  • 20,211 trauma patients with significant haemorrhage
  • TXA (1 g load + 1 g over 8h) vs placebo
  • "Mortality reduction: 14.5% vs 16.0% (p=0.0035)"
  • "Critical timing: Benefit only if given less than 3 hours from injury"
  • "After 3 hours: Increased mortality from bleeding"
• Current practice: TXA 1 g IV load over 10 min + 1 g over 8 hours
• Give as early as possible; do NOT delay
• Also supported in PPH (WOMAN trial), surgery (ATACAS)

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Follow-up 4: "What complications would you anticipate during massive transfusion?"

Expected Answer:

• Lethal Diamond (extend from lethal triad):
  1. Hypothermia: Use blood warmers, all fluids warmed, target >35°C
  2. Acidosis: Treat cause (restore perfusion), not bicarbonate
  3. Coagulopathy: Blood products as discussed
  4. Hypocalcaemia: Citrate toxicity; give calcium gluconate 1 g per 4 units; target iCa2+ >1.1
• Hyperkalaemia: Monitor K+, treat as needed
• TACO: Risk with large volumes; monitor respiratory status
• TRALI: Less common but possible with plasma products
• Acute haemolytic reaction: Usually ABO incompatibility (clerical error)
• Transfusion-related immunomodulation: Possible increased infection risk

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Viva 4: Platelet Transfusion

Stem: "A 62-year-old woman with AML is Day 10 post-induction chemotherapy. Her platelet count is 8 × 10^9/L and she is clinically well. Discuss platelet transfusion."

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Examiner Opening Question: "What are the thresholds for prophylactic platelet transfusion?"

Expected Answer:

• 10 × 10^9/L: Standard prophylactic threshold in stable patients
• 20 × 10^9/L: Fever, sepsis, DIC, minor bleeding
• 50 × 10^9/L: Minor invasive procedures (CVC, LP, minor surgery)
• 100 × 10^9/L: Neurosurgery, eye surgery, intracranial bleeding
• Evidence base:
  • "Slichter and colleagues: 10 × 10^9/L threshold reduces platelet usage without increasing bleeding"
  • Higher thresholds in presence of risk factors for bleeding

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Follow-up 1: "She develops a temperature of 38.5°C. Does this change your approach?"

Expected Answer:

• Fever increases platelet consumption and bleeding risk
• Would increase threshold to 20 × 10^9/L
• Current platelet count (8) below this threshold
• Would transfuse one adult dose of platelets
• Also investigate fever source (febrile neutropenia workup)

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Follow-up 2: "Tell me about platelet refractoriness."

Expected Answer:

• Definition: Failure to achieve expected platelet increment
• Expected increment: 30-50 × 10^9/L per apheresis unit
• Causes:
  • "Immune: HLA alloimmunization (most common), ABO incompatibility"
  • "Non-immune: Sepsis, DIC, splenomegaly, medications"
• Investigation:
  • Calculate corrected count increment (CCI)
  • HLA antibody testing
  • Trial of ABO-matched, fresh platelets
• Management:
  • Treat underlying cause if non-immune
  • HLA-matched platelets if alloimmunized
  • Consider crossmatched platelets
  • Antifibrinolytics (TXA) to reduce bleeding

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Follow-up 3: "When should you NOT transfuse platelets?"

Expected Answer:

• TTP/HUS: May worsen microvascular thrombosis
  • "Exception: Life-threatening bleeding"
• HIT (Type 2): May precipitate thrombosis
  • Use alternative anticoagulation
  • Can transfuse once anticoagulation established if bleeding
• ITP: Rapid destruction; transfused platelets have short survival
  • Reserve for life-threatening bleeding
  • IVIG may improve survival of transfused platelets
• Drug-induced thrombocytopenia: Depends on mechanism

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Viva 5: Indigenous Health and Blood Transfusion

Stem: "An Aboriginal man from a remote community in the Northern Territory is admitted to your ICU with severe GI bleeding from oesophageal varices. He requires blood transfusion. Discuss the specific considerations."

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Examiner Opening Question: "What are the specific healthcare challenges for this patient?"

Expected Answer:

• Geographic isolation: Remote community, limited blood product availability
• Healthcare access: May have delayed presentation, limited baseline investigations
• Higher disease burden: Aboriginal people have higher rates of:
  • Chronic liver disease
  • Chronic kidney disease
  • Diabetes, cardiovascular disease
• Potential for rare blood group phenotypes: May require special matching
• Cultural considerations: Blood transfusion acceptability, family involvement
• Communication: May have English as second/third language

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Follow-up 1: "How would you approach informed consent?"

Expected Answer:

• Language: Use professional interpreter (not family member for medical discussion)
• Aboriginal Health Worker/Liaison Officer: Involve early
• Family involvement: Extended family may need to be involved in decisions
  • Ask patient who they want present
  • Respect role of Elders
• Culturally appropriate communication:
  • Allow time for questions
  • Use simple language
  • Check understanding
  • Avoid confrontational direct questions
• Blood transfusion specifically:
  • Generally acceptable, but confirm with patient
  • Some traditional beliefs about blood
  • Explain benefits and risks
  • Document discussion

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Follow-up 2: "What are the logistical challenges for blood product supply?"

Expected Answer:

• Limited stock in remote areas: May only have O-negative available
• RFDS (Royal Flying Doctor Service): May need to arrange blood product retrieval
• Interstate transfer: Patient may need transfer to tertiary centre
• Refrigeration/storage: Facilities may have limited cold chain capability
• Group and screen: May not have been done previously
• Crossmatch: May require sending samples to distant laboratory
• Massive transfusion: May not be feasible in remote setting; early retrieval planning

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Follow-up 3: "The patient is now improving. What considerations for discharge and follow-up?"

Expected Answer:

• Transition planning: Early involvement of Aboriginal Health Workers
• Community support: Identify family/community supports
• Shared care: Coordinate with local health service, GP, community nurse
• Culturally appropriate follow-up: May prefer community clinic to hospital
• Reduce future transfusion need:
  • Investigate and treat iron deficiency
  • Manage underlying liver disease
  • Beta-blocker for variceal bleeding prophylaxis
  • Address modifiable risk factors
• Blood donor consideration: Encourage blood donation in Indigenous communities
• Documentation: Clear handover to community services

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Viva 6: Storage Lesion and Blood Product Quality

Stem: "A colleague suggests that we should only transfuse fresh blood (less than 7 days old) to critically ill patients because of the storage lesion. Discuss."

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Examiner Opening Question: "What is the storage lesion?"

Expected Answer:

• Progressive biochemical and structural changes during RBC storage at 2-6°C
• Changes include:
  • "2,3-DPG depletion: Left shift of oxygen-haemoglobin dissociation curve"
  • "ATP depletion: Impaired membrane integrity, reduced deformability"
  • "Potassium leak: May reach 50 mmol/L by Day 42"
  • "Microparticle release: Pro-inflammatory, pro-coagulant"
  • "Free haemoglobin release: NO scavenging, vasoconstriction"
  • "Lactate accumulation: Metabolic acidosis"
  • "Reduced deformability: Microcirculatory obstruction"
• These changes are demonstrable in vitro and early observational studies suggested harm

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Follow-up 1: "What is the clinical evidence regarding blood age?"

Expected Answer:

• ABLE Trial (Lacroix et al., NEJM 2015, PMID 26771531):
  • 2,430 critically ill patients
  • Fresh (less than 8 days) vs standard issue blood
  • 90-day mortality: 37.0% vs 35.3% (p=0.38)
  • No difference in any secondary outcomes
  • "Conclusion: Fresh blood not superior in ICU"
• RECESS Trial (Steiner et al., NEJM 2015, PMID 25901428):
  • 1,098 cardiac surgery patients
  • Fresh (less than 10 days) vs older (≥21 days)
  • No difference in MODS score or any secondary outcome
• INFORM Trial (Heddle et al., NEJM 2016, PMID 28319519):
  • 24,736 hospitalized patients
  • Fresh vs standard issue
  • No difference in in-hospital mortality
• Meta-analyses: No survival benefit with fresher blood

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Follow-up 2: "So should we never worry about blood age?"

Expected Answer:

• Generally, standard blood bank practices (first-in-first-out) are acceptable
• Potential exceptions (theoretical, not evidence-based):
  • "Neonates: Higher K+ sensitivity; may use fresher/washed blood"
  • "Massive transfusion: Theoretical concerns with very old blood"
  • "Exchange transfusion: May use fresher blood"
• 2,3-DPG recovery: Restores within 24-48 hours post-transfusion
• Potassium: Rapid redistribution; wash if concerned
• Pragmatic approach: Don't waste blood chasing "fresh" units
• Quality assured products: All blood within expiry is acceptable

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Follow-up 3: "What about whole blood vs component therapy?"

Expected Answer:

• Historical context: Whole blood was standard; component therapy developed to maximize donor utility
• Current resurgence: Whole blood for trauma resuscitation
• Advantages of whole blood:
  • "Balanced ratio (inherent 1:1:1)"
  • Lower total volume
  • Simpler logistics
  • Coagulation factors present
  • Reduced donor exposures
• Disadvantages:
  • Shorter shelf life (21 days)
  • ABO limitations
  • Cannot separate components
  • Limited availability
• Current use:
  • "Military: Warm fresh whole blood (WFWB) in combat"
  • "Civilian trauma: Some centres using LTOWB (low-titre O whole blood)"
  • Not routine in ICU

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References

Landmark Trials

1. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care (TRICC). N Engl J Med. 1999;340(6):409-417. PMID: 9971864

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

3. Mazer CD, Whitlock RP, Fergusson DA, et al. Restrictive or liberal red-cell transfusion for cardiac surgery (TRICS-III). N Engl J Med. 2017;377(22):2133-2144. PMID: 29116904

4. 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 (PROPPR). JAMA. 2015;313(5):471-482. PMID: 25647203

5. Curry N, Davenport R, Pavord S, et al. The use of viscoelastic haemostatic assays in the management of major bleeding: A British Society for Haematology Guideline. Br J Haematol. 2018;182(6):789-806. PMID: 30073664

6. Curry N, Rourke C, Davenport R, et al. Early cryoprecipitate for major haemorrhage in trauma (CRYOSTAT-2). Lancet. 2023;402(10399):410-420. PMID: 37587580

7. Lacroix J, Hebert PC, Fergusson DA, et al. Age of transfused blood in critically ill adults (ABLE). N Engl J Med. 2015;372(15):1410-1418. PMID: 26771531

8. Steiner ME, Ness PM, Assmann SF, et al. Effects of red-cell storage duration on patients undergoing cardiac surgery (RECESS). N Engl J Med. 2015;372(15):1419-1429. PMID: 25901428

9. Heddle NM, Cook RJ, Arnold DM, et al. Effect of short-term vs. long-term blood storage on mortality after transfusion (INFORM). N Engl J Med. 2016;375(20):1937-1945. PMID: 28319519

10. Carson JL, Stanworth SJ, Roubinian N, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:CD002042. PMID: 27731885

Guidelines and Consensus Statements

11. National Blood Authority (Australia). Patient Blood Management Guidelines. Canberra: NBA; 2022. https://www.blood.gov.au

12. ISBT Working Party on Haemovigilance. Proposed standard definitions for surveillance of non infectious adverse transfusion reactions. ISBT; 2019.

13. Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59(7):2465-2476. PMID: 30993742

14. Lieberman L, Maskens C, Goffa A, et al. Risk factors for transfusion-associated circulatory overload. Transfusion. 2019;59(3):893-901. PMID: 30681178

15. Roubinian NH, Hendrickson JE, Engel DJ, et al. Contemporary risk factors and outcomes of transfusion-associated circulatory overload. Crit Care Med. 2018;46(4):577-585. PMID: 29293150

Reviews and Meta-analyses

16. Carson JL, Triulzi DJ, Ness PM. Indications for and adverse effects of red-cell transfusion. N Engl J Med. 2017;377(13):1261-1272. PMID: 28953435

17. Slichter SJ. Platelet transfusion therapy. Hematol Oncol Clin North Am. 2007;21(4):697-729. PMID: 17666286

18. Murad MH, Stubbs JR, Gandhi MJ, et al. The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion. 2010;50(6):1370-1383. PMID: 20136719

19. Spinella PC, Cap AP. Whole blood: back to the future. Curr Opin Hematol. 2016;23(6):536-542. PMID: 27607603

20. Cap AP, Beckett A, Benov A, et al. Whole blood transfusion. Mil Med. 2018;183(suppl_2):44-51. PMID: 30189073

21. Napolitano LM, Kurek S, Luchette FA, et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37(12):3124-3157. PMID: 19773646

22. Bolliger D, Gorlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology. 2010;113(5):1205-1219. PMID: 20881594

Australian/Indigenous Health

23. Australian Indigenous HealthInfoNet. Overview of Aboriginal and Torres Strait Islander health status. Perth: Australian Indigenous HealthInfoNet; 2023.

24. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander Health Performance Framework 2020. Canberra: AIHW; 2020.

25. Cass A, Cunningham J, Snelling P, et al. End-stage renal disease in Indigenous Australians: a disease of disadvantage. Ethn Dis. 2002;12(3):373-378. PMID: 12148707

Additional Key References

26. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11-21. PMID: 23281973

27. Docherty AB, O'Donnell R, Brunskill S, et al. Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ. 2016;352:i1351. PMID: 27026510

28. Sarode R, Milling TJ, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding (INCH). Circulation. 2013;128(11):1234-1243. PMID: 23935011

29. Toy P, Popovsky MA, Abraham E, et al. Transfusion-related acute lung injury: definition and review. Crit Care Med. 2005;33(4):721-726. PMID: 15818095

30. Roback JD, Combs MR, Grossman BJ, et al. AABB Technical Manual. 18th ed. Bethesda: AABB; 2014.

31. British Committee for Standards in Haematology. Guidelines on the use of platelet transfusions. Br J Haematol. 2017;176(3):365-394. PMID: 28009056

32. Green L, Bolton-Maggs P, Beattie C, et al. British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products. Br J Haematol. 2018;181(1):54-75. PMID: 29527671

33. Stanworth SJ, Brunskill SJ, Hyde CJ, et al. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004;126(1):139-152. PMID: 15198745

34. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2015;162(3):205-213. PMID: 25383671

35. Wikkelsoe AJ, Johansen M, Langhoff-Roos J, et al. Fibrinogen concentrate for bleeding - a systematic review. Acta Anaesthesiol Scand. 2015;59(9):1081-1092. PMID: 26095023

36. Collins PW, Lilley G, Bruynseels D, et al. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood. 2014;124(11):1727-1736. PMID: 25024304

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

38. Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014;370(9):847-859. PMID: 24571757

39. Desborough MJ, Sandu R, Brunskill SJ, et al. Fresh frozen plasma for cardiovascular surgery. Cochrane Database Syst Rev. 2015;(7):CD007614. PMID: 26149468

40. Australian Red Cross Lifeblood. Blood Component Information Circular of Information. Melbourne: Australian Red Cross Lifeblood; 2023.

41. Isbister JP. The three-pillar matrix of patient blood management--an overview. Best Pract Res Clin Anaesthesiol. 2013;27(1):69-84. PMID: 23590917

42. 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

43. Tapia NM, Chang A, Norman M, et al. TEG-guided resuscitation is superior to standardized MTP resuscitation in massively transfused penetrating trauma patients. J Trauma Acute Care Surg. 2013;74(2):378-385. PMID: 23354228

44. Levy JH, Goodnough LT. How I use fibrinogen replacement therapy in acquired bleeding. Blood. 2015;125(9):1387-1393. PMID: 25519751

45. Leal-Noval SR, Munoz M, Asuero M, et al. Spanish Consensus Statement on alternatives to allogeneic blood transfusion. Blood Transfus. 2013;11(4):585-610. PMID: 24120598

46. Murphy WG. The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences. Blood Rev. 2014;28(2):41-47. PMID: 24491804

47. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT Study: Anemia and blood transfusion in the critically ill - current clinical practice in the United States. Crit Care Med. 2004;32(1):39-52. PMID: 14707558

48. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients (ABC). JAMA. 2002;288(12):1499-1507. PMID: 12243637

49. Rawn J. The silent risks of blood transfusion. Curr Opin Anaesthesiol. 2008;21(5):664-668. PMID: 18784493

50. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion. 2004;44(12):1774-1789. PMID: 15584994

51. Bennett-Guerrero E, Veldman TH, Doctor A, et al. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007;104(43):17063-17068. PMID: 17940021

52. Hess JR. Red cell changes during storage. Transfus Apher Sci. 2010;43(1):51-59. PMID: 20542731

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Related Topics

Prerequisites

• [[Coagulation Physiology]]
• [[Oxygen Delivery and Consumption]]
• [[Immunology Basics]]
• [[ABO Blood Group System]]

Related Conditions

• [[Massive Transfusion Protocol]]
• [[DIC]]
• [[HIT]]
• [[TTP-HUS]]

Complications

• [[TRALI and TACO]]
• [[Transfusion Reactions]]
• [[Hyperkalaemia]]

Procedures

• [[Blood Product Administration]]
• [[Viscoelastic Testing (TEG/ROTEM)]]

Pharmacology

• [[Tranexamic Acid]]
• [[Prothrombin Complex Concentrate]]
• [[Fibrinogen Concentrate]]