Massive Transfusion Protocol (Adult)

Overview

A massive transfusion protocol (MTP) is a standardized institutional approach to rapidly deliver large volumes of blood products to patients with life-threatening hemorrhage.[1] MTP activation streamlines blood bank processes, ensures balanced product ratios, and improves survival in hemorrhagic shock.

Clinical Pearl: Early MTP activation saves lives. Delays in blood product delivery increase mortality. When in doubt about hemorrhage severity, activate MTP early - it can always be deactivated.[2]

Definitions of massive transfusion:[3]

Exam Detail: FRCEM and MRCP commonly test MTP activation criteria (ABC score, Shock Index), blood product ratios (1:1:1), and management of transfusion complications (hypocalcemia, hypothermia, coagulopathy).

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Epidemiology

Incidence

Causes Requiring MTP

Trauma (50-60%):

• Penetrating torso trauma
• Blunt abdominal/pelvic trauma
• Major vascular injury
• Multiple long bone fractures

Obstetric (15-20%):

• Postpartum hemorrhage
• Placental abruption
• Uterine rupture
• Placenta accreta spectrum

Gastrointestinal (10-15%):

• Variceal hemorrhage
• Peptic ulcer bleeding
• Aortoenteric fistula

Surgical/Other (10-15%):

• Ruptured AAA
• Cardiac surgery
• Liver transplantation
• Coagulopathy with bleeding

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Aetiology and Pathophysiology

Coagulopathy of Massive Hemorrhage

Multiple factors contribute to coagulopathy during massive hemorrhage:[4]

1. Dilutional coagulopathy:

• Crystalloid resuscitation dilutes clotting factors
• Each liter crystalloid reduces factor levels by ~10%
• Fibrinogen particularly affected (falls early)

2. Consumptive coagulopathy:

• Ongoing hemorrhage consumes clotting factors and platelets
• DIC-like picture may develop
• Fibrinolysis activation

3. Acute traumatic coagulopathy (ATC):

• Present in 25-35% on arrival (before resuscitation)
• Hypoperfusion-induced protein C activation
• Systemic anticoagulation and hyperfibrinolysis
• Independent predictor of mortality

4. Hypothermia:

• Impairs enzymatic function of coagulation cascade
• Reduces platelet function
• Not corrected by standard laboratory tests (run at 37°C)

5. Acidosis:

• pH > 7.2 significantly impairs factor activity
• Reduces thrombin generation
• Worsens with ongoing hypoperfusion

6. Hypocalcemia:

• Citrate in blood products chelates ionized calcium
• Calcium essential for coagulation cascade
• Often overlooked cause of ongoing coagulopathy

Clinical Pearl: The "bloody vicious cycle": Hypothermia, acidosis, and coagulopathy each worsen the others. Breaking this cycle requires aggressive warming, hemorrhage control, and balanced resuscitation - not more crystalloid.[4]

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Clinical Presentation

Recognition of Need for MTP

Clinical indicators:

• Obvious major external hemorrhage
• Hemodynamic instability despite initial resuscitation
• Rapidly expanding hematoma
• Penetrating injury to torso/proximal extremity
• Unstable pelvic fracture
• Ongoing need for blood products

Physiological signs:

• SBP > 90 mmHg
• Heart rate greater than 120 bpm
• Shock Index (HR/SBP) greater than 1.0
• Altered mental status
• Cold, mottled extremities
• Weak, thready pulse

Prediction Scores

ABC Score (Assessment of Blood Consumption):[5]

Score ≥2: Activate MTP

• Sensitivity: 75-85%
• Specificity: 75-88%
• PPV: 40-50%, NPV: 95%

Shock Index:

• SI = Heart Rate / Systolic BP
• SI greater than 1.0: High risk for massive transfusion
• SI greater than 1.4: Very high risk

Other scores:

• TASH score (Trauma-Associated Severe Hemorrhage)
• McLaughlin score
• Revised MTS criteria

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Investigations

Immediate Investigations

Point-of-Care Testing

Viscoelastic testing (TEG/ROTEM):[6]

• Provides real-time assessment of clot formation and lysis
• Guides targeted blood product therapy
• Faster results than conventional tests (15-30 min vs 45-60 min)
• Reduces blood product usage by 20-30%

TEG parameters and treatment:

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Management

MTP Activation

Who can activate:

• Emergency physician
• Trauma surgeon
• Anesthesiologist
• Critical care physician
• Obstetric consultant (for obstetric hemorrhage)

How to activate:

• Single phone call to blood bank
• Provide patient identifiers
• State "Activate Massive Transfusion Protocol"
• Blood bank prepares pre-packaged products

Blood Product Delivery

Standard MTP cooler contents (institutional variation):[7]

Ratio strategy (1:1:1):[8]

• Based on PROPPR trial evidence
• 1 unit pRBC : 1 unit FFP : 1 unit platelets
• Mimics whole blood composition
• Reduces mortality and achieves hemostasis faster

Whole blood (if available):

• Increasingly used in trauma centers
• Low-titer group O whole blood for initial resuscitation
• Reduces product complexity and improves logistics

Initial Resuscitation

Before MTP products arrive:

• O-negative (or O-positive for males) pRBCs immediately
• Minimize crystalloid (maximum 1-2 L total)
• Activate hemorrhage control measures
• Tranexamic acid 1g IV if within 3 hours of injury

Transfusion sequence:

1. Start with pRBCs and FFP simultaneously
2. Add platelets with second cooler
3. Continue until hemorrhage controlled
4. De-escalate once stable

Adjunctive Therapies

Tranexamic acid (TXA):[9]

• Dose: 1g IV over 10 minutes, then 1g over 8 hours
• Give within 3 hours of injury (harm if greater than 3 hours in trauma)
• Reduces mortality by 10-15% in bleeding trauma
• Also effective in PPH, surgical bleeding

Calcium replacement:[10]

• Citrate in blood products chelates calcium
• Monitor ionized calcium with each cooler
• Treat if iCa > 1.1 mmol/L
• Calcium chloride 1g IV (10 mL of 10%) - preferred (3× more elemental calcium)
• Calcium gluconate 1g IV if peripheral access only

Fibrinogen replacement:[11]

• Target fibrinogen greater than 1.5-2 g/L
• Cryoprecipitate: 10 units = ~2.5g fibrinogen
• Fibrinogen concentrate: 2-4g IV (faster, no thaw time)
• Give early if fibrinogen > 1.5 g/L on arrival

Factor concentrates:

• Prothrombin complex concentrate (PCC): For warfarin reversal or factor deficiency
• Factor VIIa: Last resort for refractory coagulopathy (off-label, thrombosis risk)

Temperature Management

Prevention of hypothermia:

• Blood warmers for all products (mandatory)
• Forced air warming blankets
• Warm IV fluids
• Increase ambient temperature
• Remove wet clothing
• Target temperature greater than 36°C

Monitoring During MTP

Continuous monitoring:

• Heart rate, blood pressure, SpO₂
• Urine output (target greater than 0.5 mL/kg/hr)
• Temperature
• Mental status

Serial laboratory monitoring (every 30-60 min):

• ABG with lactate and ionized calcium
• Hemoglobin
• Coagulation panel (PT, APTT, fibrinogen)
• Platelet count
• Viscoelastic testing if available

Endpoints of resuscitation:

• Hemorrhage controlled
• Hemodynamically stable (MAP ≥65 mmHg off vasopressors)
• Lactate normalizing (> 2 mmol/L)
• Base deficit improving
• Coagulopathy correcting
• Temperature greater than 36°C

MTP Deactivation

When to deactivate:

• Hemorrhage definitively controlled
• Patient hemodynamically stable
• No longer requiring rapid transfusion
• Transitioning to maintenance transfusion

Process:

• Notify blood bank
• Return unused products promptly
• Document products used
• Complete MTP audit form

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Complications

Transfusion-Related Complications

Hypocalcemia Management

Symptoms of hypocalcemia:

• Perioral tingling
• Muscle cramps, tetany
• QT prolongation, arrhythmias
• Hypotension (calcium needed for cardiac contractility)
• Worsening coagulopathy

Treatment:

• Calcium chloride 10 mL (1g) IV via central line
• Calcium gluconate 10-30 mL (1-3g) IV if peripheral
• Repeat every 4-6 units of blood products
• Target iCa greater than 1.1 mmol/L

Clinical Pearl: Hypocalcemia is the most common preventable complication of massive transfusion. Proactive calcium replacement (1g CaCl₂ per cooler) reduces hemodynamic instability and improves coagulation.[10]

Hyperkalemia in MTP

Causes:

• Potassium leakage from stored RBCs (older units higher K⁺)
• Cellular lysis from rapid transfusion
• Acidosis driving K⁺ out of cells
• Renal dysfunction from shock

Management:

• Calcium chloride (cardioprotection)
• Insulin 10 units + 50 mL 50% dextrose (shift K⁺ intracellularly)
• Use fresher blood products when possible (> 14 days)
• Dialysis if refractory

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Prognosis

Outcomes

Survival by Etiology

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Key Guidelines

1. TQIP Massive Transfusion in Trauma Guidelines (2020)[1]
2. European Trauma Guidelines (2023): Management of Bleeding and Coagulopathy[12]
3. AABB Guidelines: Red Blood Cell Transfusion[13]
4. NICE 2015: Blood Transfusion[14]

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Exam Scenarios

SBA Question 1

Scenario: A 32-year-old man is brought to the ED after a stab wound to the abdomen. His BP is 75/50 mmHg, HR 135 bpm, and FAST is positive. Using the ABC score, what is his score and should MTP be activated?

A) Score 2, do not activate MTP
B) Score 3, activate MTP
C) Score 4, activate MTP
D) Score 1, do not activate MTP
E) Score 2, consider activation based on clinical judgment

Answer

Answer: C) Score 4, activate MTP

ABC Score calculation:

• Penetrating mechanism: +1
• SBP ≤90 mmHg: +1
• HR ≥120: +1
• Positive FAST: +1
• Total: 4 points

Score ≥2 indicates MTP activation. This patient meets all four criteria and requires immediate MTP activation.[5]

SBA Question 2

Scenario: During massive transfusion, the patient's ionized calcium is 0.85 mmol/L. What is the most appropriate treatment?

A) Calcium gluconate 1g IV via peripheral line
B) Calcium chloride 1g IV via central line
C) Oral calcium carbonate 1g
D) No treatment needed, monitor only
E) Magnesium sulfate 2g IV

Answer

Answer: B) Calcium chloride 1g IV via central line

Ionized calcium > 1.1 mmol/L during MTP requires treatment. Calcium chloride is preferred because it provides 3× more elemental calcium than calcium gluconate and doesn't require hepatic metabolism.[10]

If only peripheral access is available, calcium gluconate is acceptable to avoid risk of tissue necrosis from extravasation.

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Viva Scenario

Examiner: "You activate MTP for a trauma patient. The first cooler arrives with 6 units pRBCs and 6 units FFP. Talk me through your transfusion strategy."

Candidate: "I would transfuse in a 1:1:1 ratio, starting pRBCs and FFP simultaneously through blood warmers. I would request platelets with the second cooler.

Immediate actions:

• Both products through blood warmers via large-bore IV
• Send baseline bloods: Hb, coag, fibrinogen, iCa, ABG
• Give TXA 1g IV if within 3 hours of injury
• Active warming with forced air blanket

Monitoring every 30 minutes:

• Repeat Hb, coagulation, fibrinogen, ionized calcium
• ABG for pH, lactate, base deficit
• Temperature

Adjuncts:

• Calcium chloride 1g after each cooler (or if iCa > 1.1)
• Fibrinogen replacement if > 1.5 g/L (cryoprecipitate 10 units or fibrinogen concentrate 4g)
• Continue until hemorrhage controlled

Endpoints:

• Hemorrhage controlled
• MAP ≥65 mmHg
• Lactate normalizing
• Coagulopathy correcting
• Temperature greater than 36°C"

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References

1. American College of Surgeons Trauma Quality Programs. Massive Transfusion in Trauma Guidelines. Chicago, IL: ACS; 2020.

2. Holcomb JB, del Junco DJ, Fox EE, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study. JAMA Surg. 2013;148(2):127-136. doi:10.1001/2013.jamasurg.387

3. Savage SA, Zarzaur BL, Croce MA, Fabian TC. Redefining massive transfusion when every second counts. J Trauma Acute Care Surg. 2013;74(2):396-400. doi:10.1097/TA.0b013e31827a3639

4. Brohi K, Cohen MJ, Ganter MT, et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008;64(5):1211-1217. doi:10.1097/TA.0b013e318169cd3c

5. Nunez TC, Voskresensky IV, Dossett LA, et al. Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)? J Trauma. 2009;66(2):346-352. doi:10.1097/TA.0b013e3181961c35

6. 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. doi:10.1097/SLA.0000000000001608

7. Cotton BA, Dossett LA, Au BK, et al. Room for (performance) improvement: provider-related factors associated with poor outcomes in massive transfusion. J Trauma. 2009;67(5):1004-1012. doi:10.1097/TA.0b013e3181bcb2a8

8. 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. doi:10.1001/jama.2015.12

9. 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. doi:10.1016/S0140-6736(10)60835-5

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. doi:10.1177/0310057X1103900107

11. Rourke C, Curry N, Khan S, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10(7):1342-1351. doi:10.1111/j.1538-7836.2012.04752.x

12. Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80. doi:10.1186/s13054-023-04327-7

13. Carson JL, Guyatt G, Heddle NM, et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316(19):2025-2035. doi:10.1001/jama.2016.9185

14. National Institute for Health and Care Excellence. Blood transfusion. NICE guideline [NG24]. 2015.

15. Spinella PC, Perkins JG, Grathwohl KW, et al. Warm fresh whole blood is independently associated with improved survival for patients with combat-related traumatic injuries. J Trauma. 2009;66(4 Suppl):S69-S76. doi:10.1097/TA.0b013e31819d85fb

16. Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007;63(4):805-813. doi:10.1097/TA.0b013e3181271ba3

17. Duchesne JC, Kimonis K, Marr AB, et al. Damage control resuscitation in combination with damage control laparotomy: a survival advantage. J Trauma. 2010;69(1):46-52. doi:10.1097/TA.0b013e3181df91fa

18. Shaz BH, Dente CJ, Nicholas J, et al. Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients. Transfusion. 2010;50(2):493-500. doi:10.1111/j.1537-2995.2009.02414.x

19. Johansson PI, Stensballe J. Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets--a review of the current literature. Transfusion. 2010;50(3):701-710. doi:10.1111/j.1537-2995.2009.02458.x

20. Nascimento B, Callum J, Tien H, et al. Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results-guided transfusion in patients with severe trauma: a randomized feasibility trial. CMAJ. 2013;185(12):E583-E589. doi:10.1503/cmaj.121986

21. Stanworth SJ, Davenport R, Curry N, et al. Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice. Br J Surg. 2016;103(4):357-365. doi:10.1002/bjs.10052

22. Callcut RA, Cotton BA, Muskat P, et al. Defining when to initiate massive transfusion: a validation study of individual massive transfusion triggers in PROMMTT patients. J Trauma Acute Care Surg. 2013;74(1):59-65. doi:10.1097/TA.0b013e3182788b34