Transfusion in Critical Care — Part 3: Massive Transfusion & Hemorrhage Management

Massive transfusion protocol activation, fixed-ratio transfusion (1:1:1 per PROPPR), TEG/ROTEM viscoelastic testing and interpretation, damage control resuscitation, TXA (CRASH-2), calcium replacement, permissive hypotension, and hemorrhage management in trauma, obstetric, and GI bleeding.

guidelinesMar 2026guidelines

1. Definition and Scope

1.1 Definitions of Massive Transfusion

DefinitionCriteriaNotes
Classic definition≥ 10 units pRBC in 24 hoursMost commonly cited; identifies patients retrospectively
Alternative (time-sensitive)≥ 4 units pRBC in 1 hour with ongoing bleeding anticipatedMore clinically useful for prospective MTP activation
Critical administration threshold (CAT)≥ 3 units pRBC in 1 hourUsed in some trauma systems as an early activation trigger
Replacement of entire blood volumeReplacement of ≥ 1 blood volume (approximately 70 mL/kg) in 24 hoursPhysiologic definition
Pediatric definition≥ 40 mL/kg of all blood products in 24 hours, or replacement of > 50% blood volume in 3 hoursWeight-based for children

1.2 Epidemiology

  • Massive transfusion is required in approximately 3–5% of civilian trauma admissions and 8–10% of military trauma casualties
  • Uncontrolled hemorrhage accounts for 30–40% of trauma deaths and is the leading preventable cause of death after injury
  • Non-trauma causes of massive hemorrhage include obstetric hemorrhage, gastrointestinal bleeding, ruptured aortic aneurysm, and intraoperative/postoperative surgical bleeding

2. Massive Transfusion Protocol (MTP) Activation

2.1 Activation Criteria

The MTP should be activated based on clinical assessment of hemorrhage severity, not laboratory values (which lag behind the clinical picture in acute hemorrhage). Validated scoring systems can assist with the decision to activate.1

Assessment of Blood Consumption (ABC) Score

ComponentCriteriaPoints
Penetrating mechanismYes1
Systolic BP in ED≤ 90 mmHg1
Heart rate in ED≥ 120 bpm1
Positive FAST examFree fluid on bedside ultrasound1

Interpretation: ABC Score ≥ 2 predicts need for massive transfusion with sensitivity ~75% and specificity ~85%.1

Shock Index

ParameterDefinitionInterpretation
Shock Index (SI)Heart Rate ÷ Systolic Blood PressureNormal: 0.5–0.7
SI > 0.9: Suggests significant hemorrhage
SI > 1.0: Strongly associated with need for massive transfusion
SI > 1.4: Predictive of massive transfusion and high mortality

Additional Clinical Triggers for MTP Activation

  • Hemodynamic instability (SBP < 90 mmHg) with suspected hemorrhagic etiology that is refractory to initial crystalloid bolus
  • Estimated blood loss > 1,500 mL (Class III hemorrhage)
  • Clinical gestalt of the trauma team leader or attending physician
  • Ongoing hemorrhage requiring surgical or interventional radiology control

2.2 MTP Component Delivery — Fixed-Ratio Strategy

The landmark Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial established the evidence base for balanced-ratio massive transfusion.2

PROPPR Trial Summary

Parameter1:1:1 Group1:1:2 Group
Ratio (Plasma : Platelets : RBC)1 unit plasma : 1 dose platelets : 1 unit RBC1 unit plasma : 1 dose platelets : 2 units RBC
24-hour mortality12.7%17.0% (p = 0.12)
30-day mortality22.4%26.1% (p = 0.26)
Hemostasis achieved at 24 hours86%78% (p = 0.006)
Exsanguination within 24 hours9.2%14.6% (p = 0.03)

Key findings: The 1:1:1 ratio resulted in significantly more patients achieving hemostasis and fewer deaths due to exsanguination at 24 hours. While 24-hour and 30-day all-cause mortality differences did not reach statistical significance, the trend favored 1:1:1. There was no increase in complications (ARDS, VTE, sepsis) with higher plasma and platelet ratios.2

Standard MTP Pack Contents

Most institutions deliver blood products in standardized MTP packs (“coolers”) at predefined intervals. The following represents a common MTP delivery structure:

MTP PackContentsNotes
Pack 1 (Immediate)6 units pRBC (uncrossmatched O-neg or O-pos) + 4 units thawed plasma (AB or type-specific if available)Issued immediately upon MTP activation; some centers include TXA with first pack
Pack 2 (15–30 min)6 units pRBC + 4 units plasma + 1 dose apheresis plateletsType-specific blood once available
Pack 3 and subsequent6 units pRBC + 4 units plasma + 1 dose platelets + 10 units cryoprecipitateContinue until MTP deactivated; adjust based on labs and POC testing

Approximate ratio: This delivers components in approximately a 1:1:1 ratio by therapeutic dose (not by volume):

  • 6 units RBC ≈ 1,800 mL
  • 4 units plasma ≈ 800–1,000 mL
  • 1 dose platelets ≈ 250–300 mL
  • 10 units cryoprecipitate ≈ 100–150 mL

2.3 MTP Laboratory Monitoring

During active massive transfusion, laboratory values should be obtained at defined intervals to guide ongoing component therapy:

TestFrequency During MTPTarget
CBC (hemoglobin, platelets)Every 30–60 minutes (or after every MTP pack)Hb > 7 g/dL; Platelets > 50,000/μL (> 100,000/μL in TBI)
PT/INREvery 30–60 minutesINR < 1.5
FibrinogenEvery 30–60 minutes> 150–200 mg/dL
Ionized calciumEvery 30–60 minutes≥ 1.1 mmol/L (4.4 mg/dL)
Arterial blood gas (pH, base deficit, lactate)Every 30–60 minutespH > 7.2; Base deficit < −6; Lactate trending down
TEG/ROTEM (if available)At MTP activation and every 30–60 minutesSee Section 3 for interpretation

3. Point-of-Care Viscoelastic Testing — TEG and ROTEM

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care (POC) viscoelastic hemostatic assays that provide a real-time, comprehensive assessment of the entire coagulation cascade — from initial clot formation through fibrinolysis — in whole blood. These tests enable goal-directed transfusion therapy, reducing empiric blood product administration and improving patient outcomes in hemorrhage management.3 4

3.1 TEG and ROTEM — Parameter Comparison

Property MeasuredTEG ParameterROTEM ParameterNormal Range (TEG)Normal Range (ROTEM)Clinical Interpretation
Time to initial clot formation (coagulation factor activity)R (Reaction time)CT (Clotting time)5–10 minEXTEM CT: 38–79 s; INTEM CT: 100–240 sProlonged → Factor deficiency or anticoagulant effect → Give FFP/plasma or PCC
Clot kinetics (fibrinogen and platelet interaction, initial clot strengthening)K (Kinetics time)CFT (Clot formation time)1–3 minEXTEM CFT: 34–159 sProlonged → Low fibrinogen or platelet dysfunction → Give cryoprecipitate or platelets
Rate of clot strengtheningα-angle (Alpha angle)α-angle53–72°EXTEM α: 63–83°Decreased → Low fibrinogen or platelet dysfunction → Give cryoprecipitate or platelets
Maximum clot strength (platelet function and fibrinogen)MA (Maximum amplitude)MCF (Maximum clot firmness)50–70 mmEXTEM MCF: 50–72 mmDecreased → Platelet dysfunction or low fibrinogen → Give platelets (if FIBTEM MCF normal, platelet dysfunction is cause)
Fibrinogen contribution to clot strengthFunctional Fibrinogen (FF) – TEG-FF MAFIBTEM MCF (A5 or A10 for rapid assessment)FF MA: 15–32 mmFIBTEM MCF: 9–25 mm; FIBTEM A5: 6–21 mmDecreased → Fibrinogen deficiency → Give cryoprecipitate or fibrinogen concentrate
Clot stability / FibrinolysisLY30 (Lysis at 30 min)ML (Maximum lysis); LI30 (Lysis index at 30 min)LY30: 0–7.5%EXTEM ML < 15%; EXTEM LI30 > 94%Increased lysis → Hyperfibrinolysis → Give TXA

3.2 ROTEM-Specific Assays

ROTEM AssayActivatorWhat It MeasuresClinical Use
EXTEMTissue factor (extrinsic pathway)Overall extrinsic coagulation pathway; clot formation and firmnessScreening test; prolonged CT → factor deficiency; low MCF → platelet or fibrinogen problem
INTEMEllagic acid (intrinsic pathway)Intrinsic pathway activationEvaluates heparin effect (compare with HEPTEM)
FIBTEMTissue factor + cytochalasin D (platelet inhibitor)Fibrinogen contribution to clot strength (isolates fibrinogen by inhibiting platelets)Low FIBTEM MCF/A5 → fibrinogen deficiency → give cryoprecipitate/fibrinogen concentrate
HEPTEMEllagic acid + heparinaseIntrinsic pathway with heparin neutralizationCompare with INTEM: if INTEM CT prolonged but HEPTEM CT normal → heparin effect confirmed; give protamine
APTEMTissue factor + aprotinin (antifibrinolytic)Extrinsic pathway with fibrinolysis inhibitionCompare with EXTEM: if EXTEM shows lysis but APTEM does not → hyperfibrinolysis confirmed; give TXA

3.3 TEG/ROTEM-Guided Transfusion Algorithm

The following algorithm provides a systematic approach to goal-directed transfusion based on viscoelastic testing results:3 4

Step 1 — Is there hyperfibrinolysis?

  • TEG: LY30 > 7.5% → Give TXA (1 g IV bolus)
  • ROTEM: EXTEM ML > 15% or EXTEM LI30 < 94% → Give TXA (1 g IV bolus)
  • Confirm with APTEM (ROTEM): if APTEM normalizes compared to EXTEM → fibrinolysis confirmed

Step 2 — Is clot initiation adequate? (Coagulation factor assessment)

  • TEG: R > 10 min → Give FFP 10–15 mL/kg (or PCC if warfarin-related)
  • ROTEM: EXTEM CT > 79 s → Give FFP 10–15 mL/kg
  • ROTEM: INTEM CT prolonged but HEPTEM CT normal → Give protamine (heparin effect)

Step 3 — Is fibrinogen adequate?

  • TEG: FF MA < 15 mm → Give cryoprecipitate 10 units or fibrinogen concentrate 2–4 g
  • ROTEM: FIBTEM A5 < 6 mm or FIBTEM MCF < 9 mm → Give cryoprecipitate 10 units or fibrinogen concentrate 2–4 g
  • Target: FIBTEM A5 ≥ 8–12 mm (some cardiac surgery protocols use higher targets)

Step 4 — Is platelet function/contribution adequate?

  • TEG: MA < 50 mm (with adequate FF) → Give platelets 1 apheresis dose
  • ROTEM: EXTEM MCF < 50 mm (with FIBTEM MCF ≥ 9 mm) → Give platelets 1 apheresis dose
  • The difference between EXTEM MCF and FIBTEM MCF reflects the platelet contribution to clot strength

Step 5 — Reassess

  • Repeat TEG/ROTEM after intervention (typically 15–30 minutes)
  • Continue algorithm until hemostasis achieved or MTP deactivated

3.4 Advantages of POC Viscoelastic Testing Over Conventional Labs

FeatureTEG/ROTEMConventional Labs (PT/INR, aPTT, Fibrinogen, Platelet Count)
Turnaround time10–20 minutes (some parameters available at 5 min)30–60 minutes
Whole blood testingYes — reflects in vivo hemostasis more accuratelyNo — performed on plasma (PT, aPTT) or whole blood (platelet count)
Detects fibrinolysisYes — LY30 (TEG), ML/LI30 (ROTEM)No — standard labs do not detect fibrinolysis
Identifies platelet dysfunctionYes — MA/MCF reflects functional platelet contributionNo — platelet count does not assess function
Identifies fibrinogen deficiency specificallyYes — FF (TEG), FIBTEM (ROTEM) isolate fibrinogen contributionPartially — Clauss fibrinogen assay provides a quantitative level but not functional contribution
Identifies heparin effectYes — HEPTEM vs INTEM comparison (ROTEM)Partially — aPTT prolongation suggests heparin but not specific
Goal-directed transfusionEnables algorithm-driven component therapyEmpiric transfusion based on lab values

4. Damage Control Resuscitation (DCR)

Damage control resuscitation is an integrated approach to the management of hemorrhagic shock that combines hemostatic resuscitation, permissive hypotension, avoidance of crystalloid-mediated hemodilution, and early definitive hemorrhage control. DCR addresses the “lethal triad” of trauma — hypothermia, acidosis, and coagulopathy — which together create a self-reinforcing cycle of worsening hemorrhage.5

4.1 Principles of Damage Control Resuscitation

PrincipleImplementationRationale
Permissive hypotensionTarget SBP 80–90 mmHg (MAP 50–60 mmHg) until surgical hemorrhage control achievedAvoids disruption of nascent clot formation by excessive blood pressure; reduces ongoing hemorrhage; demonstrated mortality benefit in penetrating trauma
Limit crystalloidMinimize crystalloid infusion (avoid > 1–1.5 L in the first hour); use blood products for volume resuscitationCrystalloid causes dilutional coagulopathy, hypothermia, and acidosis; contributes to “resuscitation injury”
Balanced-ratio transfusion1:1:1 ratio (RBC : Plasma : Platelets) per PROPPR trialPrevents dilutional coagulopathy; replaces consumed factors and platelets in proportion to blood loss
Early TXATranexamic acid 1 g IV bolus + 1 g IV over 8 hours; administer within 3 hours of injuryReduces mortality from hemorrhage by 15–20% (CRASH-2); most effective when given early; DO NOT give > 3 hours post-injury
Calcium replacementMonitor ionized calcium every 30–60 minutes; replace to maintain iCa ≥ 1.1 mmol/LCitrate in blood products chelates calcium; hypocalcemia impairs coagulation cascade and cardiac contractility
Temperature managementActive warming: forced-air warming blankets, fluid warmers, increase ambient temperatureHypothermia impairs coagulation enzyme function and platelet aggregation; coagulation is essentially non-functional below 34°C
Damage control surgeryAbbreviated initial surgery focused on hemorrhage control and contamination containment → ICU resuscitation → planned return to ORAvoids prolonged initial surgery in physiologically depleted patients

4.2 Permissive Hypotension — Detailed Guidance

PopulationTarget SBPNotes
Penetrating trauma60–70 mmHg (or palpable radial pulse)Strongest evidence for permissive hypotension; Bickell et al. demonstrated mortality benefit6
Blunt trauma (without TBI)80–90 mmHgLess robust evidence than penetrating trauma; some guidelines recommend conventional targets
Traumatic brain injurySBP ≥ 100–110 mmHg (avoid hypotension)Permissive hypotension is contraindicated in TBI — even a single episode of SBP < 90 mmHg doubles mortality in TBI; maintain cerebral perfusion pressure (CPP) ≥ 60 mmHg
Spinal cord injuryMAP ≥ 85 mmHgMaintain spinal cord perfusion pressure
Elderly (age > 65)Consider higher targets (SBP ≥ 100 mmHg)Reduced physiologic reserve; chronic hypertension shifts autoregulation curve

4.3 Tranexamic Acid (TXA) — CRASH-2 Trial and Clinical Application

CRASH-2 Trial Summary7

ParameterValue
DesignMulticenter (274 hospitals, 40 countries), randomized, double-blind, placebo-controlled
Population20,211 adult trauma patients with significant hemorrhage or at risk of significant hemorrhage, within 8 hours of injury
InterventionTXA 1 g IV bolus over 10 min + 1 g IV infusion over 8 hours vs placebo
Primary outcomeAll-cause 28-day mortality
Results — All-cause mortality14.5% (TXA) vs 16.0% (placebo); RR 0.91 (95% CI, 0.85–0.97; p = 0.0035)
Results — Death due to bleeding4.9% (TXA) vs 5.7% (placebo); RR 0.85 (95% CI, 0.76–0.96; p = 0.0077)
Time-dependent effectTreatment within 1 hour: RR 0.68; within 1–3 hours: RR 0.79; after 3 hours: RR 1.44 (increased mortality — harm)
Thrombotic eventsNo increase in VTE, PE, MI, or stroke with TXA
SeizuresNot significantly increased in CRASH-2 (but high-dose TXA in cardiac surgery has been associated with seizures)

TXA Dosing Protocol

IndicationDoseTimingNotes
Trauma with significant hemorrhage1 g IV bolus over 10 min + 1 g IV infusion over 8 hoursWithin 3 hours of injury; ideally within 1 hourDo NOT administer > 3 hours post-injury (associated with increased mortality)
Massive transfusion (non-trauma)1 g IV bolus + 1 g over 8 hoursAs early as possibleExtrapolated from CRASH-2; less robust evidence in non-trauma massive hemorrhage
Postpartum hemorrhage1 g IV bolus over 10 min; second dose of 1 g if bleeding continues after 30 min or recurs within 24 hoursWithin 3 hours of deliveryWOMAN trial: reduced death due to bleeding (1.5% vs 1.9%; p = 0.045)8
Cardiac surgery (prophylactic)Loading dose: 10–30 mg/kg IV before incision; Maintenance: 1–16 mg/kg/h intraoperatively; Additional dose into CPB circuitBefore incisionReduces bleeding and transfusion requirements by 30–40%; seizure risk increases at higher doses (> 100 mg/kg cumulative)
Orthopedic surgery1 g IV before incision; optional second 1 g dose 3–6 hours laterBefore tourniquet release or incisionWell-established benefit in hip and knee arthroplasty

4.4 Calcium Replacement During Massive Transfusion

Citrate anticoagulant in stored blood products binds ionized calcium. During massive transfusion, the citrate load overwhelms hepatic metabolism, causing progressive hypocalcemia. Ionized calcium is essential for coagulation factor enzymatic activity and cardiac contractility.9

ParameterGuideline
Monitoring frequencyEvery 30–60 minutes during MTP (or with each ABG)
Target ionized calcium≥ 1.1 mmol/L (4.4 mg/dL)
Critical threshold< 0.9 mmol/L — associated with cardiovascular collapse and coagulopathy
Replacement — Calcium chloride (CaCl₂ 10%)1 g (10 mL of 10% solution) IV over 10 min via central line; may repeat every 15–30 min as needed
Replacement — Calcium gluconate (10%)3 g (30 mL of 10% solution) IV over 10–20 min; may give peripherally (less caustic)
Calcium chloride vs gluconateCaCl₂ provides 3× the elemental calcium per gram (272 mg vs 93 mg); CaCl₂ preferred in emergencies but requires central line (vesicant); calcium gluconate is safer peripherally
Rate of citrate metabolismHealthy liver metabolizes ~3 g citrate per 5 minutes; impaired in liver disease, hypothermia, and shock

Clinical pearl: A practical approach is to administer 1 g calcium chloride IV for every 4 units of blood products transfused, with adjustments based on ionized calcium levels.

4.5 Temperature Management — Prevention of Hypothermia

InterventionDetails
Fluid warmersAll IV fluids and blood products should be administered through inline fluid warmers set to 37–42°C during MTP
Forced-air warmingApply forced-air warming blankets (e.g., Bair Hugger) to all exposed body surfaces
Increase ambient temperatureIncrease OR/trauma bay/ICU room temperature to ≥ 24°C (ideally 28°C)
Remove wet drapes/clothingWet surfaces promote evaporative heat loss
Warm body cavity lavageWarmed saline (38–40°C) for thoracic or peritoneal lavage during damage control surgery
Target temperatureMaintain core temperature ≥ 36°C; temperatures < 34°C are associated with clinically significant coagulopathy

5. Hemorrhage Management by Clinical Context

5.1 Trauma Hemorrhage

PhaseActions
PrehospitalApply direct pressure and tourniquets; minimize crystalloid (may give 250 mL boluses to maintain radial pulse); administer TXA if available (1 g IV bolus); keep patient warm
Emergency departmentActivate MTP if ABC score ≥ 2 or clinical judgment; type and crossmatch; TXA 1 g IV bolus (+ 1 g over 8h); initiate massive transfusion per protocol; permissive hypotension (SBP 80–90 unless TBI); FAST ultrasound; send labs including TEG/ROTEM
Hemorrhage controlDamage control surgery (abbreviated laparotomy/thoracotomy for hemorrhage and contamination control); interventional radiology for pelvic hemorrhage, solid organ injury, vascular injury; pelvic binder for unstable pelvic fracture
ICU phaseContinue resuscitation to physiologic endpoints (lactate clearance, base deficit normalization, pH > 7.35); transition from empiric to goal-directed transfusion (lab/TEG/ROTEM-guided); rewarm to normothermia; correct coagulopathy; plan definitive repair at 24–48 hours

5.2 Obstetric Hemorrhage

Postpartum hemorrhage (PPH) is defined as blood loss ≥ 1,000 mL or blood loss accompanied by signs of hypovolemia within 24 hours of delivery.8

StepActions
1. Recognize and quantifyQuantitative blood loss measurement (QBL) — weigh blood-soaked materials; cumulative QBL > 500 mL (vaginal) or > 1,000 mL (cesarean) → initiate PPH protocol
2. Uterotonic agentsOxytocin 40 units in 1 L NS IV; methylergonovine 0.2 mg IM (avoid in hypertension); carboprost (15-methyl PGF₂α) 250 μg IM q15–90 min (avoid in asthma); misoprostol 600–1,000 μg sublingual/rectal
3. TXA1 g IV over 10 min; second 1 g dose if bleeding continues after 30 min (WOMAN trial evidence)8
4. TransfusionActivate MTP for ongoing hemorrhage with instability; fixed-ratio transfusion (1:1:1); monitor fibrinogen closely — fibrinogen < 200 mg/dL is a strong predictor of severe PPH; replace aggressively with cryoprecipitate or fibrinogen concentrate
5. ProceduresIntrauterine balloon tamponade (Bakri balloon); uterine compression sutures (B-Lynch); uterine artery embolization (IR); hysterectomy as last resort
6. MonitorSerial CBC, coagulation studies, fibrinogen q30–60 min; ionized calcium; TEG/ROTEM if available

5.3 Gastrointestinal Hemorrhage

PrincipleRecommendation
Transfusion thresholdHb ≤ 7 g/dL for hemodynamically stable patients (Villanueva et al.)10
Active hemorrhagic shockDo not wait for Hb threshold; resuscitate with MTP and pursue emergent endoscopy or surgery
Restrictive vs liberal evidenceThe Villanueva trial demonstrated that a restrictive threshold (Hb < 7 g/dL) resulted in significantly lower 45-day mortality (5% vs 9%) and lower rebleeding rates compared to a liberal threshold (Hb < 9 g/dL) in acute upper GI bleeding
Variceal bleedingRestrictive transfusion is particularly important — overtransfusion increases portal pressures and may worsen variceal bleeding; target Hb 7–8 g/dL
Coagulopathy correctionIn patients on anticoagulants: reverse anticoagulation per agent-specific protocols; FFP or PCC for warfarin; idarucizumab for dabigatran; andexanet alfa or PCC for factor Xa inhibitors
Platelet transfusionTransfuse if platelet count < 50,000/μL with active bleeding
Proton pump inhibitorHigh-dose PPI (esomeprazole or pantoprazole 80 mg IV bolus + 8 mg/h infusion) for suspected peptic ulcer hemorrhage (post-endoscopic confirmation)

6. MTP Deactivation Criteria

The MTP should be deactivated when the following criteria are met:

CriterionDetails
Hemorrhage controlledSurgical, endoscopic, or interventional hemorrhage control achieved; no ongoing active bleeding
Hemodynamic stability restoredSBP > 100 mmHg (or patient’s baseline); MAP > 65 mmHg without escalating vasopressor doses; heart rate < 100 bpm
Metabolic parameters improvingLactate trending downward; base deficit improving; pH > 7.25 and trending toward normal
Laboratory values stabilizingHemoglobin stable without ongoing transfusion; platelets > 50,000/μL; INR < 1.5; Fibrinogen > 150 mg/dL; ionized calcium ≥ 1.1 mmol/L
Clinical assessmentAttending physician/trauma team leader determines that massive hemorrhage phase has concluded

Process: Communicate MTP deactivation to the blood bank clearly and promptly. Return all unused blood products to the blood bank. Transition to standard (non-MTP) ordering for any ongoing transfusion needs.


References


  1. 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 ↩︎ ↩︎

  2. 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 ↩︎ ↩︎

  3. 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 ↩︎ ↩︎

  4. Whiting P, Al M, Westwood M, et al. “Viscoelastic Point-of-Care Testing to Assist with the Diagnosis, Management and Monitoring of Haemostasis: A Systematic Review and Cost-Effectiveness Analysis.” Health Technol Assess. 2015;19(58):1-228. DOI: 10.3310/hta19580 ↩︎ ↩︎

  5. Holcomb JB, Jenkins D, Rhee P, et al. “Damage Control Resuscitation: Directly Addressing the Early Coagulopathy of Trauma.” J Trauma. 2007;62(2):307-310. DOI: 10.1097/TA.0b013e3180324124 ↩︎

  6. Bickell WH, Wall MJ Jr, Pepe PE, et al. “Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Torso Injuries.” N Engl J Med. 1994;331(17):1105-1109. DOI: 10.1056/NEJM199410273311701 ↩︎

  7. 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. DOI: 10.1016/S0140-6736(10)60835-5 ↩︎

  8. 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. DOI: 10.1016/S0140-6736(17)30638-4 ↩︎ ↩︎ ↩︎

  9. 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 ↩︎

  10. Villanueva C, Colomo A, Bosch A, et al. “Transfusion Strategies for Acute Upper Gastrointestinal Bleeding.” N Engl J Med. 2013;368(1):11-21. DOI: 10.1056/NEJMoa1211801 ↩︎