Massive Transfusion in Surgical Patients — MTP Triggers, Balanced 1:1:1 Ratios, TXA Timing, Fibrinogen, Calcium and Whole Blood

Blunt polytrauma, systolic pressure 78, heart rate 128, pelvis unstable, FAST positive, second unit of red cells running and the laboratory still processing. Do you activate now or wait for numbers — and when the blood arrives, plasma first or red cells first, how much TXA and by when, fibrinogen for everyone or for the hypofibrinogenaemic, and how much calcium with it? The examiner will watch you trigger by score, sequence by PROPPR, time TXA by CRASH-2, ration fibrinogen by CRYOSTAT-2, and defend calcium by citrate arithmetic. This page teaches all five moves with every number taken from the papers named beside it.^[6][1][2]

Overview & Definition — the MTP patient and the balanced-ratio idea

The MTP patient is defined by physiology plus activation, not by a unit count: injured adults requiring activation of the hospital major hemorrhage protocol with evidence of active hemorrhage, systolic pressure below 90 at any time, and at least 1 unit of blood component already transfused — the CRYOSTAT-2 entry population.^[10] The paediatric line examiners accept is explicit: infusion of 40 mL/kg of blood products in the first 24 hours of admission defines massive transfusion in children.^[7] No single universal adult unit threshold is quoted here because the verified trials enrol by activation and physiology — state the gap rather than inventing a number.

The balanced-resuscitation idea predates its proof: prior to 2015, studies supported the benefits of a balanced transfusion ratio, which was then confirmed by the PROPPR randomized controlled trial.^[8] Current massive transfusion protocols should utilize between 1:1:1 and 1:1:2 ratios of the 3 main products — plasma, platelets, and red blood cells.^[8] And speed is a therapy in itself: the shorter the time to blood product delivery the better the outcomes, with products ready in the trauma bay on arrival and faster replacement tied to better resuscitation.^[8]

Classification — three resuscitation strategies, one haemostasis goal

^{[1] [8] [19]}

Each strategy serves haemostasis, not a laboratory value — ratios buy time to surgical control, and the operation, not the bag, stops the bleeding.^[1][22]

Epidemiology & Risk Factors — the denominators that frame every decision

PROPPR enrolled a pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.^[1] CRASH-2 randomised 20 211 adult trauma patients with, or at risk of, significant bleeding across 274 hospitals in 40 countries.^[2] CRYOSTAT-2 randomised 1604 eligible major-haemorrhage-protocol patients (799 cryoprecipitate plus standard care versus 805 standard care) with median Injury Severity Score 29, over a third penetrating, and a third hypotensive on arrival.^[10]

The paediatric denominator is stark: 39 of 2035 paediatric trauma patients (1.9%) met massive-transfusion criteria — and all-cause mortality in those children was 49% (19 of 39) versus 0.01% (20 of 1996) in the rest.^[7] The whole-blood evidence base is large but observational: 24 studies with 58 717 subjects (5164 receiving low-titre O whole blood) in one meta-analysis, and 34 476 TQIP patients (9023 whole blood, 25 453 component) in the selection analysis.^[17][19] The Cochrane ceiling covers 18 randomised trials with 5041 participants across all transfusion strategies.^[13]

Pathophysiology — fibrinogen first, citrate-calcium second, dilution third

Hypofibrinogenaemia is the mechanistic anchor: in severely injured trauma patients, hypofibrinogenaemia is associated with increased mortality, which is why early fibrinogen replacement was hypothesised to save lives.^[11] That hypothesis then failed its two empirical tests: CRYOSTAT-2 added 3 pools of cryoprecipitate (6-g fibrinogen equivalent) within 90 minutes of randomisation and 3 hours of injury with no mortality gain, and the 5-trial meta-analysis found 24% versus 25% mortality with early replacement.^[10][11]

Citrate is the second mechanism every MTP runner must narrate: citrated plasma and components chelate calcium, prehospital plasma recipients show significantly more hypocalcaemia than controls (53% versus 36%), and severe hypocalcaemia tracks decreased survival and massive transfusion.^[14] But citrate is not the whole story — mean arrival ionised calcium sits at 1.08 overall and 1.07 without any prehospital transfusion, so shock itself depletes calcium and arrival hypocalcaemia is common regardless of transfusion.^[16] Transfused patients run only 0.03 lower on arrival: these findings question the paradigm of citrate-induced hypocalcaemia alone in trauma.^[16]

Dilution is the third mechanism and the surgeon's own error: aggressive crystalloid worsens coagulopathy, which is exactly why permissive hypotension with limited fluids reduced complications (respiratory, organ failure and DIC events all fell) and cut in-hospital death in the verified review.^[24] The DIC-shutdown phase belongs to the sibling topic — this topic owns bleeding-phase replacement, and the boundary between them is the haemostasis line.^[24]

Clinical Presentation — the bleeding surgical patient who needs blood now

The MTP candidate declares through physiology: active hemorrhage with systolic pressure below 90 at any time and blood already transfusing — activate on that picture, not on the pending laboratory panel.^[10] In children the trigger pair is quantified: systolic pressure below 100 with shock index above 1.4 identifies massive-transfusion need with 94% combined specificity.^[7] In adults, shock index and pulse pressure characterise MTP patients from prehospital vitals — but the verified adult cutoffs live inside the scoring systems of the next section, so quote the paediatric numbers as numbers and the adult pattern as pattern.^[6][7]

^{[10] [1] [2] [11] [8] [14] [6] [21]}

Differential Diagnosis — coagulopathic versus mechanical versus dilutional bleeding

^{[11] [10] [24] [9]}

Name the category aloud before ordering blood — the viva rewards the candidate who separates what transfusion fixes from what only the operation fixes.^[8][9]

Clinical & Bedside Assessment — scores that trigger activation

The scores review sets the field: 45 articles were eligible for analysis, with 11 validated and four unvalidated scores and tools for predicting MTP activation.^[6] Of those, the Trauma Associated Severe Hemorrhage score is most well validated and discriminates better than the Assessment of Blood Consumption and Prince of Wales scores.^[6] Without laboratory results, the Assessment of Blood Consumption score balances accuracy with ease of use — the score for the bedside without bloods.^[6] The Shock Index uses clinical assessment only with fair performance: a trigger that never rules out.^[6]

Practical activation for the adult bay: combine mechanism, physiology (hypotension, tachycardia, shock index), obvious bleeding and FAST with a validated score where available — TASH where calculable, ABC without laboratories, shock index at the bedside — and transfuse while the score is still being tallied.^[6][8]

Investigations — gases, calcium, fibrinogen and the honest VHA position

Draw gases for shock depth, ionised calcium with every round, fibrinogen early, and a full blood count with coagulation studies — but never let the laboratory gate the blood. Hypocalcemia was defined as ionised calcium of 1.0 or less in the prehospital-plasma analysis, the threshold at which survival associations were measured.^[14] Arrival calcium near 1.08 is already borderline-low in most major trauma with or without transfusion, so a first level below 1.0 is common, expected, and actionable.^[16]

State the viscoelastic position honestly, because the examiner will probe it: of 7743 records screened, ten studies (two randomised, eight observational) compared VHA-guided to control resuscitation — and most found no significant differences in red-cell, plasma, platelet, cryoprecipitate or mortality amounts between groups.^[12] Cochrane agrees at low certainty: there may be little or no 24-hour mortality difference between VHA and conventional tests (RR 0.85), and overall there was little to no evidence of mortality or thromboembolic difference between transfusion strategies.^[13] Use viscoelastic testing as an adjunct for fibrinogen and goal direction where available — never as a gate that delays blood, and never quote a trigger cutoff from this set, because none is verified here.

Management — Ratios: PROPPR 1:1:1 versus 1:1:2 and what each number owns

PROPPR randomised blood product ratios of 1:1:1 (338 patients) versus 1:1:2 (342 patients) during active resuscitation plus all local standard care.^[1] No significant mortality difference resulted at 24 hours (12.7% versus 17.0%) or at 30 days (22.4% versus 26.1%).^[1] But the cause-of-death analysis is the viva answer: exsanguination, the predominant early killer, fell significantly with 1:1:1 (9.2% versus 14.6%), and more patients achieved haemostasis (86% versus 78%).^[1] The price was modest and safe: more plasma (median 7 versus 5 units) and platelets (12 versus 6 units) with similar red cells (9 units), and no difference across 23 prespecified complications including ARDS, organ failure, VTE, sepsis and transfusion reactions.^[1]

The dynamic analysis refines when ratios matter most: where haemostasis took longer than 2 hours, 1:1:1 carried higher haemostasis probability from hour 4 on — with dual-high plasma and platelet ratios carrying 2.49-fold haemostasis likelihood in hour 3 — so receiving higher ratios hastens haemostasis in patients still bleeding at 3 hours.^[22] Sequence matters too: across 50 580 TQIP massive-transfusion patients (13 818 plasma-first), a red-cell-first approach carried independently worse adjusted 6-hour, 24-hour and in-hospital mortality — modest in magnitude and level III observational, but directionally consistent with giving plasma early.^[25] And the strategy is affordable: per 100 patients, 1:1:1 costs 5.6 versus 5.0 million with eight more haemostases and 218.5 more years of life expectancy at 2994 per year gained.^[23]

Management — Tranexamic acid: CRASH-2 dosing and the timing gradient

Dose CRASH-2 exactly: 1 g loading over 10 minutes then 1 g infusion over 8 hours, randomised within 8 hours of injury — all-cause death 14.5% versus 16.0% (RR 0.91) with bleeding death 4.9% versus 5.7% (RR 0.85).^[2] The authors concluded tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study.^[2]

Then draw the timing gradient, because timing is the entire viva: treatment within 1 hour of injury cut bleeding death (RR 0.68), treatment between 1 and 3 hours still helped (RR 0.79), and treatment after 3 hours carried a harm signal (RR 1.44).^[3] The pooled CRASH-2/3 analysis of 28 448 patients tightens the rule: relative reduction peaks within 2 hours then falls rapidly, the statistically optimal criterion is treatment within 2 hours of injury or with GCS below 9, the largest absolute gains go to hypotensive low-GCS patients treated early, and severe brain injury may retain benefit beyond 2 hours.^[4] Give the loading dose with the first blood — the clock starts at injury, not at arrival.

State the equity finding because examiners now ask it: TXA cut death equally in women (RR 0.69) and men (RR 0.80) with no heterogeneity — yet women received it far less often (7.3% versus 16.8%, OR 0.39).^[5] Audit your own bay: equal benefit demands equal administration.^[5][20]

Management — Fibrinogen: empirical cryoprecipitate fails, targeted replacement stands

CRYOSTAT-2 tested the maximalist hypothesis directly: 3 pools of cryoprecipitate (6-g fibrinogen equivalent) added to standard care within 90 minutes of randomisation and 3 hours of injury, in 1604 major-haemorrhage-protocol patients.^[10] All-cause 28-day mortality was 26.1% standard care versus 25.3% cryoprecipitate (OR 0.96) — no difference — with identical thrombotic events (12.9% versus 12.7%).^[10] The conclusion is the viva sentence: the addition of early and empirical high-dose cryoprecipitate to standard care did not improve 28-day mortality.^[10]

The meta-analysis concurs across 1906 screened studies with 12 included and five randomised trials totalling 1758 participants: early fibrinogen replacement 24% versus control 25% mortality (OR 1.03) — no difference — against the background association that hypofibrinogenaemia tracks death.^[11] The surgical resolution: measure fibrinogen, replace documented hypofibrinogenaemia with bleeding by local protocol, and never protocolise empirical cryoprecipitate for every activation.^[10][11]

Management — Calcium: citrate load, arrival reality and replacement signals

Measure ionised calcium in every MTP round. Prehospital plasma raised hypocalcaemia to 53% versus 36% of controls (adjusted RR 1.48), and severe hypocalcaemia independently predicted decreased survival and massive transfusion.^[14] Arrival hypocalcaemia is nevertheless near-universal: mean 1.08 overall, 1.07 without any prehospital transfusion, transfused patients only 0.03 lower — so replace by level, not by assumption about citrate alone.^[16]

The dosing signal comes from whole-blood resuscitation: of 542 low-titre O whole blood recipients (99 in CPR excluded, 273 analysed), 24-hour mortality was 13.6% — and 1 g or more of calcium chloride per 2 units of whole blood independently cut 24-hour mortality odds by 84% (OR 0.164) on multivariable analysis.^[15] That is a single-centre observational signal, not a randomised dose table — so run calcium with citrated products by ionised levels, recheck after each round, and never let calcium monitoring lapse while plasma and platelets run.^[15][14][16]

Management — Whole blood, hypotension and the first-30-minutes sequence

^{[6] [1] [25] [2] [4] [24] [14] [11]}

Whole blood carries the strongest observational survival signal in the set: low-titre O whole blood associated with improved 24-hour survival (RR 1.07) and late survival (RR 1.05) across 24 studies and 58 717 subjects.^[17] A second meta-analysis of 14 studies found 24-hour mortality OR 0.67 favouring whole blood, with no differences in stay, ventilator days, ARDS, kidney injury or sepsis — benefit without a harm signal in the measured outcomes.^[18] Selection is the nuance: across 34 476 TQIP patients there was no overall adjusted mortality difference (aOR 0.85, p 0.052) — but hypotensive patients benefited, with SBP below 90 at aOR 0.72 and below 70 at aOR 0.64.^[19] Offer whole blood first where available in hypotensive bleeding; where unavailable, reconstituted 1:1:1 remains the verified platform.^[19][1] And state the limit aloud: findings remain observational, necessitating more randomised trials before whole blood becomes mandate.^[18]

Permissive hypotension completes damage control: across 11 studies with 4529 patients, hypotensive resuscitation cut in-hospital mortality (6.3% versus 16.3%) with no prehospital difference — plus fewer respiratory, organ-failure and DIC complications — and in blunt injury cut 24-hour death (3.2% versus 17.7%, adjusted OR 0.17).^[24] Exclude brain injury from hypotensive targets by principle (no verified target sits in this pack — name the gap), and resuscitate generously once haemostasis and brain perfusion demand it.^[24]

Complications & Pitfalls — early PE, over-transfusion fear and the Cochrane ceiling

The early-PE trap — of 87 PROPPR patients (13%) with VTE, pulmonary embolus predominated in the first 72 hours, with plasma transfusion among the early-associated variables.^[21] Start mechanical prophylaxis the moment bleeding allows, convert to pharmacologic prophylaxis on haemostasis, and image the breathless post-transfusion patient rather than attributing everything to the lung injury.^[21]

The over-transfusion fear trap — among 3121 transfused patients, 1 to 3 units carried no excess kidney, lung, infection, arrest, VTE or stroke risk versus no transfusion or 4 to 9 units — and carried less AKI, ARDS and arrest than 10-or-more-unit resuscitation.^[9] Among patients meeting MTP triggers, 1 to 3 units of allogeneic red cells is not associated with worse outcomes — so transfuse suspected shock without apology, then stop when perfusion returns.^[9]

The strategy-superiority trap — Cochrane found little to no mortality or thromboembolic difference between transfusion strategies overall: prehospital plasma uncertain at 24 hours (RR 1.05, very low certainty) and probably no different at 30 days (RR 0.95, moderate certainty), VHA versus conventional tests little or no 24-hour difference.^[13] Present every strategy choice with its certainty label — the examiner rewards calibrated uncertainty over borrowed conviction.^[13]

The empirical-fibrinogen trap — 6 g equivalent to every activation changed nothing at 28 days with identical thrombosis.^[10] The late-TXA trap — RR 1.44 harm signal after 3 hours.^[3] The calcium-blindness trap — citrate load without ionised monitoring.^[14] The viscoelastic-cutoff trap — quoting trigger numbers no verified source supports.^[12]

Prognosis & Disposition — the numbers that set expectations

^{[1] [2] [3] [10] [17] [24] [9]}

Every MTP patient needs ICU-level care with surgical, transfusion-medicine and critical-care input — ward care after major-haemorrhage activation is a failure-to-rescue setup. Modifiers: time to blood, haemostasis delay beyond 2 hours (where 1:1:1 gains most), brain injury (TXA window and pressure targets), calcium trajectory, and VTE vigilance from hour one.^{[8][22][4][14][21]}

Special Populations — surgical contexts that change the emphasis

• Children: 1.9% massive-transfusion rate with 49% mortality — SBP below 100 plus shock index above 1.4 triggers activation at 94% specificity with 98% negative predictive value; weight-based 40 mL/kg definitional line.^[7]
• Women of any age: equal TXA benefit with unequal delivery (OR 0.39) — prescribe by indication, audit by sex; post-haemostasis transfusion volumes run lower in women without mortality difference.^[5][20]
• Traumatic brain injury: TXA benefit may persist beyond 2 hours with GCS below 9 in the optimal criterion — treat early regardless, and exclude brain injury from permissive-hypotension targets by principle (no verified target in this pack).^[4][24]
• Blunt polytrauma: the strongest permissive-hypotension signal (24-hour death 3.2% versus 17.7%) with fewer respiratory and organ-failure complications — hypotensive, limited-volume resuscitation to haemostasis.^[24]
• Penetrating and hypotensive bleeding: the whole-blood-first subgroup — SBP below 90 and below 70 carry the verified benefit signals where logistics allow.^[19]
• Postoperative non-trauma bleeding: no verified MTP-trial numbers sit in this pack for this population — apply trauma-derived ratios and TXA timing by principle, activate early, and name the evidence gap rather than inventing numbers.
• Prehospital plasma recipients: expect hypocalcaemia (53% versus 36%) — pre-alert calcium, measure on arrival, replace under load.^[14]

Evidence, Guidelines & Regional Differences — the five stories and who led them

• The ratios story (North America): pre-2015 balance signals → PROPPR 680-patient 1:1:1 versus 1:1:2 (exsanguination and haemostasis win, mortality tie) → dynamic analysis (delayed haemostasis gains most) → FFP-first sequencing and cost-effectiveness confirmations.^{[8][1][22][25][23]}
• The TXA story (global, UK-led): CRASH-2 20 211-patient dosing platform → 2011 timing gradient (1-hour benefit, 3-hour harm line) → 2025 pooled optimal criterion (2 hours or GCS below 9) → sex-disaggregated equity audit.^[2][3][4][5]
• The fibrinogen story (UK/US/global): hypofibrinogenaemia-mortality association → CRYOSTAT-2 empirical high-dose negative → 5-trial meta-analysis negative → targeted replacement as the surviving practice.^[11][10]
• The calcium story (US/Europe): prehospital-plasma hypocalcaemia signal → whole-blood dosing signal → arrival-calcium meta-analysis reframing citrate as partial cause.^[14][15][16]
• The restraint story (global Cochrane): VHA-guidance equipoise, strategy equipoise, over-transfusion safety, permissive-hypotension benefit in hospital blunt trauma — the ceiling that keeps every claim calibrated.^{[12][13][9][24]}
• Sibling-topic boundary: shock owns pressors and perfusion targets; DIC owns shutdown phenotypes, scores and heparin — this topic owns blood, ratios, TXA, fibrinogen, calcium and triggers. Cite each where it lives.
• Guideline honesty: no NICE or ACS-TQIP threshold table is quoted anywhere here — the mt-guidance angle returned no verifiable source, so this topic argues from trials and reviews only.

Exam Pearls — the one-liners that score

• PROPPR in one breath: 680 patients, 1:1:1 vs 1:1:2 — 24-hour 12.7 vs 17.0 (ns), exsanguination 9.2 vs 14.6, haemostasis 86 vs 78, 23 complications equal.^[1]
• CRASH-2 in one breath: 20 211 patients, 1 g plus 1 g — 14.5 vs 16.0 all-cause, 4.9 vs 5.7 bleeding death.^[2]
• Timing in one breath: 1 hour or less RR 0.68, 1 to 3 hours RR 0.79, after 3 hours RR 1.44 — optimal within 2 hours or GCS below 9.^[3][4]
• Triggers: TASH most validated, ABC without labs, shock index bedside-fair — paediatric SBP-plus-SI 94% specific.^[6][7]
• Fibrinogen: CRYOSTAT-2 25.3 vs 26.1 (ns) — empirical high-dose fails; meta-analysis 24 vs 25 (OR 1.03).^[10][11]
• Calcium: plasma raises hypocalcaemia (53 vs 36%), arrival mean 1.08 regardless, 1 g or more per 2 whole-blood units cuts mortality odds 84%.^[14][16][15]
• Whole blood: RR 1.07 early and 1.05 late survival, OR 0.67 at 24 hours — hypotension selects (below 90 aOR 0.72, below 70 aOR 0.64), RCTs pending.^[17][18][19]
• Restraint: 1 to 3 units equals no transfusion for harm; Cochrane strategy equipoise; permissive hypotension 6.3 vs 16.3 in hospital.^[9][13][24]
• Equity and cost: TXA equal by sex yet OR 0.39 delivery gap; 1:1:1 buys 218.5 life-years per 100 at 2994 each.^[5][23]
• VTE clock: 13% VTE with early PE dominance — prophylaxis from haemostasis, imaging for breathlessness.^[21]

Revision summary

Activate on physiology — TASH most validated, ABC without laboratories, shock index bedside, paediatric SBP-plus-SI 94% specific — and deliver blood fast and balanced between 1:1:1 and 1:1:2, because speed plus ratios beat laboratories waited upon.^[6][7][8] Resuscitate 1:1:1 by PROPPR (24-hour 12.7 vs 17.0 ns, exsanguination 9.2 vs 14.6, haemostasis 86 vs 78, complications equal), favouring 1:1:1 most once haemostasis passes 2 hours, sequencing plasma early, at 2994 per life-year gained.^{[1][22][25][23]} Give TXA 1 g loading plus 1 g over 8 hours within 2 hours (gradient 0.68 within 1 hour, 0.79 to 3 hours, 1.44 harm after; optimal within 2 hours or GCS below 9; equal by sex despite delivery gap).^[2][3][4][5] Replace fibrinogen for documented low-with-bleeding only (CRYOSTAT-2 25.3 vs 26.1 ns; meta-analysis OR 1.03), monitor ionised calcium under citrate load (plasma 53 vs 36% low; arrival 1.08 regardless; 1 g or more per 2 whole-blood units OR 0.164), and offer whole blood first in hypotension as an observational signal awaiting trials (RR 1.07 early survival; below-90 aOR 0.72).^{[10][11][14][16][15][17][19][18]} Restrain wisely: 1 to 3 units carry no excess signal, Cochrane finds strategy equipoise, permissive hypotension wins in hospital blunt trauma (6.3 vs 16.3), and early PE dominates the first 72 hours of VTE risk.^{[9][13][24][21]}

References25ShowHide

1. [1]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.PMID 25647203
2. [2]Shakur H, Roberts I, Bautista R, et al. 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.PMID 20554319
3. [3]Roberts I, Shakur H, Afolabi A, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet, 2011.PMID 21439633
4. [4]Osawa I, Goto T, Roberts I, et al. Tranexamic acid for trauma: optimal timing of administration based on the CRASH-2 and CRASH-3 trials. Br J Surg, 2025.PMID 40277024
5. [5]Nutbeam T, Roberts I, Weekes L, et al. Use of tranexamic acid in major trauma: a sex-disaggregated analysis of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2 and CRASH-3) trials and UK trauma registry (Trauma and Audit Research Network) data. Br J Anaesth, 2022.PMID 35597623
6. [6]Shih AW, Al Khan S, Wang AY, et al. Systematic reviews of scores and predictors to trigger activation of massive transfusion protocols. J Trauma Acute Care Surg, 2019.PMID 31454339
7. [7]Zhu CS, Braverman M, Goddard S, et al. Prehospital shock index and systolic blood pressure are highly specific for pediatric massive transfusion. J Trauma Acute Care Surg, 2021.PMID 33990534
8. [8]Meneses E, Boneva D, McKenney M, et al. Massive transfusion protocol in adult trauma population. Am J Emerg Med, 2020.PMID 33071074
9. [9]Gelbard RB, Griffin RL, Reynolds L, et al. Over-transfusion with blood for suspected hemorrhagic shock is not associated with worse clinical outcomes. Transfusion, 2022.PMID 35753037
10. [10]Davenport R, Curry N, Fox EE, et al. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA, 2023.PMID 37824155
11. [11]Burt T, Guilliam A, Cole E, et al. Effect of early administration of fibrinogen replacement therapy in traumatic haemorrhage: a systematic review and meta-analysis of randomised controlled trials with narrative synthesis of observational studies. Crit Care, 2025.PMID 39875966
12. [12]Zhu Z, Yu Y, Hong K, et al. Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review. World J Emerg Surg, 2022.PMID 36100918
13. [13]Brunskill SJ, Disegna A, Wong H, et al. Blood transfusion strategies for major bleeding in trauma. Cochrane Database Syst Rev, 2025.PMID 40271704
14. [14]Moore HB, Tessmer MT, Moore EE, et al. Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock. J Trauma Acute Care Surg, 2020.PMID 32317575
15. [15]Rajesh A, Barry L, Limon D, et al. Aggressive calcium chloride dosing reduces early mortality in trauma patients receiving whole blood resuscitation. J Trauma Acute Care Surg, 2026.PMID 41995161
16. [16]Rushton TJ, Tian DH, Baron A, et al. Hypocalcaemia upon arrival (HUA) in trauma patients who did and did not receive prehospital blood products: a systematic review and meta-analysis. Eur J Trauma Emerg Surg, 2024.PMID 38319350
17. [17]Morgan KM, Abou Khalil E, Feeney EV, et al. The Efficacy of Low-Titer Group O Whole Blood Compared With Component Therapy in Civilian Trauma Patients: A Meta-Analysis. Crit Care Med, 2024.PMID 38483205
18. [18]Khan MT, Raza FA, Altaf R, et al. Evaluating the safety outcomes of whole blood versus component transfusion in trauma: A meta-analysis of 59,213 patients. Thromb Res, 2025.PMID 41027124
19. [19]Torres CM, Stolarski AE, Kenzik KM, et al. Identifying trauma patients who benefit from whole blood transfusion: An effect decomposition analysis on patient survival. Transfusion, 2025.PMID 40717387
20. [20]McCrum ML, Leroux B, Fang T, et al. Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study. Surgery, 2019.PMID 30871812
21. [21]Myers SP, Brown JB, Leeper CM, et al. Early versus late venous thromboembolism: A secondary analysis of data from the PROPPR trial. Surgery, 2019.PMID 31230842
22. [22]Nguyen M, Pirracchio R, Kornblith LZ, et al. Dynamic impact of transfusion ratios on outcomes in severely injured patients: Targeted machine learning analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios randomized clinical trial. J Trauma Acute Care Surg, 2020.PMID 32520897
23. [23]Callcut RA, Simpson KN, Baraniuk S, et al. Cost-effectiveness evaluation of the PROPPR trial transfusion protocols. Transfusion, 2020.PMID 32358836
24. [24]Indorewala Y, Nasef Y, Jayagopi K, et al. Permissive hypotension in adult trauma: A systematic review of outcomes across clinical settings, injury type, and resuscitation strategies. Am J Emerg Med, 2026.PMID 42030689
25. [25]Hynes AM, Westein RJ, Turner TJ, et al. Fresh frozen plasma-first approach is independently associated with improved survival in severely injured patients undergoing massive transfusion. J Trauma Acute Care Surg, 2026.PMID 42275580