Transfusion in Trauma

Where we have been and where we are going

Jamie Jones Coleman, MD, FACS

Associate Professor of Surgery

University of Louisville School of Medicine

Disclosures

• None... financially

Disclosures

Temporal Trends in Mortality in the United States, 1969-2013

Jiemin Ma, PhD, MHS; Elizabeth M. Ward, PhD; Rebecca L. Siegel, MPH; Ahmedin Jemal, DVM, PhD

Exsanguination remains

Despite advances in care…

Zero Preventable Deaths

• NASEM Report 2016
• 1/5 trauma deaths preventable
• Approximately 30,000 deaths from hemorrhage/year in the United States

How can we get there?

• Break the cycle
• Lose less, replace better

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Where we started…

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Where we started…

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Where we are

• Damage Control Resuscitation
•    Whole Blood
•    Functional Testing/Guided Resuscitation
• TEG
• ROTEM
•    Adjuncts
• TXA
• PCC

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Damage Control Resuscitation

• Conventional treatment
• Rapid reversal acidosis
• Prevention of hypothermia
• Did not address coagulopathy

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Damage Control Resuscitation: Directly Addressing The Early Coagulopathy of Trauma

Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, Cox ED, Gehrke MJ, Beilman GJ, Schreiber M, Flaherty SF.

2007

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Decrease crystalloid by 50%

Permissive Hypotension

• Patients SBP < 90 mmHg randomized out of hospital
• Controlled Resuscitation
• 250ml if no radial pulse or SBP < 70 mmHg + additional 250 ml to maintain 70 mmHg
• Standard Resuscitation
• 2 liters crystalloid initially + additional fluids to maintain 110 mmHg

• No difference in admission vital signs
• Mean transport time 13 min
• No differences in renal function, mortality at 24 hours
• SAFE

Permissive Hypotension

• 722 Abstracts screened
• Many underpowered
• Pooled Odds Ratio 0.7 (CI 0.53-0.92)
• Overall, suggesting survival benefit
• "May" reduce blood loss, blood utilization

• Median ratio of FFP:PRBC
• 1.17 in survivors
• 1.3 in non-survivors

What about in civilian population?

Too good to be true?

Too good to be true?

• Prospective Observational Multicenter Major Trauma Transfusion
• 10 Level 1 trauma centers
• Primary objective
• Investigate in hospital mortality in all patients surviving at least 30 minutes after ED admission
• Minute to minute tracking until resuscitation complete
• Followed until hospital discharge

• Increased ratios of plasma:RBC and platelets:RBC independently associated with decreased 6-hour mortality
• In the first 6 hours
• Patients with ratio <1:2 were 3-4 times more likely to die than patients with ratio ≥ 1:1

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• After 24 hours, plasma and platelet ratios were unassociated with mortality

Early Plasma and Platelets good…�What ratio?

• Phase III clinical trial
• Plasma:Platelet:pRBC
• 1:1:1 
• 1:1:2
• No difference in 24-hour or 30-day mortality

BUT

• More patients in 1:1:1 group achieved hemostasis and fewer died from exsanguination (9.2% vs 14.6%)

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Best Prehospital fluid?

• 501 patients
• 230 received plasma
• 271 received crystalloid
• Plasma group
• 39% reduction in 30-day mortality
• Lower median prothrombin time

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• COMBAT trial no difference in 28-day mortality
• COMBAT and PAMPer data combined
• Prehospital plasma is associated with a survival benefit when transport times are longer than 20 minutes

Whole Blood

What is old becomes new

Was Aristotle right?

Whole Blood:

500 mL, single WB unit

• Hct: 38-44%
• Plt: 150-400K
• Coags: 100%
• Fibrinogen: 1500mg

Component Therapy:

1U PRBC + 6U PLT + 1U FFP unit + 10 pk Cryo

• Hct: 29%
• Plt: 87K
• Coags: 65%
• Fibrinogen: 750mg

Low Titer Group O Whole Blood

• Form predominantly used in civilian setting
• Contains low levels of antibodies
• Anti-A and Ant-B titers < 256
• Safe to be given without typing and crossmatching recipient
• Decreases exposure donors/unit

From the battlefield…

To the civilian…

• 2015-2016 TQIP
• 8,494 patients identified
• 280 whole blood + component therapy
• 8214 component only

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• Whole blood
• Lower 24-hr mortality
• Lower in-hospital mortality
• Fewer major complications

• Prospective
• WB group – patients who received any whole blood
• Component group
• WB group – Lower BP, lower GCS, lower pH, more coagulopathic on arrival

• Whole blood independently associated with a 4-fold increased survival
• Whole blood patient 60% reduction in overall transfusions

Best prehospital fluid?

• 2017 paper highlighting lessons learned from the Trauma and Hemostasis Oxygenation Research (THOR) meeting
• Norwegian HEMS
• Comprehensive program allowing for cold whole blood pre-hospital since 2015

In the United States

• 2018 Low titer whole blood available prehospital southwest Texas
• Patients who received whole blood
• Greater improvement shock index
• Reduction in early mortality

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Room to grow

No more components?!

The evolving science behind it all

Evolving technology

Thromboelastography               Thromboelastometry

TEG                                                                  ROTEM

Not all components, not all people

“A growing body of evidence suggests this approach may improve survival while reducing volumes of blood products transfused.”

Limitations

• Accuracy operator dependent and there is both a physician and system-based learning curve
• iTACTIC
• No evidence the use of TEG/ROTEM vs PT/PTT/INR improved 28 day mortality
• Lack of patients with significant surgical bleeding
• Difficult to differentiate cause of death (hemorrhagic vs TBI)
• Different experience levels within participating centers
• Different patterns of trauma, different trauma systems

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Adjuncts/

Not just about the blood

TXA

• Tranexamic acid
• Antifibrinolytic
• Binds to plasminogen and blocks the interaction with fibrin
• Prevents dissolution of the fibrin clot

CRASH-2

• “Aim to assess effect of TXA on death in trauma patients with significant hemorrhage.”
• RCT double blind placebo controlled
• 20,211 pts in 274 hospitals in 40 countries
• Adult patients with / at risk of major hemorrhage
• 1 gm over 10 minute loading dose
• 1 gm infusion over 8 hours

• Treatment ≤ 1 hour from injury significantly reduced risk of bleeding death
• >1-3 hour also reduced risk
• >3 hours from injury seemed to increase risk

• 31 studies
• 43,473 patients
• Significant decrease in 30-day mortality
• 24-hr mortality, overall mortality, thromboembolic events unable to be analyzed due to heterogeneity of pooled data

Prothrombin Complex Concentrate

• Initially developed for hemophilia
• Reversal Vitamin-K deficiency induced coagulopathy
• Trauma Induced coagulopathy
• Compared to FFP
• No blood group testing/matching
• No thawing
• More effective in rapid reduction of INR
• Less volume
• Concerns regarding increased VTE events

• PCC as adjunct to FFP led to improved survival and reduction in transfusion requirements

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• PCC + WB reduction in transfusion requirements compared with WB alone

More studies needed

• Data are limited
• Recommendations vary by country

More of what we know…

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2007

More of what we know…

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2007

More of what we don't know

• Huge area of research growth
• 2021: 1040 papers using "trauma transfusion" as search term on pubmed.gov
• 2022: 671
• CRYOSTAT 2 about to complete enrollment  

A LOT more....

• Who needs blood and when?
• Freeze-dried plasma
• TXA – including subcutaneous
• PCC
• Age of products
• Adaptation of current assays
• AI and computational modeling for prediction medicine

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Especially here…

• Discovering and identifying phenotypes
• Interruptors of disruption, inflammatory mediators  

Thank you

• Jamie.Coleman@Louisville.edu
• Twitter: @jjcolemanmd