Coagulopathy and Goal Directed Hemostatic Resuscitation in Pediatric

Trauma

Adam M. Vogel, MD Assistant Professor, Division of Pediatric Surgery

Washington University in St. Louis School of Medicine December 3, 2013

Disclosure

I have no relevant financial or nonfinancial relationships to disclose

Outline

Acute coagulopathy of trauma TEG

Mechanics Interpretation

TEG in adults trauma TEG in pediatric trauma SLCH

Acute Coagulopathy of Trauma

Acute Coagulopathy of Trauma Multifactorial coagulopathy associated with severely

injured patients

Distinct from: dilutional coagulopathy transfusion related coagulopathy

Related to: Tissue factor release Protein C activation Hypoperfusion Hyperfibrinolysis

3287 patients, 391 patients transfused Acute coagulopathy (INR > 1.5) on arrival: 38% Mortality (+) coagulopathy 24% (vs. 4%)

Retrospective study 1,088 patients PT, aPTT, thrombin time >1.5 times nL

On admission, 24.4 % (+) coagulopathic

Coagulopathy: higher mortality (46% vs. 11%)

211 patients receiving MTP or TEP Prevalence of coagulopathy 70% (INR>1.5)

Mortality in non-coagulopathic 42% Mortality in coagulopathic 67%

N=23,506 2000-2006

In Children . . .

Retrospective review, children < 18y

2002-2009; 744 patients Coagulopathy: INR >1.5

Retrospective review 102 trauma patients

requiring a blood transfusion

Coagulopathic PT > 15.9 s PTT > 42.1 s Fibrinogen < 180 mg/dl Platelets < 185

We therefore conclude . . .

Acute coagulopathy of trauma is real and is BAD

Goal Directed Resuscitation Restore normal physiology Reversal of the shock state

End Organ Perfusion

Mental status, capillary refill, urine output Vital signs

HR, BP, MAP, RR, SaO2 Laboratory data

ABG base deficit, lactate Real-time imaging

FAST-ECHO, IVC filling

Goal Directed Hemostatic Resuscitation

Conventional coagulation tests (CCT) PT/INR PTT Platelet count Fibrinogen D-dimers

Thrombelastography TEG

Assesses global function of clotting proteins, platelets, and the fibrinolytic system

Viscioelastic mechanical properties of blood Useful point-of-care assay

Different devices: TEG vs. ROTEM

Different names for the parameters

Multiple flavors of activating agents: Celite Kaolin Tissue factor Rapid: Kaolin + tissue factor

How It Works Cup oscillates Pin is attached to a torsion

wire Clot binds pin to cup Degree of pin movement

is a function of clot kinetics

Magnitude of pin motion is a function of the mechanical properties of the clot

System generates a hemostasis profile

From initial formation to lysis

PresenterPresentation NotesThe TEG analyzer has a sample cup that constantly oscillates at a set speed through an arc of 445; each oscillation lasts ten seconds. A whole blood sample of 360 l is placed into the cup, and a stationary pin attached to a torsion wire is immersed in the blood. When fibrin first forms, it begins to bind the cup and pin, causing the pin to oscillate in phase with the cup. The degree of pin movement is a function of the kinetics of clot development.

The torque of the rotating cup is transmitted to the immersed pin only after fibrin or fibrin-platelet bonding has linked the cup and pin together. The strength of these fibrin-platelet bonds affects the magnitude of the pin motion.

The magnitude of the output is directly related to the strength of the forming clot. As the clot retracts or lyses, the bonds between the cup and pin are broken, and the transfer of cup motion is diminished. The movement of the pin is converted by a mechanical-electrical transducer into an electrical signal, which can be monitored by a computer.

The movement of the pin generates a hemostasis profile, which is a measure of the time it takes for the first fibrin strand to form, the kinetics of clot formation, the strength of the clot (in shear elasticity units of dyn/cm2), and the dissolution of clot.

R value or ACT: time to initial clot formation K time time for tracing to reach 20mm angle: rate of clot formation Maximum amplitude (MA): clot strength LY30: percent amplitude reduction in 30 minutes

PresenterPresentation NotesThis is an example of a TEG tracing showing both coagulation and fibrinolysis . . .

The R value or ACT in rTEG is the time to initiate clot formation, and is thought to reflect clotting factors. Normal range, 0-118 seconds

The K time is the time for the tracing to reach 20mm. Normal range, 1-2 minutes.

The alpha angle represents the rate of clot formation. Normal range, 66-82 degrees.

Both k and alpha are thought to reflect fibrinogen

The MA or maximum amplitude represents maximal clot strength and is thought to reflect platelet function. Normal range, 54-72 millimeters.

Finally, the LY30 is the percent degradation of the tracing formthe MA over 30 min and reflects fibrinolysis. Normal range, 0.0-7.5%.

Normal TEG Tracing

Hemorrhagic TEG Tracing

Monitoring Hemostasis

Need whole blood sample TEG analysis uses whole blood CCT and platelet counts use plasma

Measure interaction of components TEG analysis reflects interaction CCT and platelet counts isolate components

Measure dynamic changes from start to finish of process TEG analysis reflects dynamic changes CCT and platelet counts reflect one point in time

PresenterPresentation NotesMonitoring hemostasis using the cell-based model requires a whole blood test, as in TEG analysis. Whole blood is needed to measure the interactions among platelets, coagulation factors, and other cellular or plasmatic factors. Many laboratory tests including PT, aPTT, TT, D-DIMER, and platelet counts use plasma, and as a result miss the impact of the cellular elements.

TEG analysis reflects the cell based model and extends beyond it by measuring the net effect of all the blood-borne components of hemostasis. These include coagulation factors, fibrinogen, platelets, fibrinolytic factors, inflammatory cells, blood cells, mediators and most pharmacological agents.

The hemostatic process is dynamic, and the components interact differently as the process moves from activation to clot formation to clot lysis. Monitoring should reflect the dynamic changes of all components from start to finish, as in TEG analysis. Most tests like PT, aPTT, TT, and platelet count focus on just one component at a specific, isolated point in the process.

TEG in Adult Trauma

Prospective, observational N=300 ATC: PT > 1.2 Low CA (MA in ROTEM) at 5 min < 35

Likelihood of PRBC and FFP Likelihood of MTP

Prospective, TBI by CT N= 69; TEG and CCT Hypocoagulability

TEG (R

Prospective data collection > 6 units PRBC within 6 hours of admission Pre-rTEG (N=34) and post-rTEG(N=34)

Trend towards fewer products in the post-rTEG Improved lower FFP:PRBC in the post-rTEG Improved mortality 65% to 29%

Small N, ISS differences

20 patients rTEG, kTEG, CCT Time to results (MA)

rTEG: 19.2 3.1 min kTEG: 29.9 4.3 min CCT: 34.1 14.5 min

rTEG is the fastest

rTEG and kTEG

Prospective data collection 10/2009 2/2010 272 major trauma activations rTEG: kaolin + tissue factor CCT: PT, aPTT

Timing: specimen clocked-in to results Early rTEG values (ACT, K,): 5 min Late rTEG values (, MA): 15 min CCT: 48 min p < 0.001

Transfusions ACT > 128 s (first to result) predicts PRBC, plasma, platelet,

and MTP ACT < 105 s identifies patients who did not receive a

transfusion

Prospective, 9/2009-2/2011 N=1974

Multiple linear regression controlling for age,

gender, mechanism w-RTS, ISS, and base deficit

ACT predicted patients with substantial bleeding and RBC transfusion better than PT/PTT or INR (p = 0.03)

-angle was superior to fibrinogen for predicting plasma transfusion (p < 0.001)

mA was superior to platelet count for predicting platelet transfusion (p < 0.001)

Can TEG replace CCTs?

These correlations improved for transfused, shocked or head injured patients

The charge for r-TEG ($317) was similar to the five CCTs (>$400)

Admission conventional coagulation tests can be

replaced with r-TEG

Can TEG replace CCTs?

TXA: antifibrynolytic agent Randomized, prospective, blinded, placebo-

controlled in 40 countries, 274 hospitals Adult trauma pts with hemorrhage < 8hrs from

injury w/: SBP < 90, HR > 110 or at risk TXA (N=10060) vs placebo (N=10067) TXA reduced mortality

TEG in Pediatric Trauma

5yM s/p peds v. auto CHI, pulmonary contusion Grade IV liver w/ Hepatic artery injury Damage control laparotomy: packing Interventional radiology Serial TEGs, goal directed therapy (w/ factor VII)

rTEG in Pediatric Trauma Retrospective

January 1, 2007 July 31, 2011

Pediatric code III trauma activations

Age 14 years Pediatric level I trauma center Admission rTEG

PresenterPresentation NotesThis was a retrospective review over a two year period of the highest level trauma activations at an ACS verified level 1 pediatric trauma center of patients that received an admission rTEG

Methods Demographic, clinical, outcome data

Transfusions (6 hours) Life saving interventions (6 hours)

Endotracheal intubation Bedside surgical procedure (ICPm, CT, CVL) Emergent surgical procedure

Statistical analysis Spearmans correlation Multivariate analysis (age, gender, ISS)

PresenterPresentation NotesDemographic, clinical, and outcome data were extracted from the patients electronic medical record and trauma registry and data relating to transfusion requirement and life saving interventions were obtained.

Spearmans correlation was used to relate rTEG parameters to conventional coagulation tests .

Multivariate analysis controlling apriori for age, gender, and ISS was performed top evaluate rTEG parameters with transfusion requirements and life saving interventions.

Demographics Number of patients 86

Male gender, % 67%

Median age in years (IQR) 8 (3, 12)

Blunt mechanism of injury, % 88%

Median scene GCS (IQR) 9 (3, 15)

Median EC GCS (IQR) 3 (3, 15)

Median Injury Severity Score, ISS, (IQR) 21 (9, 33)

30-day survival, (%) 88%

PresenterPresentation NotesPatient demographics are as follows:For background, over the 2 year period, there were 2955 pediatric trauma activations, 326 were classified as code 3, and 86 of these patents received an rTEG on admission.

The majority were male and the predominant mechanism was blunt. The median ISS was 21.

There was an 88% survival.

TBI Head AIS >3 was 55%

rTEG and CCT ACT k-time -angle MA

aPTT r=0.68

p

Early Transfusion

Controlling for age, gender, ISS

ACT, R, K, , and MA Predict PRBC and FFP transfusion

Life Saving Interventions

Only MA predicted life saving interventions OR 0.84; 95% CI 0.72-0.98; p=0.032

Limitations

Single center

Retrospective

Sample size

PresenterPresentation NotesThis study has several limitations most notably its retrospective nature, its single center and small sample size.

Conclusions

rTEG correlates with conventional coagulation tests

rTEG predicts transfusion requirements

rTEG predicts life saving interventions

GOAL DIRECTED HEMOSTATIC RESUSCITATION

PresenterPresentation NotesDespite these limitations, we conclude the rapid thromboelastography may be very useful in pediatric trauma.

rTEG values do correlate with conventional coagulation tests

It also predicts the need for transfusion and other life saving interventions.

Rapid thromboelastography may be a valuable tool in pediatric trauma and may serve as a guide for goal directed hemostatic resuscitation.

A word (or two) on Massive Transfusion

Here at Childrens . . .

Goal Directed Hemostatic Resuscitation at SLCH

TEG provides rapid, valuable, actionable data on hemostasis and coagulopathy

The goal for goal directed therapy Massive Transfusion Protocol

Add TEG to admission labs for patients identified at

risk for bleeding/coagulopathy GCS/TBI Penetrating trauma (t-shirt and boxer shorts) Massive transfusion protocol

Thank you

Coagulopathy and Goal Directed Hemostatic Resuscitation in Pediatric TraumaDisclosureOutlineAcute Coagulopathy of TraumaSlide Number 5Slide Number 6Slide Number 7Acute Coagulopathy of TraumaSlide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13In Children . . .Slide Number 15Slide Number 16We therefore conclude . . .Goal Directed ResuscitationGoal Directed Hemostatic ResuscitationSlide Number 20ThrombelastographyHow It WorksSlide Number 23Normal TEG TracingSlide Number 25Hemorrhagic TEG TracingMonitoring HemostasisTEG in Adult TraumaSlide Number 29Slide Number 30Slide Number 31Slide Number 32rTEG and kTEGSlide Number 34Slide Number 35Slide Number 36Can TEG replace CCTs?Can TEG replace CCTs?Slide Number 39TEG in Pediatric TraumaSlide Number 41Slide Number 42rTEG in Pediatric TraumaMethodsDemographicsrTEG and CCTEarly TransfusionLife Saving InterventionsLimitationsConclusionsSlide Number 51A word (or two) on Massive TransfusionSlide Number 53Slide Number 54Here at Childrens . . .Goal Directed Hemostatic Resuscitation at SLCHThank you