Holley Transfusion and Coagulopathy 130902114337 Phpapp01

8/17/2019 Holley Transfusion and Coagulopathy 130902114337 Phpapp01

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Transfusion andTransfusion andCoagulopathyCoagulopathy

Anthony Holley

Intensivist

Royal Brisbane & Women’s Hospital


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ExsanguinationExsanguination

Haemorrhage remains a major and

potentially reversible cause of all trauma

deaths.

More pronounced in the setting ofpenetrating trauma.

Mortality in this group is 20-50%


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Rev Gonsky

@coolholdenv8R


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The MissionThe Mission


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n arrival in !"n arrival in !"

#room H$ 2&' () *+,0' !tensivepelvic . INR 1.3

(ride H$ 00' () 0+*0' bilateral femur

fractures. INR1.2 "river H$ /0' () *0+&5' pelvic '

moderate severity head injury' bilateral

tib+b compound . INR1.7 1ront passenger H$ 00 () *0+/,' 134T.

INR 1.1


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oagulopathy is present atoagulopathy is present at

admission in 25% of traumaadmission in 25% of trauma

patients.patients.

3ssociated 6ith a 5-fold increase3ssociated 6ith a 5-fold increase

in mortality.in mortality.


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Early coagulopathy in trauma patients: anEarly coagulopathy in trauma patients: an

on-scene and hospital admission study.on-scene and hospital admission study.

Prospective, observational study

investigating the on-scene coagulation

profile and its time course. N = 45 patients

At the scene of the accident, before fluid

administration. to hypoperfusion.


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MeasuredMeasured

Prothrombin time

Activated partial thromboplastin time

ibrinogen concentration

actors !!, " and "!! activity,

ibrin degradation products

Antithrombin and protein # activities

Platelet counts and base deficit.


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$n-scene coagulation status %as abnormal

in 5&' of patients.

Protein # activities %ere decreased

actor " levels decreased significantly

%ith the severity of the trauma.


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Why?Why?


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Acute Coagulopathy of Trauma Acute Coagulopathy of Trauma

4yndrome of non-surgical bleeding from mucosallesions' serosal surfaces' 6ound and vascular accesssites associated 6ith serious injury

78$ 9 .5 reliably predicts those 6ho 6ill re:uire

massive transfusion 4een in most severely injured upon admission to !"

◦ oagulopathy correlates 6ith 744 3lso associated 6ith;

◦ Hypothermia ◦ 3cidosis


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A Time to Consider A Time to Consider

Mechanism of coagulopathy

4trategies to best manage patients

(est modality to assess coagulopathy


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Coagulopathy

Acidosis Hypothermia

Bleeding

Kashuk JL, Moore EE, Millikan JS, Moore JB. Major abdominal vascular

trauma—a unified approach. J rauma !"#$% $$&'($)'(".

Classically Trauma-induced

Coagulopathy


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Time to Challenge theTime to Challenge the

Dogma?Dogma?

@8one of these appears to be responsible for

acute coagulopathy' and it appears thatshocA is the prime initiator of the processBC

@Trauma-induced coagulopathy can develop in2/./% of patients independent of acidosis and

hypothermia but secondary to trauma by itselfD

E J Trauma' 3ug 0*' p2?2


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Coagulopathy

Acidosis Hypothermia

Bleeding

I

n j

u r y

Hy p er f i b r i nol y si

Classically Trauma-induced

Coagulopathy

AP C


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Dilution?Dilution?

Fittle or no dilutional effect of crystalloid therapy on

the standard tests of coagulation either in vitro or in

healthy volunteers

Fondon study G median uid 500 ml

#erman study G median uid 2.2 F

olloid vs rystalloid

oagulopathy 6as present in 0% of patients 6horeceived less than 500 ml of uid

I 3lternative mechanism


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Moderate+severe hypothermia present = J% of trauma

patients

$elationship bet6een hypothermia' shocA and injury

severity a 6eaA independent predictor of mortality

Kery little effect of moderate hypothermia on coagulation

proteases.

4ignicant effects on function and clinical bleeding only at

temperatures = &&L.

Hypothermia?


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!ffects of 7K HF acid on human volunteers. "enite doseEresponse of acidaemia on clotting function

by thromboelastometry. Fittle clinically signicant effect on protease function do6n

to a pH of ?.2 in in-vitro studies 3nimal studies; pH of ?. produces only a 20%

prolongation of the )T 3)TT.

Acidaemia?


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onsumption regarded as a primary cause of traumaticcoagulopathy

Fittle evidence for consumption of clotting factors as a

relevant mechanism 7n patients without shocA coagulation times are never

prolonged' regardless of the amount of thrombin generated

Consumption?


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4hocA and systemic hypoperfusionI "ose-dependent prolongation of clotting

times 6ith increasing systemichypoperfusion. (ase decit


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3cute coagulopathy in massive transfusion

appears to be due to activation ofanticoagulant and brinolytic path6ays. ThrombomodulinEprotein path6ay is

implicated.

Mechanism of Acute

Traumatic Coagulopathy


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Normal

Haemostasis

Procoagulant

Activity

Antifibrinolyticactivity

AnticoagulantActivity

fibrinolytic

activity

Thrombus

Bleeding


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Nith tissue hypoperfusion the endotheliumepresses thrombomodulin 6hich complees

6ith thrombin. Fess thrombin is available to cleave brinogen Thrombin compleed to thrombomodulin

activates protein ' 6hich inhibits cofactors K

and K777

rotein C Activation


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rotein C Anticoagulant ath!ayrotein C Anticoagulant ath!ay


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.

Brohi et al. Acute traumatic coagulopathy: initiated by hypoperfusion:

modulated through the protein C pathway? Ann Surg 2007 May. 2007

May;2!"!#$8%2&8'

http://www.ncbi.nlm.nih.gov/pubmed/17457176http://www.ncbi.nlm.nih.gov/pubmed/17457176


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"iological #esponse athological"iological #esponse athological

in $hoc%in $hoc%

Tissues subjected to lo6-o6 states

generate an anticoagulant milieu

3voids thrombosis of vascular beds.


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Trauma is associated 6ith increasedbrinolytic activity.

Tissue plasminogen activator is releasedfrom the endothelium follo6ing injury andischaemia.

Focal control mechanism to reduce

propagation of clot to normal vasculature

Hyperfi&rinolysis


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Hyperfi&rinolysisHyperfi&rinolysis

Reduction in plasminogen activator inhibitor-1 (AI-1! levels

in tissue hypoper"usion

APC


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CRASH-2 trial collaborators. The Lancet. 2010;376:23-32

Effects of tranexamic acid on death'vascular occlusive events' and &lood

transfusion in trauma patients !ith

significant haemorrhage (C#A$H-)*+ a

randomised' place&o-controlled trial

rane*amic acid


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A()M ASM 20%0

Plasminoge

n activator

PlasminPlasminoge

n

Blockade (locAade

Traneamic AcidTraneamic AcidTraneamic AcidTraneamic Acid

! i b r i n

o l y

s i s


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The $tudyThe $tudy

)rospective double blind 2?/ hospitals /0 countries nO202 Traneamic acid vs placebo

g over 0 minutes then g over * hours )rimary outcome; in hospital four 6eeA

mortality


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Tranexamic AcidTranexamic Acid


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Tranexamic AcidTranexamic Acid


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"ut,,,,,,,,,,,,"ut,,,,,,,,,,,,

!ntrance criteria soft


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Arch Surg. 2012;147(2):113-119. 2011

Study profi le illustrating the overall cohort and study groups.

MATTERs

MATTER


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Arch Surg. 2012;147(2):113-119.2011

MATTERs

MATTER


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From: Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study

Arch Surg. 2012;147(2):113-119.

Percentage of patients with hypocoagulopathy on admission to the emergency department (ED) and then the intensive care unit(ICU) following the initial operation. Coagulation data were available for 462 patients in the overall cohort and 155 patients in thegroups that received massive transfusion. TXA indicates tranexamic acid. * P < .05.

MATTERs

MATTERs


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Arch Surg. 2012;147(2):113-119.

Kaplan-Meier survival curve of the overall cohort, including patients receiving tranexamic acid (TXA) vs no TXA. P = .006, Mantel-Cox log-rank test.

MATTERs

MATTERs


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From: Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study

Arch Surg. 2012;147(2):113-119.

Kaplan-Meier survival curve of the massive transfusion group receiving tranexamic acid (TXA) or no TXA. P = .004, Mantel-Cox log-rank test.

MATTERs


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Tranexamic acid safely reduces theris% of death in &leeding traumapatients


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The ld Puestion of $atiosIThe ld Puestion of $atiosI


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+olcomb JB, ade -E, Michalek JE, -hisholm B, /ar0abal L1, Schreiber M1, on0ale0 E1,

2omper J, 2erkins J, Spinella 2-, illiams KL, 2ark MS. 3ncreased plasma and platelet to red

blood cell ratios improves outcome in 4''

massivel5 transfused civilian trauma patients. 1nn Sur6 $77#% $4#&44()48# .


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roduct #atiosroduct #atios

Massive data base G 25 000 ,% transfused ./% received massive transfusions Fogistic regression identied the ratio of 11) to )$(

use as an independent predictor of survival. Nith a higher the ratio of 11);)$(' a greater

probability of survival 6as noted. The optimal ratio in this analysis 6as an 11);)$( ratio

of ;& or less.

ei*eira 2, 3naba K, Shulman 3, Salim 1, 9emetriades 9, Bro:n -,

Bro:der , reen 9, ;hee 2. 3mpact of plasma transfusion in massivel5

transfusedtrauma patients. J rauma $77"% ''&'"


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I d l l RBC i i dI d l t l t RBC ti i t d


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n =()*(

Massive transfusion in n = &4)

*+o ,itigate survival -ias' 2! atients /ho died /ithin 0 ,inutes o1arrival /ere ecluded 1ro, analysis3.

4ncreased latelet ratios /ere associated /ith i,roved survival at

2 hours and 50 days " 6 0.00% 1or -oth#

+olcombe and everybody et al. verybody. rauma (/** Aug01*2(

3uppl )

Increased platelet:RBC ratios are associatedIncreased platelet:RBC ratios are associated

with improved survival after massivewith improved survival after massive

transfusiontransfusion

..


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+rau,a. 200;$5!895.


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$etrospective data demonstrate arelationship bet6een higher cumulative

11);)$( ratios and lo6er mortality at a

specic point in time $atio calculated at 2/ hours after

admission in most studies.

3ctual temporal relationship bet6een theadministration of specic components

and mortality has not been elucidated


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htt$::///.n-a.gov.au:guidelines:order:inde.ht,l

htt$::///.n-a.gov.au:guidelines:revie/.ht,l

http://www.nba.gov.au/guidelines/order/index.htmlhttp://www.nba.gov.au/guidelines/order/index.html


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National BloodNational Blood

Athority Athority 200 8ational Health and Medical $esearch ouncil+

3ustralasian 4ociety of (lood Transfusion

Clinical practice guidelines on the use of blood components

8o6 replaced by 8(3;

Patient Blood Management Guidelines: Modules !"

) i bl d M) i bl d M


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)atient blood Management)atient blood Management

#uidelines#uidelines

Patient !lood management aims to im"rove clinicalPatient !lood management aims to im"rove clinical


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g "g "

otcomes !y avoiding nnecessary e#"osre to !loodotcomes !y avoiding nnecessary e#"osre to !lood

com"onentscom"onents

7t includes the three pillars of;7t includes the three pillars of;

. ptimisation of blood

volume and red cell

mass

2. Minimisation of blood

loss

&. ptimisation of the

patientQs tolerance of

anaemia.


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*ales indicative o' critical "hysiologic*ales indicative o' critical "hysiologic

derangement inclde)derangement inclde)

. Temperature = &5L

2. pH = ?.2' base ecess 9 E,' lactate 9 / mmol+F

&. ionised calcium = . mmol+F

/. platelet count = 50 R 0J+F5. )T 9 .5 R normal

,. 78$ 9 .5

?. 3)TT 9 .5 R normal

*. brinogen level = .0 g+F.

Practice Point


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Activated .actor /00Activated .actor /00

"#$ trauma patients were enrolled% $&" blunt' $"( penetrating%


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+aser et al. , -rama. 21 $e"/03)456+aser et al. , -rama. 21 $e"/03)456

$andomiSed prospective trial

5?& patients

8o effect on mortality

8o effect on thrombotic events

Trial stopped early for lacA of efcacyB


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Levi M, Lev5 J+, 1ndersen +=, ruloff 9. Safet5 of recombinant activated

factor >33 in randomi0ed clinical trials. ? En6l J Med $7!7%


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Nhat of the )ost Trauma )eriodNhat of the )ost Trauma )eriod

5% of 6ar casualties from 7ra:+3fghanistandeveloped )!

The more 6e bleed the more 6e clot

The more tissue damage 6e sustain themore 6e clot.

)uggested criteria for acti,ation of .TP


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+he routine use o1 ruate -lood co,onent relace,ent' and

= ? 7.2' te,erature 50(.

iscuss dose /ith hae,atologist:trans1usion secialist

- r


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hank @ou hank @ou

Holley Transfusion and Coagulopathy 130902114337 Phpapp01

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