red blood cell / plasma / platelet ratio and massive ... · red blood cell / plasma / platelet...

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Red blood cell / plasma / platelet ratio and massive transfusion protocols

Anne GODIERService d’Anesthésie-Réanimation

Hopital CochinParis

Groupe d’Intérêt en Hémostase Périopératoire

How do I treat massive bleeding?

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Conflicts of interest

LFB

Octapharma

CSL-Behring

Bayer

BMS-Pfizer

Boehringer-Ingelheim

Léo

Sanofi

Acknowledgement

Pr Sophie Susen (Lille)

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1:1:1 ratio

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Coagulopathy

Massive transfusion

Severe traumaPost-partum haemorrhage

Major surgery (cardiac & aortic surgery)Gastrointestinal bleeding

Liver transplantation

Massive bleeding

Mortality

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Trauma-induced coagulopathy

DilutionHypothermiaAcidosis

Fluid loadingShock

Massivebleeding

Coagulopathy

trauma patient

Trauma induced coagulopathy


Massive RBC transfusion

Adapted from Brohi K, Ann Surg 2007*

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Fluid loadingShock

Massivebleeding

Coagulopathy

Acute traumatic coagulopathy

Tissue Injury

trauma patient



Massive RBC transfusion


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Fluid loadingShock

Massivebleeding

Coagulopathy


Tissue Injury

InflammationFibrinolysis

systemicanticoagulation

activated protein C

trauma patient



Massive RBC transfusionplatelet

dysfonction


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Fluid loadingShock

Massivebleeding

Coagulopathy


Tissue Injury

InflammationFibrinolysis

systemicanticoagulation

activated protein C

trauma patient



Massive RBC transfusionplatelet

dysfonction


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o On-scene: TAC = trauma-associated coagulopathy

On-scene injury

Normal20 (44%)

Normal16 (36%)

Early onset of coagulopathy in trauma

Non-overt TAC22 (49%)

TAC3 (7%)

TAC1 (2%)

Non-overt TAC3 (7%)

Normal16 (36%)

TAC5 (11%)

Non-overt TAC15 (33%)

Normal0 (0%)

TAC3 (7%)

Non-overt TAC0 (0%)

On-scene and trauma resuscitation room coagulation status

Floccard B, et al. Injury 2012;43:26–32

Admission

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Reduced Coagulation Factor Activity

FacteurFII FV FVII FIX FX FXI

Jansen JO, J Trauma 2011

Severe trauma patients

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10-15 mL/kg 30 mL/kgFibrinogène g/L +0.4 +1.0II % +16 +41V % +10 +28VII % +11 +38IX % +8 +28X % +15 +37XI % +9 +23XII % +30 +44

Br J Haematol 2004;125:69-73

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10-15 mL/kg 30 mL/kgFibrinogène g/L +0.4 +1.0II % +16 +41V % +10 +28VII % +11 +38IX % +8 +28X % +15 +37XI % +9 +23XII % +30 +44

Br J Haematol 2004;125:69-73

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Plasma

coagulation factors

fibrinogen

1 FFP = 400 mg of fibrinogen

proteins, including immunoglobulins and albumin

volume expansion with high oncotic pressure

Preclinical studies

less pro-inflammatory than artificial colloids

protective effects on endothelial permeability and vascular stability

Pati S. J Trauma 2010; 69 Suppl 1:S55-63.

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Increasing plasma:RBC ratio

Transfusion with high ratio

Ratio = plasma number / RBC number

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246 trauma patients with massive transfusion(>10 RBC)

1:1.4FFP:RBC 1:2.5 mortality

1:8

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246 trauma patients with massive transfusion(>10 RBC)

1:1.4FFP:RBC 1:2.5 mortality

1:8

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Military trauma studies:beneficial effect of high FFP:RBC ratio

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military civilian trauma studies

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Mortality in patients undergoing massive transfusion n=3400

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Mortality in patients undergoing massive transfusion n=3400

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Limitations

retrospective studies (or cohort studies)

missing data

analytical bias

survival bias

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april 2013

Recommendation 26

We recommend the initial administration of plasma [fresh frozen plasma(FFP) or pathogen-inactivated plasma] (Grade 1B) or fibrinogen (Grade 1C)in patients with massive bleeding.

If further plasma is administered, we suggest an optimal plasma:red bloodcell ratio of at least 1:2. (Grade 2C)

Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ,Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R.

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Platelet : RBC ratio?

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The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center

Hess JR, Lindell AL, Stansbury LG, Dutton RP, Scalea TM.Transfusion. 2009;49:34-9

Records of all patients admitted to a large urban trauma center during 2000 through 2006

N=23 000

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Retrospective data regarding platelet transfusion

mortality variation between trauma receiving large amount of platelets copared to small amount

%

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Retrospective data regarding platelet transfusion

low ratios

high ratios

mortality

mortality variation between trauma receiving large amount of platelets copared to small amount

%

%

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april 2013

We recommend that platelets be administered to maintain a platelet count above 50 × 109/l. (Grade 1C)We suggest maintenance of a platelet count above 100 × 109/l in patients with ongoing bleeding and/or TBI. (Grade 2C)

Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ,Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R.

UPDATED GUIDELINES

TEMPORARY VERSION

Increasing platelet:RBC ratio is associated with a mortality decrease

For massive transfusion platelet units must be part of the second transfusion package

Platelets must be transfused with a platelet:RBC ratio between 1:5 and 1:1. This ratio may be close to 1:1

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Increasing ratios is not enough

t

1:1:1

Ratio : a time-dependent variable

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*

Mortality of trauma patients grouped by deficit status

Ratio = FFP / RBC Deficit = RBC - FFP

O

≤2

>6

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Reducing transfusion delay

carefully constructed massive transfusion protocol

local agreement with the blood bank products available as soon as possible healthcare professionals

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Protocol : 10 RBC4 FFP2 platelets

ratio 1:2.5

*

*

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Reducing transfusion delay

carefully constructed massive transfusion protocol

local agreement with the blood bank products available as soon as possible healthcare professionals

which blood products?number?sequence?

transfusion package

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Packs

Godier A, Samama M, Susen S. Curr Opin Anesthesiol 2012

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Packs

Godier A, Samama M, Susen S. Curr Opin Anesthesiol 2012

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Immediate availability of plasma in the 1st pack

Thawing plasma

Freeze-dried plasma thawed AB group plasma stored for immediate availability together with O group RBC

radio wave-based thawing technology

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1:1:1 ratio in blood transfusion: many argues in massive transfusion

non massively transfused patients?

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Mortality in patients undergoing surgery without massive transfusion

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increase in complications

no improvement in survival

in complications as volumes of plasma

number of units of plasma transfused in 12 hours

over

all c

ompl

icat

ions

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over

all c

ompl

icat

ions

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over

all c

ompl

icat

ions

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Conclusion: Management of massive bleeding

A growing body of evidence supports that high ratios improve outcome

Only in massive bleeding minority of patients

Only a small aspect of massive bleeding management immediate delivery of blood products through pre-established protocols

FFP/PLT/RBC ratios matter to define the content of packs immediately available within the golden hour.

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