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29/11/2013
1
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
Trauma-induced coagulopathy
Massive RBC transfusion
Adapted from Brohi K, Ann Surg 2007*
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Trauma-induced coagulopathy
DilutionHypothermiaAcidosis
Fluid loadingShock
Massivebleeding
Coagulopathy
Acute traumatic coagulopathy
Tissue Injury
trauma patient
Trauma induced coagulopathy
Trauma-induced coagulopathy
Massive RBC transfusion
Adapted from Brohi K, Ann Surg 2007*
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Trauma-induced coagulopathy
DilutionHypothermiaAcidosis
Fluid loadingShock
Massivebleeding
Coagulopathy
Acute traumatic coagulopathy
Tissue Injury
InflammationFibrinolysis
systemicanticoagulation
activated protein C
trauma patient
Trauma induced coagulopathy
Trauma-induced coagulopathy
Massive RBC transfusionplatelet
dysfonction
Adapted from Brohi K, Ann Surg 2007*
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Trauma-induced coagulopathy
DilutionHypothermiaAcidosis
Fluid loadingShock
Massivebleeding
Coagulopathy
Acute traumatic coagulopathy
Tissue Injury
InflammationFibrinolysis
systemicanticoagulation
activated protein C
trauma patient
Trauma induced coagulopathy
Trauma-induced coagulopathy
Massive RBC transfusionplatelet
dysfonction
Adapted from Brohi K, Ann Surg 2007*
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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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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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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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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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