Groupe d Intérêt en Hémostase Périopératoire
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1 How do I treat massive bleeding? Red blood cell / plasma / platelet ratio and massive transfusion protocols Anne GODIER Service d Anesthésie-Réanimation Hopital Cochin Paris Groupe d Intérêt en Hémostase Périopératoire 1
2 Conflicts of interest LFB Octapharma CSL-Behring Bayer BMS-Pfizer Boehringer-Ingelheim Léo Sanofi Pr Sophie Susen (Lille) Acknowledgement 2
3 1:1:1 ratio 3
4 Massive bleeding Severe trauma Post-partum haemorrhage Major surgery (cardiac & aortic surgery) Gastrointestinal bleeding Liver transplantation Massive transfusion Coagulopathy Mortality 4
5 Trauma-induced coagulopathy trauma patient Massive bleeding Shock Fluid loading Massive RBC transfusion Acidosis Hypothermia Dilution Trauma-induced coagulopathy Coagulopathy Adapted from Brohi K, Ann Surg 2007* 5
6 Trauma-induced coagulopathy trauma patient Tissue Injury Massive bleeding Shock Fluid loading Massive RBC transfusion Acute traumatic coagulopathy Acidosis Hypothermia Dilution Trauma-induced coagulopathy Coagulopathy Adapted from Brohi K, Ann Surg 2007* 6
7 Trauma-induced coagulopathy trauma patient Fibrinolysis Tissue Injury systemic anticoagulation activated protein C Inflammation platelet dysfonction Acute traumatic coagulopathy Shock Acidosis Massive bleeding Hypothermia Fluid loading Massive RBC transfusion Dilution Trauma-induced coagulopathy Coagulopathy Adapted from Brohi K, Ann Surg 2007* 7
8 Trauma-induced coagulopathy trauma patient Fibrinolysis Tissue Injury systemic anticoagulation activated protein C Inflammation platelet dysfonction Acute traumatic coagulopathy Shock Acidosis Massive bleeding Hypothermia Fluid loading Massive RBC transfusion Dilution Trauma-induced coagulopathy Coagulopathy Adapted from Brohi K, Ann Surg 2007* 8
9 Early onset of coagulopathy in trauma o On-scene: TAC = trauma-associated coagulopathy On-scene injury Admission Normal 20 (44%) Non-overt TAC 22 (49%) TAC 3 (7%) Normal 16 (36%) Non-overt TAC 3 (7%) TAC 1 (2%) Normal 16 (36%) Non-overt TAC 15 (33%) TAC 5 (11%) Normal 0 (0%) Non-overt TAC 0 (0%) TAC 3 (7%) On-scene and trauma resuscitation room coagulation status Floccard B, et al. Injury 2012;43:
10 Reduced Coagulation Factor Activity FII FV FVII FIX FX FXI Facteur Severe trauma patients Jansen JO, J Trauma
11 Br J Haematol 2004;125: ml/kg 30 ml/kg Fibrinogène g/l II % V % VII % IX % X % XI % XII %
12 Br J Haematol 2004;125: ml/kg 30 ml/kg Fibrinogène g/l II % V % VII % IX % X % XI % XII %
13 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:S
14 Increasing plasma:rbc ratio Transfusion with high ratio Ratio = plasma number / RBC number 14
15 246 trauma patients with massive transfusion (>10 RBC) 1:1.4 FFP:RBC 1:2.5 mortality 1:8 15
16 246 trauma patients with massive transfusion (>10 RBC) 1:1.4 FFP:RBC 1:2.5 mortality 1:8 16
17 Military trauma studies: beneficial effect of high FFP:RBC ratio 17
18 military civilian trauma studies 18
19 Mortality in patients undergoing massive transfusion n=
20 Mortality in patients undergoing massive transfusion n=
21 Limitations retrospective studies (or cohort studies) missing data analytical bias survival bias 21
22 april 2013 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. 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 blood cell ratio of at least 1:2. (Grade 2C) 22
23 Platelet : RBC ratio? 23
24 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=
25 25
26 Retrospective data regarding platelet transfusion % mortality variation between trauma receiving large amount of platelets copared to small amount 26
27 Retrospective data regarding platelet transfusion % mortality % mortality variation between trauma receiving large amount of platelets copared to small amount low ratios high ratios 27
28 april 2013 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. We recommend that platelets be administered to maintain a platelet count above /l. (Grade 1C) We suggest maintenance of a platelet count above /l in patients with ongoing bleeding and/or TBI. (Grade 2C) 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 28
29 Increasing ratios is not enough 1:1:1 Ratio : a time-dependent variable t 29
30 Ratio = FFP / RBC Deficit = RBC - FFP * 2 >6 O Mortality of trauma patients grouped by deficit status 30
31 Reducing transfusion delay carefully constructed massive transfusion protocol local agreement with the blood bank products available as soon as possible healthcare professionals 31
32 Protocol : 10 RBC 4 FFP 2 platelets ratio 1:2.5 * * 32
33 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 33
34 Packs Godier A, Samama M, Susen S. Curr Opin Anesthesiol
35 Packs Godier A, Samama M, Susen S. Curr Opin Anesthesiol
36 Immediate availability of plasma in the 1 st pack Thawing plasma thawed AB group plasma stored for immediate availability together with O group RBC radio wave-based thawing technology Freeze-dried plasma 36
37 1:1:1 ratio in blood transfusion: many argues in massive transfusion non massively transfused patients? 37
38 Mortality in patients undergoing surgery without massive transfusion 38
39 increase in complications no improvement in survival in complications as volumes of plasma overall complications number of units of plasma transfused in 12 hours 39
40 increase in complications no improvement in survival in complications as volumes of plasma overall complications number of units of plasma transfused in 12 hours 40
41 increase in complications no improvement in survival in complications as volumes of plasma overall complications number of units of plasma transfused in 12 hours 41
42 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. 42
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