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29/11/2013 How do I treat massive bleeding? Red blood cell / plasma / platelet ratio and massive transfusion protocols Anne GODIER Service dAnesthsie-Ranimation Hopital Cochin Paris G roupe d I ntrt en H mostase P


  1. 29/11/2013 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 G roupe d’ I ntérêt en H émostase P ériopératoire 1

  2. 29/11/2013 Conflicts of interest  Bayer  LFB  BMS-Pfizer  Octapharma  Boehringer-Ingelheim  CSL-Behring  Léo  Sanofi Acknowledgement  Pr Sophie Susen (Lille) 2

  3. 29/11/2013 1:1:1 ratio 3

  4. 29/11/2013 Massive bleeding Severe trauma Post-partum haemorrhage Major surgery (cardiac & aortic surgery) Gastrointestinal bleeding Liver transplantation Massive transfusion Mortality Coagulopathy 4

  5. 29/11/2013 Trauma-induced coagulopathy trauma patient Massive bleeding Fluid loading Shock Massive RBC transfusion Acidosis Hypothermia Dilution Trauma induced Trauma-induced Coagulopathy coagulopathy coagulopathy Adapted from Brohi K, Ann Surg 2007* 5

  6. 29/11/2013 Trauma-induced coagulopathy trauma patient Massive Tissue Injury bleeding Fluid loading Shock Massive RBC transfusion Acidosis Hypothermia Dilution Acute traumatic coagulopathy Trauma induced Trauma-induced Coagulopathy coagulopathy coagulopathy Adapted from Brohi K, Ann Surg 2007* 6

  7. 29/11/2013 Trauma-induced coagulopathy trauma patient Massive Tissue Injury bleeding Inflammation Fluid loading Shock Fibrinolysis Massive RBC transfusion systemic platelet anticoagulation dysfonction activated protein C Acidosis Hypothermia Dilution Acute traumatic coagulopathy Trauma induced Trauma-induced Coagulopathy coagulopathy coagulopathy Adapted from Brohi K, Ann Surg 2007* 7

  8. 29/11/2013 Trauma-induced coagulopathy trauma patient Massive Tissue Injury bleeding Inflammation Fluid loading Shock Fibrinolysis Massive RBC transfusion systemic platelet anticoagulation dysfonction activated protein C Acidosis Hypothermia Dilution Acute traumatic coagulopathy Trauma induced Trauma-induced Coagulopathy coagulopathy coagulopathy Adapted from Brohi K, Ann Surg 2007* 8

  9. 29/11/2013 Early onset of coagulopathy in trauma o On-scene: TAC = trauma-associated coagulopathy injury On-scene Normal Non-overt TAC TAC 20 (44%) 22 (49%) 3 (7%) Admission Normal Non-overt TAC TAC Normal Non-overt TAC TAC Normal Non-overt TAC TAC 16 (36%) 3 (7%) 1 (2%) 16 (36%) 15 (33%) 5 (11%) 0 (0%) 0 (0%) 3 (7%) On-scene and trauma resuscitation room coagulation status Floccard B , et al. Injury 2012;43:26–32 9

  10. 29/11/2013 Reduced Coagulation Factor Activity FII FV FVII FIX FX FXI Facteur Severe trauma patients Jansen JO, J Trauma 2011 10

  11. 29/11/2013 10-15 mL/kg 30 mL/kg Fibrinogène g/L +0.4 +1.0 II % +16 +41 V % +10 +28 VII % +11 +38 IX % +8 +28 X % +15 +37 XI % +9 +23 XII % +30 +44 Br J Haematol 2004;125:69-73 11

  12. 29/11/2013 10-15 mL/kg 30 mL/kg Fibrinogène g/L +0.4 +1.0 II % +16 +41 V % +10 +28 VII % +11 +38 IX % +8 +28 X % +15 +37 XI % +9 +23 XII % +30 +44 Br J Haematol 2004;125:69-73 12

  13. 29/11/2013 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. 13

  14. 29/11/2013 Increasing plasma:RBC ratio  Transfusion with high ratio  Ratio = plasma number / RBC number 14

  15. 29/11/2013 1:1.4 246 trauma patients with massive transfusion FFP:RBC 1:2.5 mortality 1:8 (>10 RBC) 15

  16. 29/11/2013 1:1.4 246 trauma patients with massive transfusion FFP:RBC 1:2.5 mortality 1:8 (>10 RBC) 16

  17. 29/11/2013 Military trauma studies: beneficial effect of high FFP:RBC ratio 17

  18. 29/11/2013 military civilian trauma studies 18

  19. 29/11/2013 Mortality in patients undergoing massive transfusion n=3400 19

  20. 29/11/2013 Mortality in patients undergoing massive transfusion n=3400 20

  21. 29/11/2013 Limitations  retrospective studies (or cohort studies)  missing data  analytical bias  survival bias 21

  22. 29/11/2013 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. 29/11/2013 Platelet : RBC ratio? 23

  24. 29/11/2013 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 24

  25. 29/11/2013 25

  26. 29/11/2013 Retrospective data regarding platelet transfusion mortality variation between trauma receiving large amount of platelets copared to small amount % 26

  27. 29/11/2013 Retrospective data regarding platelet transfusion % mortality mortality variation between trauma receiving large amount of platelets copared to small amount % low high ratios ratios 27

  28. 29/11/2013 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 50 × 10 9 /l. (Grade 1C) We suggest maintenance of a platelet count above 100 × 10 9 /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. 29/11/2013 Increasing ratios is not enough 1:1:1 Ratio : a time-dependent variable t 29

  30. 29/11/2013 Ratio = FFP / RBC Deficit = RBC - FFP * ≤ 2 >6 O Mortality of trauma patients grouped by deficit status 30

  31. 29/11/2013 Reducing transfusion delay carefully constructed massive transfusion protocol  local agreement with the blood bank  products available as soon as possible  healthcare professionals 31

  32. 29/11/2013 Protocol : 10 RBC 4 FFP 2 platelets  ratio 1:2.5 * * 32

  33. 29/11/2013 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. 29/11/2013 Packs Godier A, Samama M, Susen S. Curr Opin Anesthesiol 2012 34

  35. 29/11/2013 Packs Godier A, Samama M, Susen S. Curr Opin Anesthesiol 2012 35

  36. 29/11/2013 Immediate availability of plasma in the 1 st pack Thawing plasma thawed AB group plasma radio wave-based Freeze-dried plasma stored for immediate availability thawing technology together with O group RBC 36

  37. 29/11/2013 1:1:1 ratio in blood transfusion: many argues in massive transfusion non massively transfused patients? 37

  38. 29/11/2013 Mortality in patients undergoing surgery without massive transfusion 38

  39. 29/11/2013 overall complications  increase in complications  no improvement in survival   in complications as  volumes of plasma number of units of plasma transfused in 12 hours 39

  40. 29/11/2013 overall complications  increase in complications  no improvement in survival   in complications as  volumes of plasma number of units of plasma transfused in 12 hours 40

  41. 29/11/2013 overall complications  increase in complications  no improvement in survival   in complications as  volumes of plasma number of units of plasma transfused in 12 hours 41

  42. 29/11/2013 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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