Intraoperative haemorrhage and haemostasis. Dr. med. Christian Quadri Capoclinica Anestesia, ORL
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1 Intraoperative haemorrhage and haemostasis Dr. med. Christian Quadri Capoclinica Anestesia, ORL
2 Haemostasis is like love. Everybody talks about it, nobody understands it. JH Levy 2000 Intraoperative Haemorrhage and Haemostasis Pag. 2
3 Disclosure - No conflict of interests Intraoperative Haemorrhage and Haemostasis Pag. 3
4 Intraoperative Haemorrhage and Haemostasis Pag. 4
5 Contents 1. Introduction 2. Pro-coagulants use in case of haemorrhage 3. Take home messages Intraoperative Haemorrhage and Haemostasis Pag. 5
6 Introduction - Does the problem exist? Intraoperative Haemorrhage and Haemostasis Pag. 6
7 Introduction Bleeding: ü Leading cause of preventable death in trauma Cothren CC et al. World J Surg 2007; 31: ü Leading cause of maternal mortality in resource-poor countries and severe morbidity in resource-rich countries Collis RE, Collins PW. Anaesthesia 2015; 70 (Suppl. 1): ü Blood transfusions associated with several adverse patient outcomes Withlock LW et al. BMJ 2015; 2015;350:h3037 Intraoperative Haemorrhage and Haemostasis Pag. 7
8 Introduction Anesth Analg 2017 Oct 19; Epub ahead of print Detection and treatment of preoperative anaemia Optimize haemostasis -> minimize blood loss Harnessing + optimizing patient physiological reserve of anaemia (incl. transf. trigger) Intraoperative Haemorrhage and Haemostasis Pag. 8
9 Introduction Anesth Analg 2017 Oct 19; Epub ahead of print Detection and treatment of preoperative anaemia Optimize haemostasis -> minimize blood loss Harnessing + optimizing patient physiological reserve of anaemia (incl. transf. trigger) Intraoperative Haemorrhage and Haemostasis Pag. 9
10 Introduction Anesth Analg 2017 Oct 19; Epub ahead of print Detection and treatment of preoperative anaemia Harnessing + optimizing patient physiological reserve of anaemia (incl. transf. trigger) Optimize haemostasis -> minimize blood loss Intraoperative Haemorrhage and Haemostasis Pag. 10
11 Introduction Detection and treatment of preoperative anaemia Optimize haemostasis -> minimize blood loss Harnessing + optimizing patient physiological reserve of anaemia (incl. transfusion trigger) Intraoperative Haemorrhage and Haemostasis Pag. 11
12 Introduction Mezar T et al. JAMA Surg 2017; 152 (6): Intraoperative Haemorrhage and Haemostasis Pag. 12
13 Introduction Beds for acute treatment: : 1996 U of RBCs, 460 U FFP, 140 Tc concentrates MT s? Distribuzione letti nel canton Ticino ( ), DSS Trasfusione CRS Svizzera Italiana Intraoperative Haemorrhage and Haemostasis Pag. 13
14 Introduction Injury, Int. J. Care Injured 2017; 48: 5-12 Haemorrhage Haemorrhage Intraoperative Haemorrhage and Haemostasis Pag. 14
15 Intraoperative Haemorrhage and Haemostasis Pag. 15
16 Introduction - Haemostatic resuscitation based on tests and coagulation factor concentrates driven? Innerhofer P. Lancet Haematol. 2017; 4: Intraoperative Haemorrhage and Haemostasis Pag. 16
17 Introduction - Empiric administration of blood products in predefined and fixed ratio? : : PRBC FFP Platelets Holcomb JB. Jama Surg. 2013; 148: Intraoperative Haemorrhage and Haemostasis Pag. 17
18 Introduction ROTEM Intraoperative Haemorrhage and Haemostasis Pag. 18
19 Introduction Intraoperative Haemorrhage and Haemostasis Pag. 19
20 Viscoelastic Testing ROTEM Rotem.de From Winearels J et al. Injury; 2017; 48: Intraoperative Haemorrhage and Haemostasis Pag. 20
21 Viscoelastic Testing From Schöchl H et al. Critical Care. 2010; 14(2):R55 Intraoperative Haemorrhage and Haemostasis Pag. 21
22 Intraoperative Haemorrhage and Haemostasis Pag. 22 Levy JH Anesthesiology. 2018; 128:
23 Tranexamic Acid Lancet; 2010; 376:23-32 Ø Mortality was reduced with tranexamic acid (14.5 vs. 16.0%; P = ) - Over 20,000 bleeding trauma: v tranexamic acid or matching placebo Ø Only 5% of patients died because of bleeding Ø Only 50% of patients received blood transfusions - Tranexamic acid 1g + 1g over 8 hours Ø No difference in the amount of blood transfused between groups à Mechanism of action? Intraoperative Haemorrhage and Haemostasis Pag. 23
24 Fibrinolysis J Thromb Haemost 2013; 11: Prospective cohort study of 303 trauma patients - Fibrinolytic activation: plasmin antiplasmin (PAP) complex, Thromboelastometry (TEM) Intraoperative Haemorrhage and Haemostasis Pag. 24
25 Fibrinolysis J Thromb Haemost 2013; 11: Ø Fibrinolytic activation is associated with the degree of shock and the injury severity Intraoperative Haemorrhage and Haemostasis Pag. 25
26 Fibrinolysis J Thromb Haemost 2013; 11: % of patients % mortality Intraoperative Haemorrhage and Haemostasis Pag. 26
27 Fibrinolysis J Trauma Acute Care Surg. 2014; 77(6): Intraoperative Haemorrhage and Haemostasis Pag. 27
28 Tranexamic Acid - Tranexamic acid: 1g as soon as possible to the trauma patient who is bleeding or at risk of significant hemorrhage (+1 g over 8 h). (Grade 1A) - Tranexamic acid: within 3 h after injury. (Grade 1B) Rossaint R et al. et al. Critical Care :100 Intraoperative Haemorrhage and Haemostasis Pag. 28
29 Tranexamic Acid J Surg Res 2013; 184: Ø 1114 patients enrolled in RTs Ø TXA significantly reduce perioperative blood loss and blood transfusion following unilateral TKA Ø No increased risk of venous thromboembolisms or other adverse events Intraoperative Haemorrhage and Haemostasis Pag. 29
30 Tranexamic Acid Ø Death due to bleeding and laparotomy to control bleeding significantly reduced Ø Within 3 hours of giving birth Ø No increased risk of thromboembolic events Intraoperative Haemorrhage and Haemostasis Pag. 30
31 Fibrinogen Anesth Analg 2012; 114: From John W. Weisel, PhD, University of Pennsylvania Intraoperative Haemorrhage and Haemostasis Pag. 31
32 Fibrinogen Anesth Analg 1995; 81: Intraoperative Haemorrhage and Haemostasis Pag. 32
33 Fibrinogen J Thromb Haemost 2012; 10: Ø Fibrinogen depletion associated with poor outcome 2.4 g/l Ø Fibrinogen level do not normalize with high dose of FFP Low Fibrinogen by patients with acute trauma coagulopathy 1.6 g/l Ø Correction of the coagulopathy ex vivo with fibrinogen concentrate Intraoperative Haemorrhage and Haemostasis Pag. 33
34 Fibrinogen J Thromb Haemost 2007; 5: Intraoperative Haemorrhage and Haemostasis Pag. 34
35 Fibrinogen British Journal of Anaesthesia; 2015: 114 (4): Ø 2g Fibrinogen vs placebo in patient with severe PPH Ø Primary outcome: RBC transfusion up to 6 weeks postpartum Intraoperative Haemorrhage and Haemostasis Pag. 35
36 Fibrinogen Intraoperative Haemorrhage and Haemostasis Pag. 36 British Journal of Anaesthesia; 2015: 114 (4):
37 Fibrinogen Conclusion: Ø No benefit of pre-emptive fibrinogen for severe PPH, if plasma level is normal Intraoperative Haemorrhage and Haemostasis Pag. 37 British Journal of Anaesthesia; 2015: 114 (4):
38 Fibrinogen Most relevant population may not have been included Intraoperative Haemorrhage and Haemostasis Pag. 38 British Journal of Anaesthesia; 2015: 114 (4):
39 Fibrinogen Kozek-Langenecker SA et al. Eur J Anaesthesiol. 2017; 34(6): Fibrinogen concentration of less than 1.5 to 2g/l is considered as hypofibrinogenaemia in acquired coagulopathy and is associated with increased bleeding risk. C - We recommend treatment of hypofibrinogenaemia in bleeding patients. 1C Intraoperative Haemorrhage and Haemostasis Pag. 39
40 Factor XIII Responsible for fibrin crosslinking Antifibrinolytic properties by crosslinking α2-plasmin inhibitor to fibrin From Levy et al. Transfusion. 2013;53: Intraoperative Haemorrhage and Haemostasis Pag. 40
41 Factor XIII Transfus Med Hemother. 2017; 44: patients - In patients with lowest clot firmness v FXIII most important independent modulator Intraoperative Haemorrhage and Haemostasis Pag. 41
42 Factor XIII Transfus Med Hemother. 2017; 44:85 92 FXIII activity Intraoperative Haemorrhage and Haemostasis Pag. 42
43 Factor XIII Stroke 2002; 33(66): Intraoperative Haemorrhage and Haemostasis Pag. 43
44 Factor XIII Haemophilia 2014; 20: Intraoperative Haemorrhage and Haemostasis Pag. 44
45 Platelets J Trauma Acute Care Surg. 2012; 73 (1): critically-injured trauma patients - Platelets hypofunction: v 45 % of the patients at admission v 91 % during the stay in the ICU Intraoperative Haemorrhage and Haemostasis Pag. 45
46 Platelets - Maintain platelet count > /l. (Grade 1C) - Maintain platelet count > /l in patients with ongoing bleeding and/or TBI. (Grade 2C) Rossaint R et al. et al. Critical Care :100 Intraoperative Haemorrhage and Haemostasis Pag. 46
47 Plasmatic haemostasis Intraoperative Haemorrhage and Haemostasis Pag. 47
48 Thrombin generation Intraoperative Haemorrhage and Haemostasis Pag. 48
49 Prothrombin complex concentrate Anesth Analg 2016; 122(5): PCC Intraoperative Haemorrhage and Haemostasis Pag. 49
50 Prothrombin complex concentrate Anesth Analg 2016; 122(5): Correct hypofibrinogenemia and thrombocytopenia first - High thromboembolic postoperative risk Intraoperative Haemorrhage and Haemostasis Pag. 50
51 Prothrombin complex concentrate J Trauma Acute Care Surg. 2015; 78 (6): Intraoperative Haemorrhage and Haemostasis Pag. 51
52 Fresh Frozen Plasma Br J Haematol 2004;125 (1): Only 30 ml/kg FFP adequately corrected all individual coagulation factors Intraoperative Haemorrhage and Haemostasis Pag. 52
53 Fresh Frozen Plasma J Am Coll Surg 2010; 210 (6): Ø Associated with substantial increase in complications, in particular ARDS Ø No improvement in survival Intraoperative Haemorrhage and Haemostasis Pag. 53
54 Fresh Frozen Plasma Anesth Analg 2011; 112 (6): Intraoperative Haemorrhage and Haemostasis Pag. 54
55 Take home message Be prepared! Intraoperative Haemorrhage and Haemostasis Pag. 55
56 TXA: take home message - Trauma: < 3 h v fibrinolysis activation à increased mortality v waiting for results about fibrinolysis shutdown - Orthopedic surgery: - Obstetric: in case of PPH < 3 h - Cardiac surgery (CPB): Intraoperative Haemorrhage and Haemostasis Pag. 56
57 Fibrinogen: take home message - Key for haemostatic function. First haemostatic factor to reach critical level, especially in trauma - Treat hypofibrinogenaemia (Fibrinogen concentrate), target g/l - PPH: Fibrinogen < 2 g/l à marker for severe haemorrhage - Pre-emptive administration only in selected cases? Intraoperative Haemorrhage and Haemostasis Pag. 57
58 Factor XIII: take home message - Consider measurement in severe bleeding - Consider administration in activity < 60% - Critical level are probably rapidly reached in severe PPH - Strong evidence is still lacking Intraoperative Haemorrhage and Haemostasis Pag. 58
59 Platelets: take home message - In critically-injured platelets dysfunction may be present despite normal counts - Target: 50 x 10 9 /l. 100 x 10 9 /l in patients with ongoing bleeding and/or TBI Intraoperative Haemorrhage and Haemostasis Pag. 59
60 Prothrombin complex concentrate: Take home message - Off label use in non Vitamin K antagonist related bleeding - Successfully used in Trauma Induced Coagulopathy - Administration should be based on (viscoelastic) measurements, after correction of hypofibrinogenaemia and thrombocytopenia - Thromboembolic risks. Low dosage: I.U. Intraoperative Haemorrhage and Haemostasis Pag. 60
61 Fresh Frozen Plasma: take home message - Limited effect to correct coagulation disturbances - More complications if administered to patients not requiring massive transfusion - Potential protective effect on endothelial Glycocalyx Intraoperative Haemorrhage and Haemostasis Pag. 61
62 Intraoperative Haemorrhage and Haemostasis Pag. 62
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