Intraoperative haemorrhage and haemostasis Dr. med. Christian Quadri Capoclinica Anestesia, ORL
Intraoperative haemorrhage and haemostasis Dr. med. Christian Quadri Capoclinica Anestesia, ORL
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“Haemostasis is like love. Everybody talks about it, nobody understands it.” JH Levy 2000
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Disclosure
- No conflict of interests
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Contents
1. Introduction 2. Pro-coagulants use in case of haemorrhage
3. Take home messages
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Introduction
- Does the problem exist ?
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Introduction
Bleeding: ü Leading cause of preventable death in trauma ü Leading cause of maternal mortality in resource-poor
countries and severe morbidity in resource-rich countries
ü Blood transfusions associated with several adverse patient outcomes
Cothren CC et al. World J Surg 2007; 31:1507-1511
Collis RE, Collins PW. Anaesthesia 2015; 70 (Suppl. 1): 78–86
Withlock LW et al. BMJ 2015; 2015;350:h3037
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Introduction
Detection and treatm
ent of preoperative anaem
ia
Optim
ize haemostasis
-> minim
ize blood loss
www.blood.gov.au/pbm-guidelines
Harnessing + optim
izing patient physiological reserve of anaem
ia (incl. transf. trigger)
Anesth Analg 2017 Oct 19; Epub ahead of print
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Introduction
Detection and treatment of preoperative anaemia
Optim
ize haemostasis
-> minim
ize blood loss
www.blood.gov.au/pbm-guidelines
Harnessing + optim
izing patient physiological reserve of anaem
ia (incl. transf. trigger)
Anesth Analg 2017 Oct 19; Epub ahead of print
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Introduction
Detection and treatm
ent of preoperative anaem
ia
Harnessing + optim
izing patient physiological reserve of anaem
ia (incl. transf. trigger)
Optimize haemostasis -> minimize blood loss www.blood.gov.au/pbm-guidelines
Anesth Analg 2017 Oct 19; Epub ahead of print
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Introduction
www.blood.gov.au/pbm-guidelines
Detection and treatm
ent of preoperative anaem
ia
Optim
ize haemostasis
-> minim
ize blood loss
Harnessing + optimizing patient physiological reserve of anaemia (incl. transfusion trigger)
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Introduction
Mezar T et al. JAMA Surg 2017; 152 (6):574-580
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Introduction
• Beds for acute treatment: 282 • 2017: 1996 U of RBCs, 460 U FFP, 140 Tc concentrates
• MT’s ?
Distribuzione letti nel canton Ticino (01.01.2018), DSS Trasfusione CRS Svizzera Italiana
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Introduction
Haemorrhage
Haemorrhage
Injury, Int. J. Care Injured 2017; 48: 5-12
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Introduction
- Haemostatic resuscitation based on tests and coagulation factor concentrates driven?
Innerhofer P. Lancet Haematol. 2017; 4: 258-271
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- Empiric administration of blood products in predefined and fixed ratio?
: :FFP Platelets PRBC
Introduction
Holcomb JB. Jama Surg. 2013; 148: 127-36.
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Introduction
ROTEM®
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Introduction
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Viscoelastic Testing
From Winearels J et al. Injury; 2017; 48:230-242
Rotem.de
ROTEM®
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Viscoelastic Testing
From Schöchl H et al. Critical Care. 2010; 14(2):R55
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Levy JH Anesthesiology. 2018; 128: 657-70
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Tranexamic Acid
- Over 20,000 bleeding trauma: v tranexamic acid or matching placebo
- Tranexamic acid 1g + 1g over 8 hours
Lancet; 2010; 376:23-32
Ø Mortality was reduced with tranexamic acid (14.5 vs. 16.0%; P = 0.0035)
Ø Only ≈5% of patients died because of bleeding
Ø Only 50% of patients received blood transfusions Ø No difference in the amount of blood transfused between
groups à Mechanism of action ?
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Fibrinolysis
J Thromb Haemost 2013; 11: 307–314
- Prospective cohort study of 303 trauma patients
- Fibrinolytic activation: plasmin–antiplasmin (PAP) complex, Thromboelastometry (TEM)
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Fibrinolysis
Ø Fibrinolytic activation is associated with the degree of shock and the injury severity
J Thromb Haemost 2013; 11: 307–314
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Fibrinolysis
% m
orta
lity
J Thromb Haemost 2013; 11: 307–314
% o
f pat
ient
s
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Fibrinolysis
J Trauma Acute Care Surg. 2014; 77(6): 811–817
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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 2016. 20:100
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Tranexamic Acid
J Surg Res 2013; 184: 880-887
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
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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
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Fibrinogen
From John W. Weisel, PhD, University of Pennsylvania
Anesth Analg 2012; 114: 261–273
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Anesth Analg 1995; 81: 360-365
Fibrinogen
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2.4 g/l Low Fibrinogen by patients with acute trauma coagulopathy
1.6 g/l
Ø Fibrinogen depletion associated with poor outcome Ø Fibrinogen level do not normalize with high dose of FFP Ø Correction of the coagulopathy ex vivo with fibrinogen concentrate
J Thromb Haemost 2012; 10: 1342–1351
Fibrinogen
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Fibrinogen
J Thromb Haemost 2007; 5: 266–73
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Fibrinogen
British Journal of Anaesthesia; 2015: 114 (4): 623–33
Ø 2g Fibrinogen vs placebo in patient with severe PPH
Ø Primary outcome: RBC transfusion up to 6 weeks postpartum
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Fibrinogen
British Journal of Anaesthesia; 2015: 114 (4): 623–33
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Fibrinogen
British Journal of Anaesthesia; 2015: 114 (4): 623–33
Conclusion:
Ø No benefit of pre-emptive fibrinogen for severe PPH, if plasma level is normal
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Fibrinogen
British Journal of Anaesthesia; 2015: 114 (4): 623–33
Most relevant population may not have been
included
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Fibrinogen
- 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
Kozek-Langenecker SA et al. Eur J Anaesthesiol. 2017; 34(6): 332-395
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Factor XIII
• Responsible for fibrin crosslinking
• Antifibrinolytic properties by
crosslinking α2-plasmin inhibitor to fibrin
From Levy et al . Transfusion. 2013;53:1120-1131
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Factor XIII
- 272 patients - In patients with lowest clot firmness
v FXIII most important independent modulator
Transfus Med Hemother. 2017; 44:85–92
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Factor XIII
Transfus Med Hemother. 2017; 44:85–92
FXIII activity
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Factor XIII
Stroke 2002; 33(66): 1618-23
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Factor XIII
Haemophilia 2014; 20: 144–148
04.04.2018
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Platelets
- 101 critically-injured trauma patients - Platelets hypofunction:
v 45 % of the patients at admission v 91 % during the stay in the ICU
J Trauma Acute Care Surg. 2012; 73 (1): 13-19
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Platelets
- Maintain platelet count > 50 × 109/l. (Grade 1C) - Maintain platelet count > 100 × 109/l in patients
with ongoing bleeding and/or TBI. (Grade 2C)
Rossaint R et al. et al. Critical Care 2016. 20:100
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Plasmatic haemostasis
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Thrombin generation
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Prothrombin complex concentrate
Anesth Analg 2016; 122(5): 1287–300
PCC
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Prothrombin complex concentrate
- Correct hypofibrinogenemia and thrombocytopenia first
- High thromboembolic postoperative risk
Anesth Analg 2016; 122(5): 1287–300
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Prothrombin complex concentrate
J Trauma Acute Care Surg. 2015; 78 (6): 1220-9
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Fresh Frozen Plasma
- Only 30 ml/Kg FFP adequately corrected all
individual coagulation factors
Br J Haematol 2004;125 (1): 69-73
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Fresh Frozen Plasma
J Am Coll Surg 2010; 210 (6): 957-65
Ø Associated with substantial increase in complications, in particular ARDS
Ø No improvement in survival
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Fresh Frozen Plasma
Anesth Analg 2011; 112 (6): 1289-95
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Take home message
Be prepared !
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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):
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Fibrinogen: take home message
- Key for haemostatic function. First haemostatic factor to reach critical level, especially in trauma
- Treat hypofibrinogenaemia (Fibrinogen concentrate), target 1.5-2 g/l
- PPH: Fibrinogen < 2 g/l à marker for severe haemorrhage
- Pre-emptive administration only in selected cases?
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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
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Platelets: take home message
- In critically-injured platelets dysfunction may be present despite normal counts
- Target: 50 x 109/l. 100 x 109/l in patients with on-going bleeding and/or TBI
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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: 500-1500 I.U.
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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
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