Intraoperative haemorrhage and haemostasis

Intraoperative haemorrhage and haemostasis Dr. med. Christian Quadri Capoclinica Anestesia, ORL

Intraoperative Haemorrhage and Haemostasis - 12.04.2018 - Pag. 2

“Haemostasis is like love. Everybody talks about it, nobody understands it.” JH Levy 2000


Disclosure

-  No conflict of interests



Contents

1.  Introduction 2.  Pro-coagulants use in case of haemorrhage

3.  Take home messages


Introduction

-  Does the problem exist ?


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


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


Introduction

Detection and treatment of preoperative anaemia

Optim

ize haemostasis

-> minim

ize blood loss


Harnessing + optim





Introduction



ia

Harnessing + optim



Optimize haemostasis -> minimize blood loss www.blood.gov.au/pbm-guidelines



Introduction




ia

Optim

ize haemostasis

-> minim

ize blood loss

Harnessing + optimizing patient physiological reserve of anaemia (incl. transfusion trigger)


Introduction

Mezar T et al. JAMA Surg 2017; 152 (6):574-580


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


Introduction

Haemorrhage

Haemorrhage

Injury, Int. J. Care Injured 2017; 48: 5-12



Introduction

-  Haemostatic resuscitation based on tests and coagulation factor concentrates driven?

Innerhofer P. Lancet Haematol. 2017; 4: 258-271


-  Empiric administration of blood products in predefined and fixed ratio?

: :FFP Platelets PRBC

Introduction

Holcomb JB. Jama Surg. 2013; 148: 127-36.


Introduction

ROTEM®


Introduction


Viscoelastic Testing

From Winearels J et al. Injury; 2017; 48:230-242

Rotem.de

ROTEM®


Viscoelastic Testing

From Schöchl H et al. Critical Care. 2010; 14(2):R55


Levy JH Anesthesiology. 2018; 128: 657-70


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 ?


Fibrinolysis

J Thromb Haemost 2013; 11: 307–314

-  Prospective cohort study of 303 trauma patients

-  Fibrinolytic activation: plasmin–antiplasmin (PAP) complex, Thromboelastometry (TEM)


Fibrinolysis

Ø  Fibrinolytic activation is associated with the degree of shock and the injury severity



Fibrinolysis

% m

orta

lity


% o

f pat

ient

s


Fibrinolysis

J Trauma Acute Care Surg. 2014; 77(6): 811–817


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


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


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


Fibrinogen

From John W. Weisel, PhD, University of Pennsylvania

Anesth Analg 2012; 114: 261–273


Anesth Analg 1995; 81: 360-365

Fibrinogen


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


Fibrinogen



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


Fibrinogen



Fibrinogen


Conclusion:

Ø  No benefit of pre-emptive fibrinogen for severe PPH, if plasma level is normal


Fibrinogen


Most relevant population may not have been

included


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


Factor XIII

•  Responsible for fibrin crosslinking

•  Antifibrinolytic properties by

crosslinking α2-plasmin inhibitor to fibrin

From Levy et al . Transfusion. 2013;53:1120-1131


Factor XIII

-  272 patients -  In patients with lowest clot firmness

v  FXIII most important independent modulator

Transfus Med Hemother. 2017; 44:85–92


Factor XIII

Transfus Med Hemother. 2017; 44:85–92

FXIII activity


Factor XIII

Stroke 2002; 33(66): 1618-23


Factor XIII

Haemophilia 2014; 20: 144–148

04.04.2018


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


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


Plasmatic haemostasis


Thrombin generation


Prothrombin complex concentrate

Anesth Analg 2016; 122(5): 1287–300

PCC



-  Correct hypofibrinogenemia and thrombocytopenia first

-  High thromboembolic postoperative risk

Anesth Analg 2016; 122(5): 1287–300



J Trauma Acute Care Surg. 2015; 78 (6): 1220-9


Fresh Frozen Plasma

-  Only 30 ml/Kg FFP adequately corrected all

individual coagulation factors

Br J Haematol 2004;125 (1): 69-73


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


Fresh Frozen Plasma

Anesth Analg 2011; 112 (6): 1289-95


Take home message

Be prepared !


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):


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?


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


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


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.


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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Intraoperative haemorrhage and haemostasis

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