OLT Without Blood

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LIVER TRANSPLANTATIONLIVER TRANSPLANTATIONWITHOUT BLOOD LOSSWITHOUT BLOOD LOSS --

Myth or Reality

Odisseeva E., Vladov N*., Petrov N.

Department of Anesthesiology and Intensive Care

*Clinic of Hepatobiliary, Pancreatic and Transplant Surgery

Military Medical Academy ² Sofia



Objectives: The mythObjectives: The myth ² ² Liver transplantationLiver transplantation

is associated with high blood loss and largeis associated with high blood loss and largeamount of blood transfusions is neededamount of blood transfusions is needed

y The patient with liver disease and cirrhosis

usually bleeds more in the operating roomdue to coagulopathy

y We believe we must correct coagulopathy

by transfusion of blood productsy It· unusual ² liver transplantation without

transfusion of blood products



The patient with liver disease and cirrhosisThe patient with liver disease and cirrhosis

usually bleeds more in the operating room ???usually bleeds more in the operating room ???

y Check for preexisting coagulationabnormalities:

x PT/INR

x APTT

x Fibrinogen

x Platelet count

y We believe we must correct them by

transfusion of blood products:x Fresh frozen plasma

x Protrombin complex

x Cryoprecipitate

x Platelet concentrates



TransfusionTransfusion of fresh frozen plasma in critically illof fresh frozen plasma in critically illsurgical patients is associated with an increased risk of surgical patients is associated with an increased risk of infectioninfection..SaraniSarani B et al. Division of B et al. Division of TraumatologyTraumatology and Surgical Critical Care, Department of Surgery,and Surgical Critical Care, Department of Surgery,

University of Pennsylvania, School of Medicine, Philadelphia, PA, USA. [email protected] of Pennsylvania, School of Medicine, Philadelphia, PA, USA. [email protected]

complication relative risk

ventilator-associated pneumonia with shock 5.42 ( 2.73-10.74)

ventilator-associated pneumonia without shock 1.97 (1.03-3.78)bloodstream infection with shock 3.35 (1.69-6.64)

undifferentiated septic shock 3.22 (1.84-5.61).

all infections 2.99 (2.28-3.93)

The association between fresh frozen plasma aplicationand infectious complications remainedsignificant in the multivariate model, with an odds ratio of infection per unit of fresh frozen

plasma transfused equal to 1.039 (1.013-1.067).This odds ratio resembled that noted for each

unit of packed red blood cells, 1.074 (1.043-1.106).

CONCLUSIONS: Transfusion of fresh frozen plasma is associated with an increased risk of

infections in critically ill patients.

PMID: 18379235 [PubMed - indexed for MEDLINE]



Marieke T. de Boer, MD* et al.AnesthAnalg 2008;106:32²44)No. 1, January 2008



15% increase in

6-month mortality 33% increase in

6- month

mortality

Marieke T. de Boer, MD* et al.AnesthAnalg 2008;106:32²44)No. 1, January 2008



Correction with Blood ProductsCorrection with Blood Products

y Efficiency has never been proven

y Correction of prolonged INR requiresseveral units of FFP

y Transfusion of blood components isassociated with important side effects:

x Viral and bacterial transmissions

x Immunosuppresion ² TRIM

x Increased rate of infectious complications

x TRALI

x TACO ² acute fluid overload ( i.e. FFP)

x etc



Key question is:Key question is:

y What is the best strategy to minimizeblood loss in patients undergoing liver

transplantation?Should we correct or to contract ?

Liberal infusion versus fluid restriction?

Is there evidence for best practice?



Is Haemostatic Function Really ThatIs Haemostatic Function Really That

AAbnormal in Cirrhotic Patientsbnormal in Cirrhotic Patientsy Primary hemostasis

x Platelets ² von Willebrand Factor ² endothelium

y Secondary hemostasis

x Plasmatic coagulation / Thrombin

generation



Definition of Definition of HemostasisHemostasis

Bleeding to

Death

Clotting to

Death

Haemostasis : ́ Live in the Balance ́



Procoagulant

activity

Fiblinolytic

activity

Anticoagulant

activity

Antifibrinolityc

activity

NormalHemostasis



The Concept of RebalancedThe Concept of Rebalanced HemostasisHemostasisinin PatientsPatients withwith LiverLiver DiseaseDisease

Haemostatic changes

impairing haemostasis

Haemostatic changes

promoting haemostasis

Low platelet count

Impaired platelet functionand plateletvessel wall interaction

Primary hemostasis levels of vWF

Decreased levels of ADAMTS-13

Factor II, V, VII, IX, X, XIQuantitative and qualitativeabnormalities in fibrinogen

Secondary hemostasis

Elevated levels of FVIII, Protein C, protein S, protein Z,

AT(III), heparin-CoFII,2-

macroglobulin

2-anti-plasmin, TAFI, HRG

t-PA (not balanced by PAI-

1 levels)Fibrinolysis

plasminogen

From T. Lismanet al. J Hepatol 2002;37:280-7

Rebalansing



The Concept of RebalancedThe Concept of Rebalanced HemostasisHemostasisin Patients with Liver Diseasein Patients with Liver Disease ² ²

PrimaryPrimary hemostasishemostasis

Low platelet count,Impaired plateletfunction and

platelet vessel wallinteraction



FVIII and vWF

Low platelet count,

Impaired plateletfunction and

platelet vessel wallinteraction

TheThe ConseptConsept of Rebalancedof Rebalanced HemostasisHemostasisin Patients with Liver Diseasein Patients with Liver Disease ² ²

PrimaryPrimary hemostasishemostasis




SecondarySecondary hemostasishemostasis

Procoagulants

Factor II, V, VII, IX, X, XIQuantitative and qualitative

abnormalities in fibrinogen



Procoagulants Anticoagulants

Factor II, V, VII, IX, X, XIQuantitative and qualitative

abnormalities in fibrinogen

Factor VIII Protein C,

protein S, protein Z,

AT(III),

heparin-CoFII, 2-macroglobulin

Generation of thrombin is normal in cirrhosis


SecondarySecondary hemostasishemostasis



y The overall hemostatic function in

patients with cirrhosis seems less

disturbed than what is traditionally

assumed on coagulation test and

platelet count



ThromboelastogramThromboelastogram(TEG)(TEG)

Global analysis of whole

coagulation process

Sensitive to activators andinhibitors

Visual assessment of clotstrength & stability



Preoperative coagulation Profile andPreoperative coagulation Profile andbleeding during Liver Transplantationbleeding during Liver Transplantation

y Conventional coagulation tests are a poorpredictor of blood loss during LT

Reyle-Hahn I Rossaint. Liver TransplSurg 1997

Steib et al. Can J Anaesth 2001Massicotte et al. Transplantation 2008

y Conventional coagulation tests do not

describe the really state of haemostasis inthe patients with LD.



y Is it possible other factors to be moreimportant determinants of bleeding than

changes in coagulation?

y What is the evidence that volume

restriction is more effective than

correction



Characteristic of Circulation inCharacteristic of Circulation inPatients with CirrhosisPatients with Cirrhosisy Hyperdynamic circulation

High cardiac output

Low peripheral resistance

y

Relatively fluid overloaded Sodium retention

Diminished renal function

Ascites

y Altered blood volume distribution Pooling of blood in the splanchnic circulation

Portal hypertention



CollateralsDilated vessels

High hydrostatic pressure



CollateralsDilated vessels

High hydrostatic pressure

Bleeding



y Every Liver Surgeon can Tell you That

Portal Hypertention is An Important

Determinant of blood loss



Low CVP < 5 mm HgLow CVP < 5 mm Hg

y Anesthesiologists have proved it :

Liverpool UK - M.Johnson , R.Mannar 1998

2 x CVP 9 x Hemorrhage

CVP < 6 mmHg 6 ² 12 mmHg CVP >12 mmHg

303 ml 1259 ml 2703 ml



Since 2008Since 2008

y Preoperative ² we don·t correct verystrictly the PT and aPTT with transfusion

of FFP

y Platelets transfusion-- if Plts< 50 000 andin a case of acute bleeding

y In the phase of dissection ² low CVP

y Fluid Restriction ² very strict balancey Restoration of the blood volume before

reperfusion



Fluid Restriction = Volume ContractionFluid Restriction = Volume Contraction

y Transfusion triger ² Hb<80 g/l

y Transfusion of crystalloids - 4-5 ml/kg/h

y Transfusion of coloids ² max. 10 ml/kg

y Transfusion of FFP = Volume overload

y PCC ² when coagulopathy require quick

reversal without volume overload



Military Medical AcademyMilitary Medical Academy

y April 2007 - August 2010

y 23 liver transplantations

y Average age - 43,7 years

y 18 male , 5 female

Year 2007 2008 2009 2010

Pts 5 4 7 7



ResultsResults -- Blood loss mlBlood loss ml



ResultsResults -- Transfusion of RBC mlTransfusion of RBC ml



ResultsResults -- Reinfusion mlReinfusion ml



PatientsPatients -- Child C in %Child C in %



LT without blood transfusionLT without blood transfusion

Year 2007 2008 2009 2010

Pts 1 (20%) 1 (25%) 5 (71,4%) 5 (71,4%)



ConclusionsConclusions

y Abnormal coagulation tests do notpredict bleeding

y The impaired tests may results in

satisfactory overall hemostatic function

y Preoperative correction of abnormal

coagulation tests with blood product is

ineffectivey In fact it worsens the bleeding tendency



ConclusionsConclusions

y Volume restriction instead of correctionof coagulation tests with large volumes of

FFP is more effective in reducing bleeding

y In cirrhotics, major surgery can be

performed safely without blood product

transfusions ( RBC, FFP, Plts)

OLT Without Blood

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