J Fazakas Bleeding Management in Organ Transplantation

8/2/2019 J Fazakas Bleeding Management in Organ Transplantation

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Bleeding management in organBleeding management in organ

transplantation and intensive caretransplantation and intensive care

Bleeding Management Course - from theory to clinical practice

Jnos Fazakas MD, PhD


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THE COMPLEXITY OF PERIOPERATIVECOAGULATION DISORDERS

loss

dilution

hyperfibrinolysis

consumption

supply

endogen

heparinoids

one organ failure multiorgan dysfunction


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Kidney transplantation: hemodialysis + anticoagulation

venous and arterial reperfusion: coagulation disorder


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Pancreas and kidney transplantation: hemodialysis + anticoagulation , DM + IHD

2 grafts 2 x venous + arterial reperfusions:

coagulation disorder, fibrinolysis


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Kidney recipients: catheter associated thrombosis and stenosis, atrial fibrillation,

coronary stents, congenital coagulation disorders

treatment with vitamin K antagonist INR 2.5-5.5

TACO

TRALI ?

CIT + 2-4 hours HDF

PCC

Clinical Practice Guidelines and Clinical Practice Recommendations, 2006 Updates


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In patients who are receiving VKAs and require reversal of the

anticoagulant effect for an urgent surgical or other invasive procedure, the

guideline developers recommend treatment with low-dose (2.5 to 5.0

mg) IV or oral vitamin K (Grade 1C).

For more immediate reversal of the anticoagulant effect,

the guideline developers suggest treatment with fresh-frozen

plasma or anotherprothrombin concentrate in addition to

low-dose IV or oral vitamin K (Grade 2C).

The perioperative management ofantithrombotic therapy

American College of Chest Physicians, evidence-based clinical practice guideline

(8th edition)

Chest, 2008 Jun; 133 (6 Suppl) : 299S-339S


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patients No RBC RBC FFP PLTCoagulation

monitoring

Dalmau et al. 2001 122 34 % 2.9 (0-6) 1.6 (0-4) 7.9 (0-15) BT, TEG

Dalmau et al. 2004 127 38 % 2.3 (0-5) 1.25 (0-3) 5 (0-11) BT

Massicote et al. 2005 206 32 % 2.8 (0-7) 4.1 (0-8) 0.4 (0-3) ?

Frasco et al. 2005 69 ? 2.9 (0-6) 2.5 (0-5) 1.2 (0-2) ?

Mangus et al. 2007 526 17.5 % 3 7 6 ?

Boer et al. 2008 236 26 % 2.2 (0-6) 2 (0-7) 0 (0-1) BT, TEG

Massicote et al. 2008 200 81.5 % 0.3 0.8 0 0 ?

Overview of blood product transfusion

during liver transplantation

Curr Opin Organ Transplant 14 (2009) 286-290

Clear reduction of blood products requirements

Blood tests (BT) usefulness in bleeding prediction

20% no bleeding, 20% still serious bleeding

Clear reduction of blood products requirements

Blood tests (BT) usefulness in bleeding prediction

20% no bleeding, 20% still serious bleeding


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Hepatectomy: preop. coagulation profile coagulation factors : dilution + consumption

blood loss correlate with the degree of surgical difficulty

adhesion dissection and transection of portocaval shunts


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Hepatectomy: preop. coagulation profile coagulation factors : dilution + consumption

blood loss correlate with the degree of surgical difficulty

adhesion dissection and transection of portocaval shunts


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Anhepatic phase : no clearance of activated coagulation factors and tPA

no supply by synthesis activity but a continuous consumption

failure of homeostasis: pH , Se Ca+ , TC

volume overload in the splanchnic area


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Venous and arterial reperfusion: coagulopathy and microvascular diffuse bleeding (30-90 min)

endogen heparinoids ; fibrinolitic substances

the degree and duration is variable with donor graft quality


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core

skin

relative normovolemiaincreased CVP

Limbs: venous blood shiftin the abdominal and thoracic vein

Intraoperative hypothermia

Warming


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Coagulation

Hypothermia

fibrinogen

prothrombin complex

thrombocyte

Normothermia

FFP (factor VIII !!!!)

Fibrinolysis

EAC, tranexamic acid

New possibility:

rFVIIa, XIIIa


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amplification

TF VIIa

XaIIa

PLT

Ia

VIIIa

Va

IXa

XIIIa

20 x

5% 95%

Coagulation tests

Y shape modell - 1960 cell based modell - 1980

standard

testsTEG

Thrombin production

initiation propagation


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INR kva WHO etalon KVA: K vitamin antagonist blood

(PT test / PT normal)ISI

kva

Tripodi et al. Hepatology, 2007, 46: 520-27; Bellest et al. Hepatology, 2007, 46:528-34

INRkva

A-B=0.3

C=0.5

healthy test


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INR liver etalon blood of cirrhotic patient

(PT test / PT normal)ISI

liver

Tripodi et al. Hepatology, 2007, 46: 520-27; Bellest et al. Hepatology, 2007, 46:528-34

INRliver

A-B=0.01

C=0.02


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platelets provided phospholipid surface to complement normal thrombin generation

Tripodi et al. Hepatology, 2007, 46: 727-733

Evidence of normal thrombin generation in cirrhosisdespite abnormal conventional coagulation tests


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Balance of potential risks and benefits ofplatelets in liver transplantation

Platelets in liver transplantation: Friend or foe?

BenefitsBenefits RiskRisk

Component of primary hemostasisContribution to ischemia reperfusion

injury

Involvement in tissue repair Involvement in postoperative thrombosis

Involvement in liver generationAssociation with adverse outcome of

transplantation

Liver Transpl, 2008, 14: 923-931

Chest, 2008 Jun; 133 (6 Suppl) : 299S-339S

For patients receiving aspirin, clopidogrel, or both, are undergoing surgeryand have excessive or life-threatening perioperative bleeding, the guideline

developers suggest transfusion of platelets or administration of otherprohemostatic agents (Grade 2C).

The perioperative management of antithrombotic therapy. American College of ChestPhysicians evidence-based clinical practice guidelines (8th edition).


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surgical hemostasis

pH>7,2 SeCa> 1 HGB>100g/l T> 35TEG, fibrinolysis, aprotinin ?

fibrinogen

PCC , FFP

PLT

VII a

1) factor dilution

2) VIII , vonW syndr.

3) G 2a/3b receptor number

4) fibrin polymerization

trouble

Female, HLA DR

TRALI / TACO

FFP

Fibrinogen < 1g/l V < 20% VII < 20% PLT < 50.000

initiation amplification - propagation

normothermia ?hypothermia ?

XIIIa


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Antibody against fathers leukocyte HLA

75% of female blood donors were pregnant

Appearance of HLA antibody :

in all female donors: 15 %

in never pregnant donors: 1.6 %

after 1 pregnancy: 10.5 %

after 2 pregnancies: 15.8 %

after 3 pregnancies: 25 %

after 4 pregnancies: 36 %

Odds ratio of TRALI

all plasma 3.4 (1.2-10.2)

male plasma 2.7 (0.7-10.1) female plasma 25.6 (1.3- 49.9)

Massicote et al: Transplantation 2008 Apr 15;85(7):956-962 Rana et al. Transfusion 2006; 46:1478-83

Massicote, 2008: The avoidance of plasma transfusion was associatedwith a decrease in RBC transfusions during liver transplantation.


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12 - 18 hours

4 - 6 hours

> 24 hours

healthy

Nature Medicine 2007,13: 463 469


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O2 supply

CPAP mask

SPIROMETRY TESTING AFTER LTX

MINOR TRALI


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Components (n)Class I

n (%)

Class II

n (%)

Class I & II

n (%)

Total

n (%)

RBCs (106) 7 (6.6%) 8 (7.5%) 3 (2.8%) 18 (16.9%)

Cryo (66) 3 (4.5%) 3 (4.5%) 10 (15.1%) 16 (24.2%)

FFP (77)9

(11.6%)4 (5.2%) 9 (11.6%) 22 (28.5%)

Platelets (59) 7 (12%) 5 (9%) 1 (2%) 13 (22%)

HLA antibodies in blood componentsUnappreciated risk factors for transplant patients

Human Immunology 65 (2004) 240-244

no published data: HLA antibodies promote allograft dysfunction ?!?

transfusion mediated rejection: HLA-Ag graft + antibodies HLA-Ab


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0

2

4

6

Anesthe

sia

hepa

tectom

y

hepa

tectom

y

anhepa

tic

PVreperfusi

on

Artreperfusi

on

Endof

surgery

POP1ho

ur

0

10

Prepare for anhepatic phase Optimize all function

Responsiveness !

AT III

fibrinolysis Endogeneousheparinoids


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The two tales of coagulation in transplantation:the rebalancing story

Normal patient Patient with liver disease

thrombocytopenia + function defects

enhanced NO + PGI2 production

Primary hemostasis

Delicate rebalancePromoting bleeding Promoting thrombosis

elevated levels of VWF

decreased levels of ADAMTS

(VWF protease)

Secondary hemostasis low level of II, V, VII, IX, X, XI factors

dysfibrinogenemia

elevated levels of VIII factor

decreased levels of prot C, prot S, AT III

decreased levels of heparin cofactors

Fibrinolysis low levels of 2antiplasmin,XIII factor

elevated tPA levels

low levels of plasminogen

Current Opinion in Organ Transplantation 2008, 13: 298-303


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Hypercoagulability based on TEG

short R time < 4 min, increased angle (> 75), increased MA > 75 mm

Hypercoagulable Normal


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ESDL etiology and coagulation profilePLT, INR, APTI, coagulation factors ATIII, protein S, protein C

Plasminogen, t PA, PAI 1, PAI 2 2-antiplasmin, 2 -macroglobulin

Risk of thrombosis

Budd Chiari syndr., POPH,glycogen storage disease,

AIH, PSC, PBC

More AT III (Na Heparin) thanfibrinogen, PCC, platelets, FFP

Normothermia

YesYes GRAFT quality

Risk of bleeding

Wilsons d., HCV, HBV,ALD, hemochromatosis

NASH

Hypothermia

volume restriction

fibrinogen, PCC,

platelets, FFP fibrinogen, PCC,

platelets, FFP

TEGTEGTEGTEG

Poor quality graft

TEGTEGGood quality graft

Fibrinolysis

Heparin like effect

Diffuse bleeding

Reperfusion

Fibrinolysis

Heparin like effect

15-30 min

R, K time MA / MCF


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Anticoagulationgylcocalyx the endothelial gatekeeper

Physiologic factors: protein C, protein S, AT III

Level must be measured and corrected

Graft glycocalyx is burned out after reperfusion

AT III, Na Heparin, LMWH, platelet inhibitors /adv. vs disadv./

According to vascular anastomosis

According to surgical field (wet or dry) According to patient comorbidities

According to coagulation parameters measured

National and local protocols

pediatric pts. more vulnerable

Patient tailoredcoagulation profile

AT III


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Documents

J Fazakas Bleeding Management in Organ Transplantation