24 Fazakas Solid OrganTX

8/16/2019 24 Fazakas Solid OrganTX

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S

János Fazakas MD , PhDSemmelweis University

Department of Transplantation and Surgery, Budapest


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1. ABO ( )

– SO = ABO HLA

• L, , ABO

– BM = HLA ABO

2. RBC T: S

– (14 RBC)

•

3. P/P: S

4. P D L /

• O O : → I

• CNI: C I

• R: 12 . ≈ 1 • , 12 B/P


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5. CMV

– CM : , CM

6. T .

–

. ( 4 !)

6. A HLA

– : ,

(HLA I !),

– B ,


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Transfusion and organ transplantation


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L T ( )

• RBC,

• S: 10 RBC, 20 FFP, 8 PL (?)

• L

• : • I AB B, O RBC

RBC ; A O , ABO RBC

• :

• C : , , PA

• RBC RBC

•


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K T

• EPO ESRD• ?

• RIM, SK+ ↑ (1 ≈ 0.5 K)

•

H T

• AD → H

• C (CPB) • M

• P


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* „ FFP and platelets, in the immediate post-transplant period following an ABO-incompatible (ABOi) solid organ transplant”

* „the transfusion risks associated with passenger lymphocyte syndrome (PLS)”

„communication between the clinical team and the transfusion laboratory”

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Use of X-irradiation as an alternative to gamma irradiation (25 Gy but no > 50 Gy)


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• Irradiation to prevent TA-GvHD is not recommended on a routine basis for all

cases• the leuko-reduced products had decreased the Alloimmunization

• ABO and HLA matching has decreased considerably with the use of modern

immunosuppressant drugs• ABO :

()• Preop.: EPO; Intraop.: „cell saver”; Postop.: cell salvage


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„Global”

RECIPIENT

„Vascular bed specific”

GRAFT

Hemostasis view…


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APC

(fast)

AT-III

(slow)

ANTICOAGULATION

T + TM

XII

Kallikrein,

Bradikinin

Plasmin

Plasminogen

Exstrinsic

kinase

Endothel

tPA

FIBRINOLYSIS

Initiation Amplification Propagation

COAGULATION

95 %5 %

XIII

ANTIFIBRINOLYSIS

AGGREGATIONvWF, thrombocyte receptors

ADAMTS13, NO, PGI 2

ANTIAGGREGATION


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H

R C

Saner, FH. Digestion 2013; 88:135–144.

Schaden, E. Curr Opin Crit Care 2013,19:000–000..Northup, PG. Clinical Gastroenterology and Hepatology 2013; 11: 1064-1074.

R R R R

, K

(II, II, I, ), ,

C S, AIII,

P, α2AP,

ADAMS13

LPS, F,F, F III

PA, PAI1

I

200%

D

2570%L →

PC


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H

D

Saner, FH. Digestion 2013; 88:135–144.

Schaden, E. Curr Opin Crit Care 2013,19:000–000..Northup, PG. Clinical Gastroenterology and Hepatology 2013; 11: 1064-1074.

R R R R

, K

(II, II, I, ), ,

C S, AIII,

P, α2AP,

ADAMS13

LPS, F,

F, F III

PA, PAI1

I

200%

D

2570%

L →

PC

B


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PRO

vWF ++++

TF +

TR ++

PAI-1 ++++

ANTI

tPA +

TFPI +++

Heparan +++

TM ++

EC

Crit Care Med 2001; 29 [Suppl.]:S28 –S35

Differential expression

of hemostatic factors

on different endothelial cells

Organ-specific responses by

endothelial cells

Every organ define its hemostasis

according to its function

Vascular bed specific hemostasis


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vWF ++TF +

T ++PAI-1 +

tPA +

TFPI +++Heparan +

TM +

vWF ++TF +

T +PAI-1 +

tPA ++++TFPI +++

Heparan +++

TM +++

vWF absent

TF +

T ++PAI-1 +

tPA +

TFPI +++

Heparan +++TM ++++

Environmental relationship

→ innate immune response

→ prothrombotic effect

Specific anticoagulation and profibrinolysis

Low flow → prothrombotic effect

Secondary hemostasis dependent endothelium

Specifically anticoagulation effect

High flow → anticoagulation effect

Primary hemostasis dependent endothelium


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vWF ++TF +

T ++PAI-1 +

tPA +

TFPI +++Heparan +

TM +

vWF ++TF +

T +PAI-1 +

tPA ++++TFPI +++

Heparan +++

TM +++

vWF absent

TF +

T ++PAI-1 +

tPA +

TFPI +++

Heparan +++TM ++++

Environmental relationship

→ innate immune response

→ prothrombotic effect

Specific anticoagulation and profibrinolysis

Low flow → prothrombotic effect

Secondary hemostasis dependent endothelium

Specifically anticoagulation effect

High flow → anticoagulation effect

Primary hemostasis dependent endothelium


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G =


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• Kidney medulla: vWF ↑↑↑↑↑↑↑↑, TFPI ↓↓↓↓, PC ↓↓↓↓, TM ↓ ↓↓ ↓

vWF +++

TF +TR ++PAI-1 ++

tPA +

TFPI +PC +

TM +

„high flow = anticoagulation” Low flow = IRI = TF ↑ =procoagulation=

microthrombosis

Semin Immunopathol (2012) 34:167–179 Circ Res. 2012;111:110-130

Primary

hemostasis

Secondary

hemostasis

Fibrinolysis

Primary

hemostasis Secondaryhemostasis

Fibrinolysis

Vascular bed specific organ hemostasis


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38 BD → 60% 40% : AT, PC, P, PAP, F12, TAT, D

I .


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G =


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• Liver: vWF absent , TFPI ↑↑↑↑↑↑↑↑, Heparan ↑↑↑↑ ↑↑↑↑ , TM↑ ↑↑ ↑ ↑ ↑↑ ↑ ↑ ↑↑ ↑

vWF absent

TF +TR ++PAI-1 +

tPA +

TFPI +++Heparan +++

TM ++++

Semin Immunopathol (2012) 34:167–179

„low flow = 4 - 8 mmHg”

Circ Res. 2012;111:110-130

Primary

hemostasis Secondaryhemostasis

Fibrinolysis

Vascular bed specific organ hemostasis


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K . 44, 369372 (2012)

S


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⇒⇒⇒⇒ ⇒⇒⇒⇒ ⇒⇒⇒⇒

„Dilution

Consumption

Bleeding”

„No clearance

No synthesis

pH ↓, T°C ↓Consumption”

„hypovolemic”

„Volume

overload”

,, Tsunami ”

,,350-500 ml blood”

= 1 U RBC


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CV ⇒⇒⇒⇒ KVA DAT ⇒⇒⇒⇒ HD (LMWH )

Factor consumption± dilution

,,blood flow: 1-1.5 l/min”

= 1/2 U RBC


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⇒⇒⇒⇒

DBD = + EC ⇒⇒⇒⇒ / + EC/

++++ ====

R

DBD


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Bloodless SOT

Hemodynamic management: avoid „dilution”

Hemostasis management: individualized pyramid of hemostasis

„zero tolerance

for blood loss”


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N = 100% B

H R

P = =


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I = 7590% B

N = 100% B

N

H R P = =


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N = 100% B

A

P↓; IBI 2030% ↓

C

H R P = =


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N = 100% B

R

V +

H R P = =

,, Tsunami ”


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Hemodynamic managementVascular space / blood volume distribution

!


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surgical hemostasis – control of hemorrhage (FXIV)

pH>7.2 se Ca> 1 mmol/l Hgb >100g/l T > 35°C

fibrinogen, thrombocyte - INR, APTI,

- TEG, ROTEM, TAG

fibrinogen

PCC

thrombocyte

FVIIa

FXIII

Tranexam acid

substrate

initiation

amplification

initiation

firmness

Fibr. < 1,5-2 g/L(delivery < 3-3.5 g/L)

FV < 30 % FVII < 30 %Thr < 50-80 G/L

Order of priority

TXA

fibrinolysis

diagnosis

homeostasis

FXIII < 60 %PT < 1.5x

APTI < 1.5x

Fibr(g)=(Fc-Fb)·0.06g·kg

PCC(IU)=(PTc-PTb)·kgFFP(ml)=(PTc-PTb)·1.5ml·kg

Thr(U) = 1U/10kg

off label

> 20 IU/kg

A

P G


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P

C

D !

( )

P C, ,

C

D

I

F

W ?

Individualize the management of hemostasis


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B (BV) = BW × 7090 /P (PT) = BW × 7090 / (1H/100)

C

50 ; 3500 BV; 2100 PV

I


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D

: .

M ?

SAR SOP


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50 ; 3500 BV; 2100 PVHS : 35%R : 25% 1166

FS : 3 /L

R : 1.5 /L

? ?

PS : 60%

R : 40%

3.5 (35%25%)30%

3.5 (2.1 ) (3 1.5)2.75

3.5L (2.1L) (60%40%)2.25

C

I

W

? ?


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BV = VT H () H ()/ H ()B () = B × 7090 /

PV = PT F () F ()/ F ()P (P) = B × 7090 / (1H/100)

PCCRBC FFXIII FVII TATIII

C

F ??

Thr

AT III.

FVII

Fibrinogen

XIII.PCC

RBC

O G I

8401050

1400

1550

1615

2930

1166

1750

2333

2580

2690

4880

1400


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F !

D

V

F = !H

?


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BOL

A12

A24

„focus on the

weakest link”

E OL

....

....

....

....

........

I E

BOL

L

E OL

A12

A

24

S

A

I

HEMOSTATIC THERAP

INDIVIDUALIED

COUNT

PRAMID OF

GRLINGER

J ,


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8888

0000

6666

9999 3333

11110000

4444

11111111

5555

2222

7777

1111 • •

S D S

IC

12121212 24242424

• /, /

• ,

2222 4444

•

() ()

, , , ,

4444

1212121224242424

,

, , ,

666612121212

////

////


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60 %

C

ALF

P

F

PA

30 %

0 %

100 %

R

I G

? A :

A : ↑↑↑↑↑↑↑↑

N

: 12 : 12 : 12 : 12 24 24 24 24

I :

I RBC FFP P


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I RBC, FFP, PL 2014.07.012015.09.30 (=113)

47.1 % NO RBC

82.4 % NO FFP 80.4 % NO P

81.4 % NO CELL SAVER

H OLT 1995 01 05 2015 09 30


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H OLT 1995.01.052015.09.30I RBC (2015.11.10)

I RBC P()M

()M

(%)S

() S(%)

NO RBC 105 7 6,7% 98 93,3%

15 U RBC 285 45 15,8% 240 84,2%

610 U RBC 192 65 33,9% 127 66,1%

1120 U RBC 117 48 41% 69 59,0%

> 20 U RBC 38 26 68,4% 12 31,6%


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Individualized management of hemostasis

!

!


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Mild bloody SOT(1/2 blood volume loss)


Hemostasis management: Fibrinogen + PCC


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Graft preservation solution flushed out = 200 - 300 ml

Hepatic artery / Portal vein anastomosis = 100 ml

Cirrhotic liver removed = 300 - 400 ml

More bleeding as was predicted

by the individualized pyramid

≈≈≈≈ 400 2000 ml

Fibr. < 2-2.5 g/LFV < 30 % FVII < 30 %Thr < 50 80 G/LTXA FXIII < 60 %

PT < 1.5x


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surgical hemostasis – control of hemorrhage (FXIV)

pH>7.2 se Ca> 1 mmol/l Hgb >100g/l T > 35°C

fibrinogen, thrombocyte - INR, APTI,

- TEG, ROTEM, TAG

fibrinogen

PCC

thrombocyte

FVIIa

FXIII

Tranexam acid

substrate

initiation

amplification

initiation

firmness

g(delivery < 3-3.5 g/L)

FV < 30 % FVII < 30 %Thr < 50-80 G/L

Order of priority

TXA

fibrinolysis

diagnosis

homeostasis

FXIII < 60 %APTI < 1.5x

Fibr(g)=(Fc-Fb)·0.06g·kg

PCC(IU)=(PTc-PTb)·kgFFP(ml)=(PTc-PTb)·1.5ml·kg

Thr(U) = 1U/10kg

off label

> 20 IU/kg

A

P G

BV: 100%

BV: 90%10%

BV:80%20%

BV: 70%30%

BV: 60%

40%

BV: 50%50%

BV:30% 70%


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SOT and massive transfusion(1-2-3-4..x blood volume loss)


Hemostasis management: „improved FFP concept” - FFP + Fibrinogen + PCC


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Stainsby D, et al. Br J Haematol 2006, 135:634-641.

„time” and /or „volume”

M ?

M


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M O + PCC + ?

Sorensen B, et al. Critical Care 2011 15:201.

9

7

10

2

T1/2 3-4 h

T1/2 18-30 h

T1/2 38 h

T1/2 48-123 h

A 100%


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surgical hemostasis – control of hemorrhage

(FXIV)

pH>7.2 se Ca> 1 mmol/L Hgb >100g/L T > 35°C

A 100% I

AdaPVed from Prof

substrate

initiation

amplification

initiation

firmness

fibrinolysis

diagnosis

homeostasis

RBC + FFP + T ≠


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1 + 1 + 1= ? !

Sihler KC. Chest 2010; 137(1):20ö-220.

RBC + FFP + T ≠ I

FFP


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FFP

12 radom units of single donor FFP

89 90 90 90

73

88

81

71 68

80 78

85

55

64

87

73

89

69

106

121

110 110

138134

167

145 149

125 125

159

137

159

110116 118

135

0

20

40

60

80

100

120

140

160

180

P T

a P T T

T T

R T F I F I

I F V

F V I I

F V I I I

F I X F X F X

I

F X I I

F X I I I

V W F : R C o

A T I I I

P C

P S

%

PV 100% ?

' ...

O


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: I ' ...

12 consecutive Octaplas batches

98 96 98

93 96

95 96

83

75

90

9692

88

97

83

96 9586

105 105 102 104 104 104108 108

115110

103 105 106 103

120

103 102

111

0

20

40

60

80

100

120

140

160

180

P T

a P T T

T T

R T F I F I

I F V

F V I I

F V I I I

F I X F X F X

I

F X I I

F X I I I

V W F : R C o

A T I I I

P C

P S

%

Bio-pharmaceutical range: ± 20%

Pharmaceutical range: ± 5%

THE PRINCIPLE OF ENRICHED PLASMA


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201278:35868

2 E FFP : + 1 + 500 IU PCC

CRISTALOIDS ARENT USEFUL →→→→ FFP 93% = WATER !

+ 1250 IU FXIII + 100 µµµµ FVII + 500 IU ATIII

The principle of improved FFP


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Blood loss 2x

p p pR R M

Adapted from Prof Görlinger

pH>7.2 se Ca> 1 mmol/L Hgb >70-100g/L T > 35°C

After 5-10U FFP → POCTs / conventional parameters

Fibrinogen

FXIII

Thrombocyte

AT-III

PCC

Fibrinogen 1g →→→→ 2U FFP

PCC 500 IU→→→→ 2U FFP but 5 U Octaplas

FXIII 20IU/kg →→→→ 5U FFP

Thr 1U/10kg

AT-III 500IU→→→→ 5U FFP

diagnosis

homeostasis

The principle of improved FFP


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p p pR R M

Adapted from Prof Görlinger

pH>7.2 se Ca> 1 mmol/L Hgb >70-100g/L T > 35°C

After 5-10U FFP → POCTs / conventional parameters

Fibrinogen

FXIII

Thrombocyte

AT-III

PCC

diagnosis

homeostasis

Fibrinogen 1g →→→→ 2U FFP

PCC 500IU→→→→ 2U FFP

FXIII 20IU/kg →→→→ 5U FFP

Thr 1U/10kg

AT-III 500IU→→→→ 5U FFP

Blood loss 3x

FVIIa

TXA

100-500 µµµµg →→→→ 10U FFP

POC: TEG and ROTEM


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EXTEM CT > 80s

TEG R > 10 min

Normal

Pathologic EXTEM, TEG

Normal


K > 4 min

Alfa angle < 74°

Pathologic FIBTEM

, ,

, MA

MCF

Normal


Normol FIBTEM

K > 4 min

Alfa angle < 74°

MA, MCF

continuously

decrease

TEG/TEM „slides back”

Factors replacement ?

TEG/TEM „became thiner”

„ substrate: platelets ↓ ”

EG/EM

„ substrate: fibrinogen ↓ ”

TEG/TEM „the end … run out”

Fibrinolysis ?

f t t t t ?


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yours factor concentrates run out ?

Targeted replacement of factor concentratesor give FFP but remove water (CVVH)

400 30 / FFP 400 →→→→


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5. :

Topical versus systemic hemostasis

„ TOPICAL ”


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• „Most at risk” organ: the others

• „Weakest” organ:The liver graft

• The solution:

topical administration of „fibrinogen”

R : T : + :


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Topical application of fibrinogen powder and Tachosil®®®®

Graftectomy →→→→ failed local hemostasis (antiplatelet therapy.)

→→→→ bleeding &&&& hematoma

T i l li ti f fib i PCC d


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Topical application of fibrinogen - PCC powder

KT 2003, AMI 2012 BMS 1150!, 1100

40


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Hgb 106 g/L

Htc 31 %

Prothrombin 56%AT-III 102,9%

INR 1,4

V 72%

VII 84%

X 118%

aPTI 36,6 sFibrinogen 7,4 g/L

Thr 226 G/L

D-dimer > 4850 ug/L

ACT 105

40

P, TT →→→→ ?


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Hgb 106 g/L

Htk 31 %

Prothrombin 56%AT-III 102,9%

INR 1,4

V 72%

VII 84%

X 118%

aPTI 36,6 sFibrinogén 7,4 g/L

Thr 226 G/L

D-dimer > 4850 ug/L

ACT 105s;

100 N®®®®

T


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Medical history,

Clinical picture

Conventional lab parameters

POC: ROTEM/TEG, Multiplate

Invidualiazed pyramid of Görlinger

„The weakest” organ„Most at risk” organ

T / S

Don’t harm, don’t treat numbers

Improved FFP: fibrinogen-PCC-ATIII-FXIII

Replace only what is missing

Minimal Models for Quantum Decoherence in


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Coupled Biomolecules

Energy transfer.

Reaction time, dynamics,

coherent, incoherent, localized

Why should medical doctors be interested in

quantum biology/pathophysiology?


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Quantum mechanics plays a

critical role in much of biology!

• Green Fluorescent Protein used in diagnosis

– Highly efficient marker plastic surgery

quantum biology/pathophysiology?

• Retinal, responsible for vision – Ultrafast vision receptor

• „ Tunneling in enzymes”

– RBC, PLT, Coagulation

factorsthe future ?

C QW ?

T !


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@.

R

½ - 3/4 vércseréig = FAKTOROK

> ¾… 3-4 x vércsere: FAKTOROK + FFP

Blood loss < predicted by the

½ - 3/4 Blood volume loss = FACTOR CONC.

Massive transfusion = FACTOR CONC. + FFP

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24 Fazakas Solid OrganTX