PowerPoint

Dr. A -

1

von Willebrand (, , .)

Bernard - Soulier syndrome GlanzmannWiskott - Aldrich syndrome Gray platelet Syndrome (-) Quebec (-)Hermansky - Pudlack syndrome (-)Chediak Higashi Syndrome (-)

von Willebrand (, , .)

FVIII (1 : 10.000) FIX (1 : 50.000)FVII1 : 500.000FI, FV, FX, FXI1 : 1.000.000FII, FXIII1 : 2.000.0002 - PAI-1

(3-4%), , von Willebrand (1%) &

&

!

, (, , ), ,, , , 1 -2

(PT)

(aPTT)

, ,

D-dimers

- -

!

&

&

VIII IX XI VII X V II I PTPTT

(Prothrombin Time PT)Quick 1935 &

PPP

PT

VII

(Partial Thromboplastin Time aPTT)1953

&

VIII, IX, XI

von Willebrand aPTT

, V, X PT & aPTT

(Hirudin, Dabigatran)

o

Bothrops snake

PT & PTT

MIXING STUDYNORMAL BLOODFACTOR LEVEL 100%aPTT 28 sec

PATIENT BLOODFACTOR LEVEL 0% aPTT 80 secNOTE: ONLY 30-40% FACTOR REQUIRED FOR NORMAL aPTT

50% PATIENT : 50% NORMALFACTOR LEVEL 50%

aPTT 30 secFACTOR LEVEL 20%

aPTT 50 sec

Diagnosis of Clotting Factor Inhibitors

27

aPTT aPTT aPTT VIII, IX, XI VIII, IX, XI LA

, , 50%

aPTT PT

( Bethesda)

: 0,2 1 / 1.000.000

95%

20%Factor VIII, vW V, IX, XI, XIII , VII, X

, PT PTT von Willebrand

von Willebrand 1%

, PT PTT von Willebrand

von Willebrand 1%

vWF: Ag

RiCof vWF !

, PT PTT Willebrand

Duke Ivy

,

1 PFA 100MultiplateVerify now. . .2 3

Soft keysLCD screenBuilt-In Printer

CarouselCassetteTest Cartridge

(150m) = Closure Time (CT)sec2 :EPI: , ADP: , ADP

PFA - 100

4

high shear rate>5000 /s

capillary 200m

Epinephrine or ADPmembrane withplateletvon Willebrand Factorerythrocyte

FLOW

collagen coating

To: Poujol, Nurden, Paponneau, et al.

lumenfibrinogenplateletcollagen fibrilserythrocytevon Willebrand Factorendothelial cell

PFA - 100

: Willebrand ( 2 & 3), Glanzmann BSS, ASS

: Willebrand ( 1)

PFA - 100 < 80.000/lHt < 30 > 50%

Multiplate

5 & Willebrand

VerifyNow

aggregometer

3 (aspirin, P2Y12 inhibitors, GP IIb/IIIa inhibitors)

,

(10 - 15 )

2 Aggregometer ex vivo, ,

Aggregometer

, , , .. PFA-100

(gold standard) ,

Aggregometer >3

:

, ,

PRP

,

3

(Glanzmanns or Bernard Soulier disease)

(Storage pool disease)

(PT, PTT, vWF, ) F XIII 2-

(Ehlers-Danlos, Rendu-Osler syndrome)

,

,

Point-of-Care-Test (POCT)

,

&

:

-

- ( , )

-

- ( FVIIa, , )

(PT) (PTT)

-

1965Egeberg 1981Griffin C 1984Comp S 1993Dahlback aPC-r1994Bertina V-Leiden1996Poort VIII, IX, XI

Plasminogen Activator Inhibitor (PAI) TFPI MTHFR A1298C

A

CD 55 & CD 59 JAK 2

- - PSA

;

aPC resistance FV Leiden\ G20210A C S III VIII

;

in spite of all efforts, we still do not know a significant part of the thrombosis susceptibility alleles which contribute to the familial thrombosis Bertina 2007 , 15 20%

;

;

II, VII, IX, X PrC, PrS III

15 (;)

AT III

;

VIII Pr S, Pr C & AT III

;

aPCr VIII, vWillebrand, S PAI 1 d-dimer

2

;

VIIIC4b Free Pr S

;VII, VIII, XII, Pr C Pr S, AT III aPCr

;

;To Test Or Not To Test?

2009

2010

;

OXI

;

: - - - -

< 60 , o APS

( )

40 - 60 1

,

(, )

,

(purpura fulminans)

( 60 )

Pr S & Pr C

,

,

(, , )

(, )

- DVT - - - -

77

1,2

1. Baglin T., et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2006; 362:523-5262. Dalen JE., Should patients with venous thromboembolism be screened for thrombophilia? Am J Med 2008; 121:458-4632-3% vs 10% ( 3 ) (> 7 ) (> 6 )

,

1

1

Leiden ( )

2010

( )

( 2012)

1

-

-

- -

transdermal Hormone Replacement Therapy

, (, , .),

F

VIIVIIa

X

+

XaXa

IXa+VIIIa

a

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

F

VIIVIIa

X

+

XaXa

IXa+VIIIa

a

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

F

VIIVIIa

X

+

XaXa

IXa+VIIIa

a

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

5. SEM of a clot, higher magnificationThe clot is a jelly-like mass of fibrin and red blood cells, which is constantly being broken down and rebuilt. The longevity of the clot depends upon the balance between clot formation and fibrinolysis.

VIII IX XI VII X V II I PTPTT

XIIIVIII IX XI VII X V II I PTPTT

vWF PAI

2AP