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Hemostasis

http://upload.wikimedia.org/wikipedia/commons/e/e6/Bleeding_finger.jpg

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Platelet

Originated from cytoplasm of megakariocyte

(fragmentation)

Morphology : discoid, biconvex, 24 m

Cytoplasm contains:

a-granule (PF4, b-thromboglobulin, platelet

derived growth factor, vWF, fibrinogen, F V)

Dense granule (Ca, ADP, ATP) Membrane: phospholipid bilayer, glycoprotein

(receptor)

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Megakaryoblast Megakaryocytes Platelets

1/3 of platelets: stored in spleen

2/3 of plateletes: blood circulation

half-lime 3-4 days

15% use daily for haemostasis

normal platelet count 140-360 x 109/l

The Platelets

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Morphology of platelet

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The role of platelet in hemostasis

Platelet plug formation:

Platelet adherent (need von Willebrand Factor)

Platelet aggregation stimulated by ADP, thrombin,

thromboxan A2, epinephrine, collagen Platelet release reaction (from agranule and

dense granule)

Stabilization of the plug : platelet factor 3 (flip flop of

membrane phospholipid)

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phospholipid

Arachidonic acid

PGG2, PGH2

Thromboxan A2

Phospholipase A2, C

cyclooxygenase

Thromboxan

synthetase

Aspirin

Prostacyclin

PGI2

synthetase

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Coagulation Factors

Factor I Fibrinogen precursor of fibrin

Factor II Prothrombin serine protease

Factor III Tissue thrombo initiate extrinsic path.

plastinFactor IV Calsium ion bridge between

Gla - phospholipid

Factor V Proaccelerin Cofactor of Xa

Factor VII Proconvertin serine protease

Factor VIII Anti hemophilic f. Cofactor of IXa

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Coagulation factors (cont)

Factor IX Christmas factor serine protease

Factor X Stuart Prower factor serine protease

Factor XI Antihemophilic C serine protease

Factor XII Hageman factor serine protease

Factor XIII Fibrin stabilizing f. transglutaminase

Prekallikrein Fletcher factor serine protease

HMW kininogen Fitzgerald factor cofactor of Kall.

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Vitamin K

Vit. K is required for carboxylation of glutamic

acid carboxy glutamate

Vitamin K dependent protein : prothrombin,

VII, IX, X, protein C, protein S, protein Z

Deficiency of vit. K PIVKA (protein induced

by vitamin K absence or antagonist)

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Residue

Glutamic acid

(GLU)

Precursor of

II, VII, IX, X

Prothrombin

VII, IX, X

Residue

gCarboxy glutamat

(GLA)

carboxylase

Vitamin KH2

Vitamin K

epoxide

Oral

Anticoagulant

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Negative surface Tissue thromboplastin

Kal. PK

HMWK

XII XIIa

XI XIa VIIa VII

IX IXa

Ca++

Pf 3

VIII VIIIa

X Xa

Ca++

Pf3

V Va Fibrinogen

Prothrombin Thrombin

Fibrin monomer

Fibrin polimer

XIII XIIIa

Stabilized fibrin

Ca++

FPA

FPB+

F1.2

+

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Homeostatic mechanism

Local: fibrin, blood flow

Humoral:

- Antithrombin

- Protein C- Protein S

- Heparin cofactor II

- TFPI

Cellular : liver cell, RES

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Antithrombin

Synthesized in the liver

Function : neutralize thrombin and other

serine protease (XIIa, XIa, Xa, IXa, VIIa,

Kallikrein,plasmin)

Heparin cofactor

Activities enhanced by heparin

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Function of antithrombin

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Protein C and protein S

Both are vitamin K dependent protein

Thrombin with thrombomodulin as cofactor

activates Protein C activated Protein C(APC)

APC with Protein S as cofactor inactivates F Va

and F VIIIa.

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Protein C pathway

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Tissue factor pathway inhibitor

(TFPI)

Function : inhibit F Xa and F VIIa

Mechanism of action:

First F Xa + TFPI F Xa-TFPI complex

F Xa-TFPI complex + F VIIa-TF complex

quartener complexed

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Mechanism of action of TFPI

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Fibrinolytic system

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Fibrinolytic system

Fibrinolysis is a physiologic response to thedeposition of intra or extra vascular fibrin

Function : to destroy fibrin by enzymatic process

Consist of : Plasminogen

Plasminogen Activator

Inhibitor

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Fibrinolytic system

Plasmin : proteolytic enzyme, substrates :

fibrin, fibrinogen, V, VIII, hormon, complement

PLasminogen : proenzyme of plasmin, found in

plasma and other body fluid

Plasminogen activator

Inhibitor

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Plasminogen activator

Physiologic plasminogen activators: Tissue-type plasminogen activator (t-PA)

Urinary- type plasminogen activator (u-PA)

Contact-phase dependent activators: F XIIa, KallikreinExogen:

Streptokinase (SK)

Staphylokinase (SAK) Vampire bat plasminogen activator

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Inhibitor of fibrinolysis system

Antiplasmin:

2plasmin inhibitor

2macroglobulin

antithrombin

1antitrypsin

TAFI

Transamin

Plasminogen activator

inhibitor

PAI-1

PAI-2

PAI-3 (?)

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Coagulation and Fibrinolytic cascade

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Plasminogen Free plasminogen

in clot

PAI

Plasminogen activator

Plasmin Free plasmin antiplasmin

in clot

Fibrin FDP Fibrinogen FDP

D dimer + F V, F VIII D dimer -

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Contact activation

XIa

IXa + VIII APC

TM

TF-VIIa Xa+V IIa Fibrin

Fibrinolysis

TFPI TM

TAFI

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