Sri S Adiyanti-Clinical Pathology

HEMOSTASIS
Hemostasis

body mechanism
to stop traumatic bleeding
to prevent spontaneous bleeding
to keep the fluidity of blood
 Reactions in hemostatic process

 Vascular reaction
primary hemostatic
barrier
 Cellular reaction
 Biochemical reaction / secondary
hemostatic barrier
 The role of vascular in
hemostasis
 vaso constriction
 Stimulates coagulation factors and platelets
 Substances synthesized by endothelial cells:
 von Willebrand factor
 tissue plasminogen activator (t-PA)
 plasminogen activator inhibitor -1 (PAI-1)
 prostacyclin (PGI2)
 Thrombomodulin (PC activation)
 Glycosaminoglycan (heparan sulphate, dermatan
sulphate)
Platelet

 Originated from cytoplasm of megakariocyte

(fragmentation)
 Morphology : discoid, biconvex, Ǿ 2 – 4 μm
 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)
 The Platelets

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
Morphology of platelet
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 a granule and
dense granule)
 Stabilization of the plug : platelet factor 3 (flip
flop of membrane phospholipid)
Platelet Function
 phospholipid

Phospholipase A2, C

Arachidonic acid

cyclooxygenase Aspirin

PGG2, PGH2
PGI2 Thromboxan
synthetase synthetase

Prostacyclin Thromboxan A2
 Coagulation Factors

Factor I Fibrinogen precursor of fibrin

Factor II Prothrombin serine protease
Factor III Tissue thrombo initiate extrinsic path.
plastin
Factor IV Calsium ion bridge between
Gla - phospholipid
Factor V ProaccelerinCofactor of Xa
Factor VII Proconvertin serine protease
Factor VIII Anti hemophilic f. Cofactor of IXa
 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.
Vitamin K

 Vit. K is required for carboxylation of glutamic

acid → g 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)
 Precursor of
II, VII, IX, X
Residue
Glutamic acid
(GLU) Vitamin KH2

carboxylase

Vitamin K
Residue epoxide
g Carboxy glutamat Oral
(GLA) Anticoagulant

Prothrombin
VII, IX, X
 Negative surface Tissue thromboplastin
Kal. PK
HMWK
XII XIIa

XI XIa VIIa VII

IX IXa
Ca++
Pf 3 Ca++
VIII VIIIa

X Xa
Ca++
Pf3
V F1.2Va Fibrinogen
+
Prothrombin Thrombin FPA
Fibrin monomer +
FPB

Fibrin polimer
XIII XIIIa
Homeostatic mechanism

 Local: fibrin, blood flow

 Humoral:
- Antithrombin
- Protein C
- Protein S
- Heparin cofactor II
- TFPI
 Cellular : liver cell, RES
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
Function of antithrombin
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.
Protein C pathway
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
Mechanism of action of TFPI
 Contact activation

XIa

IXa + VIII APC

TF-VIIa Xa+V IIa Fibrin

Fibrinolysis
TFPI TM
TAFI
T
FIBRINOLYTIC
SYSTEM
 Fibrinolytic system

 Fibrinolysis is a physiologic response to the

deposition of intra or extra vascular fibrin
 Function : to destroy fibrin by enzymatic process
 Consist of :
 Plasminogen
 Plasminogen Activator
 Inhibitor
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
 Plasminogen activator
Physiologic plasminogen activators:
 Tissue-type plasminogen activator (t-PA)
 Urinary- type plasminogen activator (u-PA)
Contact-phase dependent activators: F XIIa,
Kallikrein
Exogen:
 Streptokinase (SK)
 Staphylokinase (SAK)
 Vampire bat plasminogen activator
Inhibitor of fibrinolysis system

Antiplasmin: Plasminogen activator

 a2 plasmin inhibitor
inhibitor
 PAI-1
 a2 macroglobulin
 PAI-2
 antithrombin  PAI-3 (?)
 a1 antitrypsin
 TAFI
 Transamin
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 -
Coagulation and Fibrinolytic
cascade
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