Rika Nilapsari dr.

SpPK
Hemostasis

Is the complex process by which the bo

dy spontaneously stop bleeding and m
aintains blood in the fluid state within
the vascular compartment
 Hemostatic system :

To maintain a complete balance

of the body’s tendency toward cl
otting and bleeding

Bleeding Clotting

Hemostasis
Hemostasis can be divided into 2 stages :
Primary Hemostasis :
Platelet adhesion to exposed collage
n within the endothelium of the vess
el wall

Secondary Hemostasis :
Enzymatic activation of the coagulatio
n proteins to produce fibrin from fibrin
ogen  stabilizing fragile clot formed
during primary hemostasis
Hemostasis is achieved by highly
integrated and regulated interaction of

• Blood vessels
(Vascular system)
• Platelets
• Coagulation proteins
• Fibrinolysis
Endothelial Cells Basement Membrane

Red Blood Cells Platelets White Cells

Structure of the vessel wall :
outermost layer ( t. adventitia)
middle layer (t. media)
inner layer ( t. intima)
When endothelial lining is disrupted vas
cular system act to prevent bleeding:

• Rapid vasoconstriction
• Diversion of blood flow
• Initiation of contact activation of
platelets
• Contact activation of coaagulation
system
 What are Platelets?
Disk-shaped “cells”
produced in the megakaryoc
ytes of Mature Platel
the bone marrow et

Megakaryocyte

Bone
Marrow
Platelets :
• 2-4 μm in diameter
• Quantity : 150.000 – 350.000 / μL
• Life span : 7-10 days in circulation
 Anatomy of a Platelet
Dense Body
Dense Tubular System
ADP Serotonin
ATP Calcium
phosphates
Microtubular System

Plasma Membrane
PF3
Glycogen

Exterior Coat
Alpha Granules (Glycocalyx)
PF4 Fibrinogen
Factor V Fibronectin Mitochondria
Factor VIII R:ag ß Thromboglobulin
(vWF) PDGF, thrombospondin
Surface
Cytosol Connecting System
Factor XIII
Peripheral zone (receptor/stimulus region)
• Glycocalix
• Platelet membrane
• OCS
• Submembranous region

Sol-gel zone (cytosceletal /contractile region)

• Microtubules : tubulin
maintaining discoid shape
• Microfilaments : Thrombosthenin
capable of contraction
Orgenelle zone ( metabolic region)
• Granules :
α granules
Dense granules
Lysosomes
Glycogen granules

• Mitochondria
• Dense tubular system
• Peroxisome
Storage and Circulation

33%
pooling
67%
in the
circulation

Spleen
Megakaryocy
te
 Platelet participate in hemostasis by :
• Providing a negatively charged
phospholipid surface for factor X &
prothrombin activation

• Release of substances that mediate

vasoconstriction, platelet aggregation,
coagulation (thrombin generation),&
vascular repair

• Providing surface membrane glycoprot.

such as GPIb & IIIa to attach to other
platelet via fibrinogen.
 Platelet Function
Adhesion A
ADP
Shape Chan Release
ge Release
3 seconds

Aggregation B

10 seconds

Coagulation C

Fibrin
Formation 5 minutes
 Platelet adhesion

The principle mechanism of platelet adhe

sion involves :
– Plasma
– Collagen fibres
– Platelet membrane glycoprotein GPIb
(the receptor for von Willebrand’s fact
or/vWF)
 Coagulation Factors

I FIBRINOGEN
II PROTHROMBIN
III THROMBOPLASTIN = TISSUE FACTOR
IV CALSIUM
V PROACCELERIN, LABILE FACTOR
VI -
VII SERUM PROTHOMBIN CONVERSION ACCELERATOR (SPCA),
STABLE FACTOR
VIII ANTIHEMOPHILIC FACTOR ( AHF )
IX CHRISTMAS FACTOR, PLASMA THROMBOPLASTIN
COMPONENT (PTC)
X STUART FACTOR, STUART POWER FACTOR
XI PLASMA THROMBOPLASTIN ANTECEDENT (PTA)
XII HAGEHEMAN FAKTOR
XIII FIBRIN STABILIZING FACTOR
Classifications of coagulation factors
by hemostatic function

Substrate
Fibrinogen (F I)
Cofactors
Labile factor (F V)
F VIII C
Enzymes
Serine protease : IIa,VIIa,IXa,X
a,XIa,prekalikrein
Transminase : F XIIIa
 Classifications of coagulation factors
by physical properties

Fibrinogen Group
Factors I, V, VIII & XIII
Prothrombin Group
Factors II, VII, IX & X
Contact Group
– Factors XI, XII
– Prekallikrein (Fletcher Factor)
– High Molecular Weight Kininogen (
Fitzgerald Factor)
Blood coagulation leading to fibrin f
ormation can be separated into three
pathways :

Extrinsic pathway
Intrinsic pathway
Common pathway
 INTRINSIC EXTRINSIC

ACTIVE SURFACE PREKALLIKREIN VII

PLASMIN
HMWK
XII XIIa XIIf
Ca++
HMWK HMWK
KALLIKREIN
XI XIa VIIa
TISSUE FACTOR
IX IXa Ca+++
Ca++
P+f3 F VIII
Ca++
(IIa Pf3 Ca++ VIII) (VII/VIIa Ca++ TISSUE FACTOR)

X Xa COMMON
Ca++
V+
P+f3
Ca++
(Xa –V-Pf3 Ca++)
(PROTHROMBINASE)
FIBRINOGEN
PROTHROMBIN THROMBIN

FIBRIMONOMER + PEPTIDES
Ca++
SOLUBLEFIBRIN
XIII Ca++ XIIIa Ca++

STABILIZED FIBRIN
 INHIBITOR COAGULATION
- ANTI THROMBIN III
- PROTEIN C

 AT III BLOCK AT III : XIIa, XI a, IX a, Xa, IIa

 PROTEIN C BLOCK : VIII : C, Va
Fibrinolysis :

The physiologic process of re

moving unwanted fibrin dep
osits
 SISTEM FIBRINOLISIS
ENDOTHELIUM

PLASMA ACTIVATOR JARINGAN LAIN

- F XIIa
- KALLIKREIN
FIBRIN BOUND BOUND “PHYSIOLOGIC”
FORMATION PLASMINOGEN PLASMIN PROTEOLYSIS
(FIBRIN) (FIBRIN) (FIBRINOLYSIS)

PLASMINOGEN

FREE FREE “PATHOLOGIC”

PLASMINOGEN PLASMIN PROTEOLYSIS
(PLASMA) (PLASMA) (FIBRINOLYSIS)

ANTIPLASMIN - α2 ANTI PLASMIN

INHIBITOR - α2 MACROGLOBULIN
(PLASMA)
- α1 ANTI TRIPSIN
• Most common cause of death in the
world.
• Thrombosis (arterial & venous) is pr
oduced by a shift in the balance bet
ween Thrombin Generating Mechan
isms (Clot Formation) and Plasmin
Generating Mechanisms (Clot lysing
)
 Thrombosis

Clot
lysing

Clot form
ation

Balance
 Pathogenesis : (Virchow triad)

1. Endothelial injury

2. Alterations in normal blood flow

- stasis
- turbulence

3. Hypercoagulability
 Red (fibrin) vs White (platelet) clots

• The structure of a thrombus varies with the vess

el in which it is located.
 In a high-flow arterial vessels, platelet thrombi
are seen. These macroscopic aggregates of platel
ets have a white appearance (white thrombi)
 In low-flow vessels (veins), the initial platelet pl
ug, which may have started the thrombus, is oft
en not detected. These clots results from the accu
mulation of red blood cells in fibrin strands and
are called Red Thrombi.
 Usually occlusive
Most common site are coronary, cereb
ral and femoral arteries
When arterial thrombus arise in heart
chamber of aortic lumen  mural thro
mbi
The thrombi tipically are firmliy adhe
rent to the injury arterial wall
Gray-white
Composed platelets>>, fibrin, erythocy
tes and degeneratif leucosites
Risk factor :

Hypertension
Hypercholesterol
Hyperlipoprotenemia
Smoking
DM
Hyperhomocysteinemia
Polycitemia
 slowly moving
contain more erytrocyte
90% cases affect the veins of lower ext
remities
Deep venous thrombosis may occur wi
th stasis and hypercoagulable states
Risk factor :

Immobilization
Surgery
Malignancy
Pregnancy
Contraception
AT III def.
Protein C def.
protein S def.