2. Haemostasis
Process of formation of hemosatic plug to halt
bleeding & restore normal blood flow.
Hemostasis is a precisely orchestrated
process involving platelets, clotting factors,
and endothelium that occurs at the site of
vascular injury and culminates in the
formation of a blood clot, which serves to
prevent or limit the extent of bleeding.
3. Component of Hemostatic System
Vessel wall-Endothelial cells & subendothelial
extracellular matrix i.e. collagen
Platelets
Coagulation system -coagulation factors &
coagulation inhibitors
Fibrinolytic system
8. Clot stabilization and resorption.
Polymerized fibrin and platelet aggregates
undergo contraction to form a solid, permanent
plug that prevents further hemorrhage.
At this stage, counterregulatory mechanisms are
set into motion that limit clotting to the site of
injury and eventually lead to clot resorption and
tissue repair.
9.
10. Role of platelet in hemostasis
Forming the primary plug that initially seals
vascular defects and by providing a surface that
binds and concentrates activated coagulation
factors.
11. Platelet adhesion {Subendothelium—VWF—GPIb
receptor on platelet}
Shape change (from round disc to flat plate with multiple
spiky protrusion)
Release reaction from alpha (Fibrinogen, Factor V,
Fibronectin, Platelet factor 4, PDGF, TGF-beta) & dense
granules (ADP, ATP, Calcium ions, Serotonin,
epinphrine)
Platelet aggregation {through platelet GPIIb-IIIa receptor binding to
fibrinogen & form primary haemostatic plug}
Platelets
12.
13. Coagulation cascade
series of amplifying enzymatic reactions that lead
to the deposition of an insoluble fibrin clot –
secondary hemostatic plug
18. Coagulation normally is restricted to sites of vascular
injury by:
Coagulation factors present in inactivated forms require
enzymatic activation
Circulating inhibitors of coagulation factors, such as
antithrombin III, whose activity is augmented by heparin-like
molecules expressed on endothelial cells
Expression of thrombomodulin on normal endothelial cells,
which binds thrombin and converts it to an anticoagulant
Activation of fibrinolytic pathways (e.g., by association of t-
PA with fibrin
19. Role of endothelium
Has both prothrombotic and antithrombotic
properties.
Antithrombotic properties are divided into :
Platelet inhibitory effect: intact endothelium act as
a barrier prevents binding of platelet with vWF &
collagen. Release PGI2 & NO
Anticoagulant effects: exert via expression of
various molecules like thrombomodulin, heparin
like molecule, TFPI
Fibrinolytic effect-
20.
21. Basic function of HAEMOSTATIC
system
The haemostatic mechanisms have 2 primary
functions:
1. To promote local haemostasis at the site of injured
blood vessel.
2. To ensure that the circulating blood remains in
fluid state while in the vascular bed i.e. to prevent the
occurrence of generalised thrombosis.
22. Why Bleeding disorders?
Failure of normal haemostatic mechanism.
o Injury to vascular endothelium
o Platelets defects
o Coagulation defects
o Fibrinolytic system defects
o Combination of all these
23. What are Bleeding disorders
• Group of disorders of diverse aetiology,
characterised by abnormal tendency to bleed
either spontaneously or after slight trauma.
24. Accordingly, there are specific tests for
assessing each of these components:
A. Blood vessel wall: Tests for disordered vascular
haemostasis
B. Platelets: Tests for platelets and their functions
C. Plasma coagulation factors: Tests for
blood coagulation
D. Fibrinolytic system: Tests or fibrinolysis
E. Inhibitors: Tests for coagulation inhibitors
25. Basic approach of bleeding disorder
Comprehensive clinical
examination
Screening tests
Specific tests
then
•Patient’s clinical history
•Family history
•Details of site of bleeding
•Frequency of bleeding
•Character of haemostatic
defect
26. History s/o bleeding disorder:
Spontaneous bleeding.
Bleeding from more than one site
Recurrent episodes of bleeding .
Severe bleeding from trivial trauma.
Excessive bleeding following Sx procedures like tooth
extraction & tonsillectomy.
Spontaneous haemarthrosis or deep hematoma
formation.
Recurrent epistaxis without seasonal variation
Menorrhagia
H/O taking drugs & nutritional supplements like aspirin,
garlic, ginger exacerbate bleeding.
27. INHERITED DISORDERS ACQUIRED DISORDERS
Early age of presentation
Family history positive
More severe
Bleeding is the dominant
feature
Single factor defect
Later age of presentation
Family history usually negative
Less severe
Clinical picture is dominated by
the underlying disorder e.g.DIC
Multiple hemostatic defect
28. Findings Disorders of
Platelet/1°
hemostatic defect
Disorders of
Coagulation/2°
hemosatic
defect
i) Petechiae
ii) Superficial
ecchymosis
iii) Deep dissecting
hematomas
iv) Haemarthrosis
v) Bleeding from the
superficial cuts &
scratches.
vi) Positive family
history
vii) Bleeding from
Characteristic
Characteristic,
usually small &
multiple
Rare
Rare
Persistent often
profuse
Rare
Prominent
Rare
Common, usually
large & solitary
Characteristic
Characteristic
Minimal
Common
May occur
29. Petechiae
( 1 – 2 mm )
Purpura
(≥ 3 mm)
Ecchymosi
s
(> 1 – 2
cms)
Petechiae: Tiny pin point ecchymoses
Purpura: Small reddish-purple discoloration on the skin that do not blanch on applyin
external presssure over them.
Ecchymosis: reddish or bluish discoloration on the skin due to extravasation of the blo
due to ruptured blood vessels. These patches are larger than pupura and do not blan
on applying external presssure over them
30. Screening Test for Primary Haemostasis
Hb,PCV-asses blood loss
Hess test
Bleeding time –platelet & vascular defects
Platelet count-Quantitation of platelets
PBS- 1) Quantitative & morphological
abnormalities of platelets 2)detection of
underlying hematological disorder
PFA-100 system-platelet function
31. Screening Test For Secondary
Haemostasis
CT- coagulation phase
PT-Extrinsic & common pathway
APTT-Intrinsic & common pathway
TT-Fibrinogen function
Editor's Notes
Platelet contain two types of cytoplasmic granules:
1. Alpha granules have ptns involved in coagulation: Fibrinogen, Factor V, Fibronectin, Platelet factor 4, PDGF, TGF-beta.
2. Dense or delta granules have ADP, ATP, Calcium ions, Serotonin, epinphrine.
The extrinsic pathway is activated by external trauma (tissue damge) that causes blood to escape from the vascular system. This pathway is quicker than the intrinsic pathway.
The intrinsic pathway is activated by trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen.
AAAAAWEEE468O;P[
Anticoagulant : Normal endothelium shields coagulation factors from tissue factor in vessel wall, also release thrombomodulin, endothelial protein C receptor, heparin-like molecules, and tissue factor pathway inhibitor. Thrombomodulin bind thrombin , by this thrombin loses its ability to activate coagulation factors and platelets, and instead cleaves and activates protein C, a vitamin K–dependent protease that requires a cofactor, protein S. Activated protein C/protein S complex is a potent inhibitor of coagulation cofactors Va and VIIIa. Heparin-like molecules on the surface of endothelium bind and activate antithrombin III, which then inhibits thrombin and factors IXa, Xa, XIa, and XIIa. Tissue factor pathway inhibitor (TFPI), binds and inhibits tissue factor/factor VIIa complexes.