1. BLEEDING AND
COAGULATION
DISORDERS
Dr. Shamshuddin Patel Sr.

2. HEMOSTASIS
• Def. : consequence of tightly regulated
processes that maintain blood in a fluid,
clot-free state in normal vessels while
introducing the rapid formation of a
localized haemostatic plug at the site of
vascular injury.
- from Robbins Basic Pathology 8th edition
• Mechanism
 vasoconstriction
 formation of platelet plug
 coagulation cascade
 fibrinolysis

3. WHY BLOOD DOES NOT CLOT NORMALLY
IN CIRCULATION?
• ENDOTHELIAL FACTORS:
– smoothness of endothelial lining prevents platelet
adhesion
– negatively charged particles present over endothelial lining
repel the clotting factors
• VELOCITY OF CIRCULATION, if decreases leads to
clotting
• PRESENCE OF NATURAL ANTICOAGULANTS IN BLOOD,
Ex: heparin, protein c, thrombomodulin
• SIMULTANEOUS ACTIVATION OF FIBRINOLYTIC
SYSTEM ALONG WITH CLOTTING MECHANISM.

4. Stages
of Hemostasis

5. 5
Vascular Spasm
Vascular spasm results from the:
1. Local myogenic contraction of the blood vessels initiated
by direct damage to the vascular wall
2. Release of Local autacoid factors from the traumatized
tissues and blood platelets, and
3. Nervous reflexes initiated by pain nerve impulses or
other sensory impulses that originate from the
traumatized vessel or nearby tissues.
4. Release of a vasoconstrictor substance, Thromboxane A2
by the platelets which for the smaller vessels are
responsible for much of the vasoconstriction

6. Mechanism of the Platelet Plug
• When platelets come in contact with a damaged vascular
surface, especially with collagen fibers in the vascular wall,
the platelets themselves immediately change their own
characteristics drastically
• They begin to swell
• They assume irregular forms with numerous irradiating
pseudopods protruding from their surfaces;
• Their contractile proteins contract forcefully and cause the
release of granules that contain multiple active factors
• They become sticky so that they adhere to collagen in the
tissues and to a protein called von Willebrand factor

7. Platelet plug formation: platelet adhesion

8. Mechanism of the Platelet Plug Formation
• They secrete large quantities of ADP and their enzymes
form Thromboxane A2
• The ADP and thromboxane in turn act on nearby platelets
to activate them as well, and
• The stickiness of these additional platelets causes them
to adhere to the original activated platelets
• Thus the damaged vascular wall activates successively
increasing numbers of platelets that themselves attract
more and more additional platelets, thus forming a
platelet plug

9. Platelet plug formation: platelet release
action

10. Platelet plug formation: platelet aggregation

11. THE PLATELET ROLE IN
HEMOSTASIS

12. COAGULATION
• Formation of blood clot
Stages of clotting
 Phase 1: Extrinsic and intrinsic pathways
produce prothrombinase/prothrombin
activator
 Phase 2: Prothrombinase converts
prothrombin to thrombin
 Phase 3: Thrombin converts soluble fibrinogen
into insoluble fibrin which is the thread of the
clot.

13. Clotting factors
in blood

14. Intrinsic Pathway
1. Blood trauma causes (a) activation of
Factor XII and (b) release of platelet
phospholipids (containing platelet
factor 3)
2. Activated Factor XII (XIIa)
enzymatically activates Factor XI
(XIa) which needs kininogen and is
accelerated by prekallikrein
3. Factor XIa enzymatically activates
Factor IX to IXa
4. Factor IXa+Factor VIIIa+platelet
phospholipids and factor 3 activates
Factor X to Xa
5. Factor Xa+Factor V+ platelet or
tissue phospholipid form the complex
called prothrombin activator
6. The prothrombin activator in turn
initiates within seconds the cleavage
of prothrombin to form thrombin

15. Extrinsic Pathway
1. Release of tissue factor:
Traumatized tissue releases a
complex of several factors called
tissue factor or tissue
thromboplastin
2. Activation of Factor X: Tissue
factor further complexes with
Factor VII and, in the presence of
calcium ions, acts enzymatically
on Factor X to form activated
Factor X
• Factor Xa forms prothrombin
activator— Factor Xa combines
with tissue or platelet
phospholipids as well as with
Factor V to form the complex
called prothrombin activator

16. Stage 1 Intrinsic Pathway Extrinsic Pathway
Endothelial damage + Collagen exposure
Kallikrein
HMW Kinogen
XII XIIa
HMW Kinogen
XI XIa
Calcium
IX IXa
Phospholipid
VIII &
Calcium
X Xa
Platelets
Tissue trauma + Tissue thromboplastin
(Glycoprotein+Phospholipiod)
Calcium
V
Prothrombin
Thrombin
Positive
feedback
Positive
Stage 2 feedback
Stage 3
Fibrinogen a Fibrinogen
Polymerization
Loose strands of Fibrin
VII
17-Oct-14 16
XIII & Calcium
Fibrin tight blood clot
Prothrombin activator
Xa X

17. HOW DOES BLOOD CLOT SUMMARY