BLEEDING AND

COAGULATION DISORDERS
Dr. Shamshuddin Patel Sr.

HEMOSTASIS
Def. : consequence of tightly regulated
processes that maintain blood in a fluid, clotfree state in normal vessels while
introducing the rapid formation of a
localized haemostatic plug at the site of
vascular injury.
Mechanism

- from Robbins Basic Pathology 8th edition

vasoconstriction
formation of platelet plug
coagulation cascade
fibrinolysis

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.

Stages
of
Hemostasis

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
5

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

Platelet plug formation: platelet

adhesion

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

Platelet plug formation: platelet

release action

Platelet plug formation: platelet

aggregation

THE PLATELET ROLE IN

HEMOSTASIS

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.

Clotting
factors in
blood

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

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

Intrinsic
Pathway
Endothelial
damage + Collagen

Extrinsic
Pathway
Tissue trauma
+ Tissue

Stage 1

(Glycoprotein+Phospholipi
thromboplastin

exposure
Kallikrein

od)

HMW Kinogen

XII

Platele
ts

XII
a

VII

HMW Kinogen

XI

XIa
Calcium

IX

IXa

Phospholipi
d

VIII &
Calcium

Xa

Calcium
V

Xa

Prothrombinactivator
activator
Prothrombin
Stage 2

Positive
feedbac
k

Prothromb
in

Polymerization

Stage 3
1/17/16

Thrombi
n
Fibrinogen
a

Loose strands of
Fibrin
XIII & Calcium

Positive
feedbac
k
Fibrinogen

Fibrin tight blood clot

16

HOW DOES BLOOD CLOT SUMMARY