Physiology : Hematology

Medicine . L3

PSL222.

Platelets &
Hemostasis.

Lecture No. 7
Dr S.Bashir

Objectives

Describe platelets synthesis, structure&

function.
Define hemostasis.
Describe the stages of hemostasis.
Explain why blood doesnt clot in normal
vessels.
Name common coagulopathies.
Describe the main approaches to mange
coagulopathies.
Dr S.Bashir

Platelets:
(thrombocytes)

Flattened, disk-like cell

fragments .
Essential for hemostasis.
Each platelet circulates for
9-12 days
Removed by splenic
macrophages.
There are 350,000/ uL of
blood.
Dr S.Bashir

Synthesis

Produced in the bone marrow.

Large cells called megakaryocytes release
fragments (platelets) into the circulation.
Dr S.Bashir

Platelet function:
platelet plug

Dr S.Bashir

Hemostasis

Definition?
There are several phases to hemostasis:

1. Vascular Phase

2. Platelet plug Phase

3. Coagulation Phase.

4. Fibrinolysis and resolution.

Dr S.Bashir

Vascular Phase-1

The smooth muscle cells in the

blood vessel wall respond to
damage. They CONTRACT. The
blood vessel diameter decreases
reduction in blood loss.
The reflex is immediate but
transient.
Injury expose the rough & sticky
collagen fibers in the basement
membrane of vessels( Extra Cell.
Matrix).
Dr S.Bashir

Platelet plug phase-2

Dr S.Bashir

Platelet Phase

Platelets attach to the

sticky & rough surface
in presence of Von
Willebrand factor.
Platelets activate
release chemicals
(thromboxane A2) that
attract and activate
more platelets a mass
of platelets temporarily
plugs the damage..
Dr S.Bashir

3-Coagulation Phase
A sequence of chemical
reactions conversion of
fibrinogen (a soluble circulating
plasma protein) into a meshwork
of the insoluble protein fibrin.
The fibrin meshwork grows
& cover the surface of the platelet
plug. RBC & more platelets are
trapped forming a blood clot.

Dr S.Bashir

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Mechanism of Coagulation

Phase

Injured tissues release thromboplastin,PF3

(a phospholipid)

PF3 interacts with blood protein clotting factors,

and calcium ions to trigger a clotting cascade.

Clotting factors are proenzymes (inactive

enzymes) that have to be converted to active
enzymes.
Dr S.Bashir

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Mechanism of Coagulation

Phase

During the coagulation

phase enzymes and
proenzymes interact.
The activation of one
proenzyme creates an
active enzyme that activates
another proenzyme that will
then activate a third and so
on yielding a chain reaction
or cascade.
Dr S.Bashir

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Mechanisms of Coagulation

Phase

Coagulation can be activated by either

Intrinsic pathway
Extrinsic pathway

The intrinsic pathway: all factors found

in blood.
The extrinsic pathway: requires tissue
factors resulting from tissue injury.
Dr S.Bashir

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THE CLOTTING MECHANISM

INTRINSIC

EXTRINSIC
Tissue Thromboplastin

Collagen
XII
XI
IX
VIII

VII

X
V
PROTHROMBIN
)II(

THROMBIN
)III(

FIBRINOGEN
)I (
FIBRIN

THE CLOTTING MECHANISM

EXTRINSIC
Tissue Thromboplastin
VII

X
V
PROTHROMBIN
)II(

THROMBIN
)III(

FIBRINOGEN
)I (
FIBRIN

Extrinsic Pathway
TF
Prothrombin
VIIa
Xa
Va

Thrombin
Fibrinogen

Fibrin

Intrinsic pathway
XIIa
Extrinsic Pathway
XIa
Prothrombin
IXa
VIIIa

Xa
Va

Thrombin
Fibrinogen

Fibrin

Intrinsic pathway

XIIa
Extrinsic Pathway
XIa
TF
Prothrombin
IXa
VIIIa

Fibrinogen

VIIa
Xa
Va

Thrombin

Soft clot
Fibrin
XIIIa

Hard clot
Fibrin

Extrinsic Pathway

Begins with the release of tissue

factor by damaged endothelial cells
or peripheral tissues.
The greater the damage the more
tissue factor released and the faster
clotting will occur.
In a few short steps, a chemical
called prothrombin activator ( F X)
will have been formed. Because
only a few steps are required, the
extrinsic path forms prothrombin
activator quickly.

Dr S.Bashir

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Intrinsic Pathway

Begins with the exposure of

collagen which starts the
activation cascade of several
proenzymes eventually
resulting in the production of
prothrombin activator ( FX).

Because there are several

steps, the intrinsic path does
not make (FX) as fast as the
extrinsic path. However,
multiple steps allows for more
amplification which means
more (FX) will be made more
fibrin

Dr S.Bashir

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Clot retraction-4

Dr S.Bashir

Platelets actin and

myosin fibrils, contract
clot retraction.
Firm & stable clot.
This also reduces the
size of the injured area,
making it easier for
fibroblasts, smooth
muscle cells, and
endothelial cells to
complete repairs.
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5-Fibrinolysis

As repairs proceeds, the clot gradually dissolves. This

dissolution is known as fibrinolysis.
Fibrinolysis begins with the activation of the proenzyme
plasminogen into plasmin
Plasmin digests the fibrin strands and erodes the
foundation of the clot.

Dr S.Bashir

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Hemostasis : summary

Dr S.Bashir

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Why doesnt blood clot in normal

vessels?

1-The normal
endothelium:
intact &
.
Endogenous
Inhibitors
of smooth
Hemostasis
2-Flow of blood. Stasis clotting tendency ?
3-Endothelium also secretes products which
inhibit platelet aggregation: nitric oxide and
prostacyclin. (antagonists for thromboxane A2)
4-Antithrombin (AT) (also called antithrombin
III , from the liver, inhibits thrombin (factor
IIa) .
5-Heparin from mast cells enhances AT.
Dr S.Bashir

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Why doesnt blood clot in

?normal vessels

Dr S.Bashir

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Bleeding Disorders & Coagulopathy

Dr S.Bashir

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Bleeding Disorders & Coagulopathies

(practical)

Platelet disorders .
Blood vessel wall disorders .

Congenital Coagulopathies:
Hemophilia A : def. of F VIII
Hemophilia B : def. of F IX
Von Willibrands Diseases.

Acquired Coagulopathies: Vitamin K Deficiency .

Liver Diseases.

Dr S.Bashir

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:Vitamin K def

Synthesized by bacterial flora in large

intestine.
Stimulates liver synthesis of factors II, V,
VII , X.
Deficiency in:
Newborns, specially premature ones.
Why?
Prolonged use of antibiotics. Why?
Dr S.Bashir

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Abnormal Clotting in intact vessels

Thrombosis .
Embolism.
Disseminated
intravascular
coagulation

Dr S.Bashir

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Thrombus

A thrombus is formed
when platelets stick to
the wall of an intact
blood vessel.

This occurs in areas

where endothelial cells
of vessel walls contain
lots of lipids plaques.
Dr S.Bashir

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Thrombus

A large thrombus may

block a vein

Deep Vein Thrombosis

Blood stasis increase risk of

DVT.
Causes of stasis?
Immobilization after
fractures/ surgery,
delivery, Long flights.
Dr S.Bashir

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Exercise during flying,

?why

Dr S.Bashir

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Embolus

If the thrombus breaks

off & travels in the
bloodstream, it's called
an embolus.
Embolus blocks an
artery

Brain stroke.
Pulmonary embolism.
Myocardial infarction
Dr S.Bashir

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Treatment of coagulopathies

Dr S.Bashir

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Exogenous anti-coagulants

Heparin, which works by inactivating thrombin.

Cannt be taken orally & has to be injected.

Coumadin ,warfarin, which prevents the liver

from utilizing vitamin K (necessary for the
production of clotting factors). Taken orally.

Aspirin, which inhibits platelet aggregation and

prostaglandins synthesis (Thromboxane A2 but
also prostacycline.)
Dr S.Bashir

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Thrombolytic agents

Given to patients who develop thrmbosis

blocking vessels.
Streptokinase: from streptococcal bacteria.
Urokinase : from urine.
t-PA (tissue plasminogen activator):
synthetic ( genetic engineering), should be
administered as early as possible
( with
in 3 hrs).
Dr S.Bashir

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:Prevention of clotting in the lab

Heparinized containers.

Add Ca ++ chelating agents : EDTA,

citrates .

Dr S.Bashir

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?How to stop external bleeding

Dr S.Bashir

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Thank You

Dr S.Bashir

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