Hemostasis

Defination:

Prevention of blood loss.

Events Involved In Hemostasis

Whenever a vessel is ruptured, hemostasis is achieved by:

1. Vascular constriction

2. Formation of a platelet plug

3. Formation of a blood clot as a result

of blood coagulation.

4. Eventual growth of fibrous tissue into

the blood clot to close the hole in the

vessel permanently.

Vascular Constriction

• In ruptured blood vessel

1. Pain impulses from the site of trauma

reach the spinal cord.

• From the spinal cord order signal arise.

• through the sympathatic nerves

• Lead to spasm of the vessel.

2. Local muscle also contribute to the

vascular vasospasm.

3. local autacoid factors from the

traumatized tissues and blood

platelets.

• The vasospasm lasts for almost half an

hour and it is directly proportional to

the intensity of trauma.

In the smaller vessels, the platelets are

responsible for much of the

vasoconstriction by releasing a

vasoconstrictor substance,

thromboxane A2.

Formation of the Platelet Plug

Platelets

• Platelets or thrombocytes are small

colorless, non nucleated cells.

• Shape is spherical or rod shaped and

become oval or disc shaped when

inactivated.

• Size: 1 to 4 micrometers in diameter.

• Life span: 10 - days

• Development: From the pluripotentstem

cells in the bone marrow.

• CFU-M Colony forming megakaryocytes

• Megakaryoblast

• Promegakaryoctye

• Megakaryocytes

• Platelets

Normal concentration:

• 150,000 to 300,000 per microliter.

• Structure:

• Cell membrane

• Cytoplasm

Cell Membrane of Platelet

• It is 6 nm thick and contain lipids

(phospholipids, cholesterol and

glycolipids),Carbohydrates(glycocalyx),

Proteins and glycoproteins.

• Out of all glycoprotein and

phospholipids are functionally

important.

Glycopropteins

• Prevents the adherence of platelets to

normal endothelium.

• Accelerates the adherence of platelets

to collagen and damaged endothelium

in ruptured blood vessels.

• Forms a receptor for ADP and

thrombin.

Cytoplasm The cytoplasm of the platelets include:

• Golgi apparatus

• Endoplasmic reticulum

• Mitochondria

• Microtubule

• Microvessels

• Microfilaments

• Granules

Cytoplasm also contains:

• Proteins

• Enzymes

• Hormones.

• Chemical substances

Proteins

The major proteins present are

contractile proteins which are

responsible for the contraction of

platelets:

• Actin

• Myosin

• Thrombosthenin

Chemical substances:

• Calcium ions

• Mg- ions.

• Adenosine triphosphate (ATP)

• Adenosine diphosphate (ADP)

Function Of Platelets

• Its surface has glycoprotein coat that

adhere it to injured endothelial cells…

….preventing bleeding.

• Actin, myosin & thrombosthenin that

are contractile proteins…. cause clot

retraction.

• Secretes growth factor that promotes

growth & multiplication of vascular

endothelial cells, vascular smooth cells

& fibroblasts…. repair damaged

vascular wall.

• Its membrane has phospholipids that

activate intrinsic system of blood

clotting

Life span Of Platelets

• Platelets are eliminated from the

circulation mainly by the tissue

macrophage system in the spleen.

Mechanism of the Platelet Plug

• When platelets come in contact with a

damaged vascular surface, platelets

attach to the exposed collagen fibers in

the vascular wall.

• Platelets immediately change their own

characteristics.

• Platelets begin to swell and assume

irregular forms with numerous

irradiating pseudopods protruding from

their surfaces

• Contractile proteins in the platelets

contract forcefully and cause the

release of granules that contain

multiple active factors

• Adenosine diphosphate (ADP) is

released which causes surface of

nearby circulating platelets to become

sticky and it adheres to the first layer of

aggregated platelets

• The aggregated platelets adhere to the

von Willebrand factor that leaks into

the traumatized tissue from the plasma

• It leads to the release of more ADP ,

which cause more platelets to pile up at

the defected site.

• The aggregating process is reinforced

by the formation of Thromboxane A2.

• It directly promotes platelet

aggregation and further enhances it

indirectly by triggering the release of

even more ADP from the platelet

granules.

• Formation of platelet plug takes place

• Thirdly, the platelet plug release other

chemical substances that play a role in

blood clotting.

• Platelet plugging mechanism alone is

sufficient to seal tears in the capillaries

and small vessels but, large holes

require formation of blood clot to stop

bleeding.

Limitation of Platelet Plug

• Normal endothelium of the vessel

release Prostacyclin which prevents

platelet aggregation.

• So, platelet plug is limited to the

defected part of the vessel and does

not spread to the normal vascular

tissue.

Formation Of Blood Clot

• If there is a large defect in the vessel

then blood clot + platelet plug are

required to stop bleeding.

• A clot on the top of platelet plug

supports it and reinforces the seal over

the break in the vessel.

Onset Of Formation Of Blood Clot:

• 15 – 20 sec…… in severe trauma.

• 1 – 2 min…… in minor trauma.

• Ultimate step in clot formation is the

conversion of fibrinogen which is a

soluble protein that is produced by the

liver and is normally always present in the

plasma to fibrin which is insoluble thread

like molecule.

thrombin

Fibrinogen Fibrin

• Fibrin molecules adhere to the

damaged vessel surface forming a

loose netlike meshwork that traps the

cellular elements of blood.

• The clot appears red because of

abundance of RBC that are trapped in

it.

• The original fibrin web is weak

because the fibrin threads are loosely

interlaced.

• Rapidly, various chemical linkages are

formed between adjacent strands to

strengthen and stabilize the clot mesh

work.

• The cross linkage process which is

catalyzed by a clotting factor known as

factor XIII (Fibrin stabilizing factor).

Fibrous Organization or Dissolution of the Blood

Clot

Once a blood clot has formed, it can

follow one of two courses:

• It can become invaded by fibroblasts,

which subsequently form connective

tissue all through the clot.

• It can dissolve.

• The usual course for a clot that forms

in a small hole of a vessel wall…… is

invasion by fibroblasts, beginning

within a few hours after the clot is

formed.

• This event is promoted at least partially

by growth factor secreted by platelets.

• Complete organization of the clot into

fibrous tissue takes place within 1 to 2

weeks.

• When excess blood has leaked into the

tissues and tissue clots have occurred

where they are not needed.

• Special substances within the clot itself

usually become activated. These

function as enzymes to dissolve the

clot.

Mechanism of BloodCoagulation

Procoagulants:

• Substances that cause or affect blood

coagulation that have been found in

the blood and in the tissues…. promote

coagulation

Anticoagulants:

• Substances that inhibit coagulation are

called Anticoagulants.

• Whether blood will coagulate depends

on the balance between these two

groups of substances.

• In the blood stream, the anticoagulants

normally predominate, so that the

blood does not coagulate while it is

circulating in the blood vessels.

• But when a vessel is ruptured,

procoagulants from the area of tissue

damage become “activated” and

override the anticoagulants, and then a

clot does develop.

Three Essential Steps Involved In Clotting:

(1) In response to rupture of the vessel or

damage to the blood itself, a complex

cascade of chemical reactions occurs

in the blood involving more than a

dozen blood coagulation factors.

• Formation of a complex of activated

substances collectively called

prothrombin activator.

(2) The prothrombin activator catalyzes

conversion of prothrombin into

thrombin in the presence of

sufficient amounts of ionic Ca++.

(3) The thrombin acts as an enzyme to

convert fibrinogen into fibrin fibers that

mesh with platelets, blood cells, and

plasma to form the clot.

• The clotting cascade may be triggered

by the intrinsic pathway or the extrinsic

pathway:

• The intrinsic pathway precipitates

clotting within damaged vessels as well

as clotting of blood samples in test

tubes.

• All elements necessary to bring about clotting by means of the intrinsic pathway are present in the blood.

Extrinsic pathway for initiating clotting