RGS College of Pharmacy, Anjaneri, Nashik

Topic: Blood Clotting (HAP) Prepared by, Mr. Bachhav R.S.

Hemostasis is a sequence of response that stops bleeding. When blood vessels are
damaged or ruptured, the haemostatic response must be quick, localized to the region of
damage and carefully controlled in order to be effective.
Three mechanisms reduce blood loss;
1) Vascular spasm.
2) Platelets plug formation.
3) Blood clotting.
1) Vascular spasm:
When arteries and arterioles are damaged, the circularly arranged smooth muscle in
their walls contract immediately, a region called vascular spasm.
2) Platelets plug formation:
Platelets store an important chemicals like clotting factor, ADP, ATP, Calcium and
serotonin the enzyme which produce thromboxane A2, a prostaglandin; fibrin
stabilizing factor. Also within platelets is platelet –derived growth factor, a hormone
that cause proliferation of vascular endothelial cells, vascular smooth muscle fibers,
and fibroblast to help repair damaged blood vessel wall.
Platelets plug is very effective in preventing blood loss in small vessel. The
accumulation and attachment of large number of platelets form a mass called platelet
plug.
3) Blood clotting:
Normally blood remains in its liquid form as long as it stays within its vessels. If it is
drawn from the body, however, its thickens and forms a gel. Eventually gel separate
from liquid .The straw colored liquid called serum.
Serum =blood plasma-clotting protein.
The process of formation of gel formation called clotting or coagulation, is a series of
chemical reaction that culminate in formation of fibrin threads.
The blood clots too easily, the result can be thrombosis - clotting in an undamaged
blood vessel. If blood takes too long too clot, hemorrhage can occur.
 Clotting involves several substances known as clotting factor or coagulation factor.
Clotting factor includes calcium ions, and several inactive enzymes that are
synthesized by hepatocytes and released into blood stream and various molecules
associated with platelets or released by damaged tissues.
Clotting is complex cascade of enzymatic reaction in which each clotting factor
activates many molecule of the next one in a fixed sequence. Finally large quantity of
product is formed.
Clotting can be divided into three pathways.
1) Two pathways, called extrinsic pathway and intrinsic pathway, which will lead
to formation of prothrombinase. Once prothrombinase is formed, the steps
involved in the next two stage of clotting are the same for both the extrinsic and
intrinsic pathway, a together these two stages are referred to as common
pathway.
2) Prothrombinase converts prothrombin (a plasma protein formed by liver) into
the enzyme thrombin.
3) Thrombin converts soluble fibrinogen into fibrin (insoluble). Fibrin forms a
thread of the clot.

1) The Extrinsic pathway:

1) It has fewer steps than intrinsic pathway.
2) It occurs rapidly within matter of second, if trauma is sever.
3) It is so named because a tissue protein called tissue factor (TF), also known as
thromboplastin, leaks into to the blood from cell outside (extrinsic) to blood
vessel and initiate formation of prothrombinase.
4) Tissue factor is a complex mixture of lipoprotein and phospholipids.
5) In the presence of calcium, TF begins a sequence of reaction that ultimately
activates clotting factor X.
6) Once Factor X is activated, it combines with factor V in the presence of calcium
to form active enzyme prothrombinase completing the extrinsic pathway.
 2) The Intrinsic pathways:
1) It is more complex pathway than extrinsic pathway.
2) It occurs more slowly usually requiring several minutes.
3) The intrinsic pathway so named because its activators are either in direct contact
with blood or contained within blood.
4) Outside tissue damage is not needed.
5) If endothelial cell roughened or damaged, blood can come in contact with
collagen fibers in the connective tissue around the endothelium of blood vessel.
6) Trauma to endothelial cell cause damaged to platelets resulting in the release of
phospholipids by platelets.
7) Contact with collagen fiber activate clotting factor XII, which begins a sequence
of reaction that eventually activate clotting factor X.
8) Platelets phospholipids and calcium can also participate in the activation of factor
X.
9) Once factor X is activated, it combines with factor V to form active enzyme
prothrombinase.

3) The common pathway:

1) Prothrombinase is starter for common pathway.
2) Prothrombinase and calcium catalyses the conversion of prothrombin to thrombin.
3) Thrombin in the presence of calcium converts fibrinogen , which is soluble , to
loose fibrin threads, which are insoluble.
4) Thrombin also activates factor XIII , which strengthens and stabilizes the fibrin
threads into sturdy clot.