Blood coagulation pathway with extrinsic and intrinsic mechanism

1. PHARM.D. Dr G. S. Damre
HEMOSTASIS/ BLOOD COAGULATION
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel,
forming a blood clot
When blood vessels are damaged or ruptured, the hemostatic 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) platelet plug formation
(3) blood clotting (coagulation)
Vascular Spasm :
When arteries or arterioles are damaged, the circularly arranged smooth muscle in
their walls contracts immediately, a reaction called vascular spasm. This reduces blood
loss for several minutes to several hours, during which time the other hemostatic mechanisms
go into operation. The spasm is probably caused by damage to the smooth muscle, by
substances released from activated platelets.
Platelet plug formation :
 Platelet adhesion
 Platelet release reaction
 Platelet aggregation
1.initially, platelets contact and stick to parts of a damaged blood vessel and endothelial .
This process is called platelet adhesion.
2 Due to adhesion, the platelets become activated, and their charaacteristics change
dramatically. They extend many projections that enable them to contact and interact with one
another, and they begin to liberate the contents of their vesicles. This phase is called the
platelet release reaction. Liberated ADP and thromboxane A2 play a major role by
activating nearby platelets.
3.The release of TXA2 and ADP makes other platelets in the area sticky, and the
stickiness of the newly recruited and activated platelets causes them to adhere to the

2. PHARM.D. Dr G. S. Damre
originally activated platelets. This gathering of platelets is called platelet aggregation.
Eventually, the accumulation and attachment of large numbers of platelets form a mass
called a platelet plug.
Blood coagulation :
Clotting involves several substances known as clotting (coagulation) factors. These factors
include calcium ions (Ca2), several inactive enzymes that are synthesized by hepatocytes
(liver cells) and released into the bloodstream
Clotting involves several substances known as clotting (coagulation) factors. These factors
include calcium ions (Ca2), several inactive enzymes that are synthesized by hepatocytes
(liver cells) and released into the bloodstream
Extrinsic Pathway
Tissue factor I.e. thromboplastin released by damaged tissue .
thromboplastin leaks into the blood from cells outside (extrinsic to) blood vessels and
initiates the formation of prothrombinase. TF is a complex mixture of lipoproteins and
phospholipids released from the surfaces of damaged cells. In the presence of Ca2, TF begins
a sequence of reactions that ultimately activates clotting factor X. Once factor X is activated,
it combines with factor V in the presence of Ca2 to form the active enzyme prothrombinase,
completing the extrinsic pathway
Intrinsic Pathway :
If endothelial cells become roughened or damaged, blood can come in contact with collagen
fibers in the connective tissue around the endothelium of the blood vessel. In addition, trauma
to endothelial cells causes damage to platelets, resulting in the release of phospholipids by the
platelets. activates clotting factor XII , which begins a sequence of reactions that eventually
activates clotting factor X. Platelet phospholipids and Ca2 can also participate in the
activation of factor X. Once factor X is activated, it combines with factor V to form the
active enzyme prothrombinase (just as occurs in the extrinsic pathway), completing the
intrinsic pathway
Common Pathway:
The formation of prothrombinase marks the beginning of the common pathway. In the second
stage of blood clotting . prothrombinase and Ca2 catalyze the conversion of prothrombin to

3. PHARM.D. Dr G. S. Damre
thrombin. In the third stage, thrombin, in the presence of Ca2, converts fibrinogen, which is soluble,
to loose fibrin threads, which are insoluble. Thrombin also activates factor XIII (fibrin stabilizing
factor), which strengthens and stabilizes the fibrin threads into a sturdy clot.