Clotting Factors - Coagulation Cascade

GET LECTURE HANDOUTS and other DOWNLOADABLE CONTENT FROM THIS VIDEO

SUPPORT US ON PATREON OR JOIN HERE ON YOUTUBE.
https://www.patreon.com/medsimplified
There are 13 blood clotting proteins (coagulation factor) found in the blood. They are designated by Roman Numerals I through XIII. When a blood vessel is damaged, these clotting factors are switched on in a certain order (Blood Clotting Cascade) [link to coagulation page] and work to form a clot. Specifically, these 13 factors normally combine to a clot.

If one factor is missing or present at low levels, this causes hemophilia and other blood clotting problems and a proper clot will not form.

The two most common factor deficiencies are: factor 8 (or factor VIII) deficiency and factor 9 (or factor IX) deficiency. The most common, affecting 80% of the hemophilia population - those with hemophilia A - is factor VIII. When these blood clotting proteins aren't present is not easily stopped.

This factor is so important to the treatment of hemophilia, that instead of saying they have "hemophilia A or B," most people say they are "Factor VIII" or "Factor IX" to identify their condition.

Various substances are required for the proper functioning of the coagulation cascade:

Calcium and phospholipid (a platelet membrane constituent) are required for the tenase and prothrombinase complexes to function. Calcium mediates the binding of the complexes via the terminal gamma-carboxy residues on FXa and FIXa to the phospholipid surfaces expressed by platelets, as well as procoagulant microparticles or microvesicles shed from them. Calcium is also required at other points in the coagulation cascade.
Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase that adds a carboxyl group to glutamic acid residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z. In adding the gamma-carboxyl group to glutamate residues on the immature clotting factors Vitamin K is itself oxidized. Another enzyme, Vitamin K epoxide reductase, (VKORC) reduces vitamin K back to its active form. Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs warfarin and related coumarins such as acenocoumarol, phenprocoumon, and dicumarol. These drugs create a deficiency of reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors. Vitamin K deficiency from other causes (e.g., in malabsorption) or impaired vitamin K metabolism in disease (e.g., in liver failure) lead to the formation of PIVKAs (proteins formed in vitamin K absence) which are partially or totally non-gamma carboxylated, affecting the coagulation factors' ability to bind to phospholipid.

Tissue factor pathway (extrinsic)[edit]
The main role of the tissue factor pathway is to generate a "thrombin burst", a process by which thrombin, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released very rapidly. FVIIa circulates in a higher amount than any other activated coagulation factor. The process includes the following steps:[7]

Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF) expressed on tissue-factor-bearing cells (stromal fibroblasts and leukocytes), forming an activated complex (TF-FVIIa).
TF-FVIIa activates FIX and FX.
FVII is itself activated by thrombin, FXIa, FXII and FXa.
The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI).
FXa and its co-factor FVa form the prothrombinase complex, which activates prothrombin to thrombin.
Thrombin then activates other components of the coagulation cascade, including FV and FVIII (which activates FXI, which, in turn, activates FIX), and activates and releases FVIII from being bound
wATCH AGAIN
https://www.youtube.com/watch?v=R1wYycfGFjU
SUBSCRIBE
https://www.youtube.com/channel/UCOmrniWfKi-uCD6Oh6fqhgw

-~-~~-~~~-~~-~-
CHECK OUT NEWEST VIDEO: "Nucleic acids - DNA and RNA structure "
https://www.youtube.com/watch?v=0lZRAShqft0
-~-~~-~~~-~~-~-

Видео Clotting Factors - Coagulation Cascade канала MEDSimplified