3. Clotting Cascade
Finalizes in fibrin clot formation
2 pathways:
1)Intrinsic
2)Extrinsic pathway
Both pathways finalize in Factor 10a formation
Both pathways involve a common pathway of
prothrombin to thrombin formation.
4. Factor 3 and 7 deals specifically with Extrinsic
pathway activation of Factor 10 to 10a and
prothrombin to thrombin.
This leads to fibrin clot formation.
5. Factor 3: Tissue Factor
(CD1420 cluster of
differentiation)
Cell surface glycoprotein
Subendothelial tissue protein and on leukocytes
Tissue factor is found on the outside of blood vessels - normally not exposed to
the bloodstream.
Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII.
Necessary for initiation of thrombin formation from zymogen prothrombin
Unique from other 13 factors in blood, factor 3 is a potent initiator that is fully
functional when expressed on cell surfaces
High-affinity receptor for the coagulation factor VIIa
3 distinct domains of this factor: extracellular, transmembrane, and cytoplasmic
This protein is the only one in the coagulation pathway for which a congenital
deficiency has not been described (deadly)
6.
7. Factor 7
Serine protease enzyme.
Initiates coagulation process with Factor 3 (Tissue
Factor).
Upon vessel injury, tissue factor is exposed to the
blood and circulating Factor 7.
Once bound to Factor 3, Factor 7 is activated to
Factor 7a
Factor 7 is vitamin K dependent and produced in
the liver. Use of warfarin or similar anticoagulants
decreases hepatic synthesis of FVII.
Pathology: Factor 7 deficiency presents as a
hemophilia-like bleeding disorder.
Treatments: recombinant Factor 7a for uncontrolled
bleeding in hemophelia.
8.
9. Factor 3 and 7 together deal specifically with
Extrinsic pathway activation of Factor 10 to 10a
and prothrombin to thrombin resulting finally in
fibrin clot formation.
10.
11. REFERENCES
Bajzar L, Morser J, Nesheim M (July 1996). TAFI, or
plasma procarboxypeptidase B, couples the
coagulation and fibrinolytic cascades through
the thrombin-thrombomodulin complex. J. Biol.
Chem. 271 (28): 16603–8.
Jakubowski HV, Owen WG (July 1989).
Macromolecular specificity determinants on
thrombin for fibrinogen and thrombomodulin. J.
Biol. Chem. 264 (19): 11117–21.
Van den Besselaar AM, Chantarangkul V, Tripodi
A (July 2010). "Thromboplastin standards".
Biologicals 38 (4): 430–6.