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Coagulation Pathways

- See:
     - deep venous thrombosis
     - hypercoagulable states 

                XII + Surface: intrinsic path: heparin/ PT
                  |            VIIa + TF: extrinsic path: (warfarin/PT)
                XI---XIa <----/    
                   VIIIa |      
                         |                                Thrombomodulin
                      X----------Xa                --------> Prot. C/S --
                     /           | Va                                 |
                    /            |                                    |
     Antithrombin III ----->  II-------IIa ----------------------> VIIIa & Va

- Specific Factors:
    - fibrinogen (factor I);
    - prothrombin (factor II)
           - converts finbrinogen to fibrin
           - activates V, VIII & XIII (when bound to thrombomodulin)
           - activates protein C;
           - Vit K dependent;
    - factor V: 
           - when activated, serves as enzyme co-factor;
           - mutation leads to Leiden thrombophilia (decreased inactivation of factor V and thus a greater tendency to form clots)
           - ref: Factor V Leiden Thrombophilia 
    - factor Xa: part of Xa/Va complex which activates prothrombin;
    - factor VII:
           - part of factor VII/tissue factor complex that activates factor X and IX;
           - is activated by Xa;
           - Vit K dependent;
    - factor VIII: serves as enzyme cofactor to help activate factor X; 
           - deficiency of this factor leads to hemophilia
    - factor IX:
           - acts w/ IXa/VIIIa/phos complex that activates factor X;
           - Vit K dependent;
    - factor X:
           - acts as Xa/Va phos complex that actives prothrombin; 
           - this factor is inhibited by lovenox and other low molecular wt heparins;
           - Vit K dependent; 
           - see lovenox and rivaroxaban
           - ref: The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulants.
    - factor XII:
    - protein C:
           - when activated to Ca by thrombin bound to thrombomodulin, inhibits by proteolysis factors VIIIa and Va in reactions
                  requiring prot S and phospholipids as cofactors; Vit K dependent;
    - antithrombin III:
           - is a plasma protease inhibitor that serves as a protease scavenger;
           - any of the blood-clotting enzymes that move away from the growing clot rapidly form a complex, and their activities are
           - formation of complexes is accelerated by heparin, forms of which are located in the microvasculature on the surfaces of
                       endothelial cells;
           - inhibitor of the enzymes thrombin, Xa, IXa; Is activated by  heparin 
           - see arixtra

Medical Progress: The regulation of hemostasis: the protein C system.

Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis.

Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40.

The effect of total hip replacement and general surgery on antithrombin III in relation to venous thrombosis.

Coffee consumption is associated with a reduced risk of venous thrombosis that is mediated through hemostatic factor levels

Review Article: Seminars in Medicine of the Beth Israel Hospital, Boston: Molecular and cellular biology of blood coagulation.

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