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Thread: The Clotting Cascades

  1. #1

    Default The Clotting Cascades

    The Clotting Cascades



    When tissue damage occurs, platelets become activated, aggregate, and adhere to the site of vascular injury where they form a thrombus. During this process, the blood coagulation cascade is initiated when the tissue factor comes in contact with factor VII (or factor VIIa [approximately 1% of total VII/VIIa in plasma]) in the flowing blood and forms:

    1.A potent enzyme complex at the site of injury. The complex of factor VIIa and TF catalyzes the conversion of factor X to factor Xa.

    2.Factor Xa converts prothrombin (II) to thrombin (IIa) in the presence of factor Va, phospholipid, and calcium (IV).

    3.Thrombin converts fibrinogen (I) to fibrin (Ia), leading to an insoluble clot of activated platelets and fibrin polymers.

    4.Thrombin activates XI to factor XIa (intrinsic pathway)

    5.Factor XIa converts factor IX to factor IXa in the presence of calcium.

    6.Factor IXa coverts factor X to factor Xa in the presence of factor VIIIa, phospholipid, and calcium.

    7.Thrombin converts factor V to Va.

    8.Thrombin converts factor VIII to VIIIa.

    9.Thrombin converts protein C to serine proteases.

    10.Thrombin converts XIII to a transglutaminase.

    11.Thrombin activates platelets.
    Last edited by admin; Fri 13th May '16 at 10:50pm.
    Clinical Pharmacy Specialist - Hematology

  2. #2
    Administrator admin's Avatar
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    Default Re: The Clotting Cascades

    The role of surfaces in coagulation and coagulation inhibition and fibrinolysis

    Functionally, the relationship between clotting and surface is striking. For a process that is typically termed humoral, most of the coagulation reactions take place on biologic surfaces.


    • The presence of a phospholipid surface increases the rate of activation of prothrombin by several orders of magnitude.
    • The presence of a phospholipid surface also localizes the reaction to the site of injury and may protect the reaction from inhibitors.
    • The activation of protein C by thrombin is a reaction that occurs on a cellular surface.
    • Coagulation inhibitors such as antithrombin and heparin cofactor II are also more efficient when the reactions occur on surfaces. The typical surface in these reactions is glycosaminoglycans like heparin, heparin sulfate, and derma tan sulfate.



    Factor VII

    Factor VII is highly homologous in its amino acid sequence and gene organization with the other vitamins K-dependent protein, including IX, X, and protein C. In the presence of TF, factor VII initiates the extrinsic pathway.

    Factor VII is converted to a serine protease by minor proteolysis, factor VIIa, which however has little if any physiologic activity until it combines with TF. The factor VIIa-TF complex then converts factor X to factor Xa in the presence of phospholipids and calcium ions.

    Factor VIIa also converts factor IX to factor IXa in the presence of TF and calcium ions. (physiological importance of which is unclear)

    Tissue Factor (TF)

    When blood comes into contact with the subendothelium following vascular injury, factor VII binds to TF to form a bimolecular complex in the presence of calcium ions, initiating coagulation.

    Factor X

    Factor V

    Prothrombin

    Factor XI

    Factor IX

    Factor VIII

    Fibrinogen

    Factor XIII

    Protein C

    Protein S

    Antithrombin III
    Last edited by admin; Fri 13th May '16 at 11:38pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease. Chengdu, Sichuan, China.

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  3. #3
    PharmD Year 1 TomHsiung's Avatar
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    Default Re: The Clotting Cascades

    aPTT assess intrinsic and common coagulation system including FI FII FV FVIII FIX FX FXI and FXII.

    PT assess extrinsic and common coagulation system including FI FII FV FVII and FX
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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