II. Images

  1. Overview
    1. pathClottingCascade.png
  2. Full Thrombosis Pathway
    1. ThrombosisPathway.png

III. Physiology: Pathway

  1. Antagonized by Clotting Pathway Inhibition
  2. Common Clotting Pathway is triggered by two different initiating pathways
    1. Intrinsic Clotting Pathway
      1. Initiated by Negatively charged surface of foreign material or from damaged Red Blood Cells
      2. Pathway is relatively slow (minutes to form blood clot)
        1. Factor XII to Factor XI to Factor IX and Factor VIII which trigger conversion of Factor X to Xa
        2. Factor Xa then proceeds into the common pathway, generating Thrombin and then Fibrin
    2. Extrinsic Clotting Pathway
      1. Initiated by disrupted cell membranes
      2. Damaged cells (including vascular endothelial cells) release Tissue Thromboplastin
      3. Pathway is relatively rapid with Blood Clotting occuring within 15 seconds
        1. Factor VII, Factor V and Calcium combine to trigger conversion of Factor X to Xa
        2. Factor Xa then proceeds into the common pathway, generating Thrombin and then Fibrin
  3. Common Clotting Pathway
    1. Factor Xa
      1. Cofactor: Factor V
      2. Inhibitors
        1. Protein C
        2. Protein S
        3. Medications: Direct Xa Inhibitors
    2. Factor II (Prothrombin) converted to IIa (Thrombin)
      1. Fibrinogen cleaved (catalyzed by Thrombin)
        1. Fibrinogen cleaved to Fibrin Monomer
        2. Fibrin Monomer coalesced into Fibrin Polymer
      2. Fibrin combines with Platelets, plasma factors and Red Blood Cells to form blood clot
      3. Factor XIII converted to XIIIa
        1. Fibrin polymer cross-linked

IV. Causes: Abnormal Common Clotting Pathway

  1. Severe liver disease
    1. Liver synthesizes Prothrombin, Fibrinogen and other Clotting Factors
  2. Vitamin K Deficiency
    1. Clotting Factors (both pro-coagulant and Anticoagulant, including Prothrombin) are Vitamin K Dependent
  3. Medications
    1. Warfarin
    2. Heparin

V. Labs: Prolonged Times in Common Clotting Pathway Disorders

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