Extrinsic Pathway of Coagulation

Summary

The extrinsic pathway of coagulation is one of 2 starting pathways used to form a stable blood clot. The extrinsic pathway starts when factor 7 circulating inside the blood is exposed to tissue factor from outside the blood, signifying an injury to the vessel. This reaction causes the cleavage and activation of factor 7, in a process that also requires calcium ions, phospholipids from a membrane, and vitamin K. The activated factor 7 then goes onto cleave factor 10, activating that protein to go onto cleave other things. The activation of factor 10 is the end of the extrinsic pathway and the beginning of the common pathway of coagulation. Importantly, we can use the PT or prothrombin time to monitor the status of the extrinsic pathway of coagulation.

Key Points

• Extrinsic Pathway of Coagulation
  • Also known as the tissue factor-mediated pathway
  • Pathway
    • Activation by cleavage of Factor VII → VIIa
      • Requires tissue factor, calcium (Ca2+), phospholipid
      • Vitamin K-dependent clotting factor
        • Inhibited by Warfarin
    • Factor VIIa + Tissue factor (as a cofactor) helps cleave Factor X → Xa
      • Factor Xa marks the end of the extrinsic pathway and the beginning of the common pathway
  • Monitoring
    • PT (prothrombin time)
      • PT measures time to clotting (extrinsic and common pathways) after tissue factor is added
      • PT is the best measure of warfarin effectiveness or vitamin K deficiency since factor VII has the shortest half-life among all vitamin K-dependent factors
      • Many commercial PT tests also include heparin inhibitors like polybrene (reinforcing its utility for warfarin monitoring over heparin)
      • Mnemonic: “play tennis outside” = PT measures extrinsic
    • INR (international normalized ratio)
      • INR is a normalized ratio of a patient’s PT over the international average (~1 is normal or average)