SECONDARY

• The platelet plug formed in primary hemostasis is unstable/reversible and needs to be stabilized using clotting factors
• Speaker: 'Quote'
• Clotting factors circulate in the plasma mostly inactive, except for III and IV which are active, especially IV (calcium). Factor III, once released by tissues, automatically activates other factors
• Cofactors speed up enzymatic activities
• Hemostasis, particularly coagulation, is compared to a waterfall effect or a domino effect where one activation leads to another until reaching the end point
• For a product to be formed, a substrate is needed
• Clotting factors

  • Fibrinogen
  • Prothrombin
  • Tissue Factor
  • Calcium
  • Pro-accelerin
  • Proconvertin
  • Stuart factor
  • Antihemophilic factor A
  • Plasminogen
  • Complement component C1
  • etc...
• Factor VII circulates in the plasma inactively and requires another clotting factor, particularly factor III, for activation
• The secondary hemostatic process involves enzymatic activities, particularly serine proteases, with clotting factors generally being enzymes, specifically serine proteases
• Secondary hemostasis involves the activation of a series of coagulation proteins in the plasma to form a fibrin clot
• Secondary hemostasis refers to the interaction of all coagulation proteins, involving all the proteins in the plasma that can form a clot, known as clotting factors
• Factor XII is attracted to the negative charge of exposed collagen and gets cleaved or activated
• Clotting factors are proteins acting as enzymes, known as zymogens, synthesized by the liver except for III and IV which are in the tissues
• Primary hemostasis

  Formation of a platelet plug/aggregate (white clot)
• Inhibiting coagulation proteins and clotting factors

  Through regulatory proteins, control proteins, inhibitors
• Enzyme types

  • Serine protease, transaminase
• Factor XIII helps stabilize clot that was formed before
• Prothrombin group


  Vitamin K dependent group involved in metabolic activities of amino acids of these proteins
• Clotting factors involved in each pathway

  • Extrinsic: III, VII
  • Intrinsic: XII, XI, IX, VIII, HMWK, PK
  • Common: X, V, II, I, XIII
• Factor V and VIII are labile factors, easily deteriorate and disintegrate
• The inactive clotting factor will act as the substrate
• Transaminase


  Transferases that transfer a particular group
• For a product to be formed, you will need a substrate
• If the collagen is exposed because of the negative charge


  Factor XII will be attracted to that negative charge, which will later on be cleaved or activated
• Contact group

  Once they come into contact with a negative charge, they become activated
• Most significant substrate is Factor I or Fibrinogen
• Plasma contains fibrinogen, making it an ideal specimen for coagulation tests
• VWF aids in the adhesion and aggregation of platelets
• Clotting factors can be characterized as to their functions

  • Enzyme, cofactors, substrate
• Serine protease


  Every enzyme has its own active site rich with serine
• Clotting factors can be classified as to their physical properties

  • Contact group, prothrombin group, fibrinogen group
• Factor II or prothrombin when activated is commonly referred to as "IIa"
• Factor VIII requires Von Willebrand Factor as a carrier protein to become stable within the circulation
• Factor VI is the same as Factor V
• Factor IV (calcium) is not included in the table as it is always present in every step
• The letter “a” beside the clotting number indicates it is active
• Fibrinogen group


  Consists of clotting factors consumed when forming a clot, not associated with the clot itself after job is done
• 80% of Factor II is consumed during coagulation
• Clotting Factors Activation

  1. Inactive clotting factor acts as the substrate

  2. Fibrinogen is the most significant substrate

  3. The letter “a” beside the clotting number means that it is active

  4. Once Factor II or prothrombin is activated, it is commonly referred to as “thrombin”

  5. Once factor I (fibrinogen) is cleaved, "fibrin" or "clot" is written
• Thrombomodulin, protein S, and protein Z inhibit clotting