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COAGULATION SYSTEM
Blood Coagulation
• The clotting mechanism involves a cascade of reactions in which
clotting factors are activated.
• Most of them are plasma proteins synthesized by the liver (vitamin K
is needed for the synthesis of factor II, VII, IX and X).
• They are always present in the plasma in an inactive form.
• When activated they act as proteolytic enzymes which activate other
inactive enzymes.
• Several of these steps require Ca++ and platelet phospholipid.
Blood Coagulation
• The ultimate step in clot formation is the conversion of fibrinogen →
fibrin.
Factor X can be activated by reactions in either
of 2 systems:
• An Intrinsic system
• An Extrinsic system
• Once factor X has been activated, it complexes with calcium
ions, PF3, and factor V to form prothrombin activator
Pathway to Thrombin
•Prothrombin activator catalyzes the
transformation of prothrombin to the active
enzyme thrombin
Common Pathways to the Fibrin Mesh
• Thrombin catalyzes the polymerization of fibrinogen into
fibrin
• Insoluble fibrin strands form the structural basis of a clot
• Fibrin causes plasma to become a gel-like trap
• Fibrin in the presence of calcium ions activates factor XIII
that:
Cross-links fibrin
Strengthens and stabilizes the clot
Intrinsic pathway
• The initial reaction is the conversion of inactive factor XII to active
factor XIIa.
• Factor XII is activated in vitro by exposing blood to foreign surface
(glass test tube).
• Activation in vivo occurs when blood is exposed to collagen fibers
underlying the endothelium in the blood vessels.
• The intrinsic pathway begins with the contact factors, factor XII,
HMWK, and prekallikrein, which activates factor XI.
• Activated factor XI can then activate factor IX, which then acts with its
cofactor,factor VIII,to form tenase complex on a phospholipid surface
to activate factor X.
• Activated factor X then combines with its cofactor, factor V, to form the
prothrombinase complex on a phospholipid surface, converting
prothrombin to thrombin.
INTRINSIC SYSTEM
Extrinsic pathway
• Requires contact with tissue factors external to blood.
• This occurs when there is trauma to the vascular wall and surrounding
tissues.
• The extrinsic system is triggered by the release of tissue factor
(thromboplastin from damaged tissue), that activates factor VII.
• The tissue thromboplastin and factor VII activate factor X.
Tissue Factor Pathway
Net result:
• Production of IXa
• Production of small amounts of thrombin (IIa)
EXTRINSIC SYSTEM
Clot retraction
• Clot formation is fully developed in 3-6 min
• Contraction of platelets trapped within the clot shrinks the fibrin
meshwork pulling the edges of the damaged vessel closer together.
• During clot retraction serum is squeezed from the clot.
Coags.pptx

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Coags.pptx

  • 2. Blood Coagulation • The clotting mechanism involves a cascade of reactions in which clotting factors are activated. • Most of them are plasma proteins synthesized by the liver (vitamin K is needed for the synthesis of factor II, VII, IX and X). • They are always present in the plasma in an inactive form. • When activated they act as proteolytic enzymes which activate other inactive enzymes. • Several of these steps require Ca++ and platelet phospholipid.
  • 3. Blood Coagulation • The ultimate step in clot formation is the conversion of fibrinogen → fibrin.
  • 4. Factor X can be activated by reactions in either of 2 systems: • An Intrinsic system • An Extrinsic system • Once factor X has been activated, it complexes with calcium ions, PF3, and factor V to form prothrombin activator
  • 5. Pathway to Thrombin •Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin
  • 6. Common Pathways to the Fibrin Mesh • Thrombin catalyzes the polymerization of fibrinogen into fibrin • Insoluble fibrin strands form the structural basis of a clot • Fibrin causes plasma to become a gel-like trap • Fibrin in the presence of calcium ions activates factor XIII that: Cross-links fibrin Strengthens and stabilizes the clot
  • 7. Intrinsic pathway • The initial reaction is the conversion of inactive factor XII to active factor XIIa. • Factor XII is activated in vitro by exposing blood to foreign surface (glass test tube). • Activation in vivo occurs when blood is exposed to collagen fibers underlying the endothelium in the blood vessels.
  • 8. • The intrinsic pathway begins with the contact factors, factor XII, HMWK, and prekallikrein, which activates factor XI. • Activated factor XI can then activate factor IX, which then acts with its cofactor,factor VIII,to form tenase complex on a phospholipid surface to activate factor X. • Activated factor X then combines with its cofactor, factor V, to form the prothrombinase complex on a phospholipid surface, converting prothrombin to thrombin.
  • 10. Extrinsic pathway • Requires contact with tissue factors external to blood. • This occurs when there is trauma to the vascular wall and surrounding tissues. • The extrinsic system is triggered by the release of tissue factor (thromboplastin from damaged tissue), that activates factor VII. • The tissue thromboplastin and factor VII activate factor X.
  • 11. Tissue Factor Pathway Net result: • Production of IXa • Production of small amounts of thrombin (IIa)
  • 13. Clot retraction • Clot formation is fully developed in 3-6 min • Contraction of platelets trapped within the clot shrinks the fibrin meshwork pulling the edges of the damaged vessel closer together. • During clot retraction serum is squeezed from the clot.