6. Antithrombotic Properties of the Endothelium Anticoagulant properties * HEPARIN-LIKE MOLECULES: activate anti-thrombin III (inactivates active proteases) * THROMBOMODULIN : changes specificity of thrombin (activates protein C , which inactivates factors Va and VIIIa *Endothelial cells produce tPA which activates fibrinolysis via plasminogen to plasmin
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12. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF Extrinsic Pathway IXa VIIIa XIa XIIa Intrinsic pathway XIIIa Soft clot Fibrin Hard clot V VIII
18. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF Extrinsic Pathway IXa VIIIa XIa XIIa Intrinsic pathway
19. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF Extrinsic Pathway IXa VIIIa XIa XIIa Intrinsic pathway XIIIa Soft clot Fibrin Hard clot
20. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF Extrinsic Pathway IXa VIIIa XIa XIIa Intrinsic pathway XIIIa Soft clot Fibrin Hard clot V VIII
21. Hemophilia A Deficiency of/nonfunctional VIII Hemophilia B Deficiency of /nonfunctional IX Why do they bleed?
22. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF Extrinsic Pathway IXa VIIIa XIa XIIa Intrinsic pathway XIIIa Soft clot Fibrin Hard clot V VIII
23. Thrombin (IIa) Prothrombin (II) Xa VIIa TF IXa Revised Coagulation Pathway (Tissue Factor Pathway) IX NB: production of IXa Interaction of intrinsic and extrinsic pathways
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25. Thrombin (IIa) Prothrombin (II) Xa VIIa TF IXa Tissue Factor Pathway Inhibitor IX TFI TFPI NB: Inhibition of Xa and VIIa
26. Production of IXa Production of small amounts of thrombin (IIa) Tissue Factor Pathway Net result: NB: no/little fibrin formed!
28. Fibrinogen Fibrin Thrombin Prothrombin Xa Va VIIa TF IXa VIIIa XIIIa Soft clot Fibrin Hard clot V VIII Tissue Factor Pathway NB: activation of IX by VIIa IX
32. Role of vitamin K Some clotting factors require a post-translational modification before they are active in clotting These factors are II, VII, IX, X, proteins C and S This PTM involves the addition of a COO- to certain Glu residues in the clotting factors This PTM results in the formation of several -carboxy glutamates = Gla This PTM requires vitamin K
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