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2013-05-02 23:58:33
Intro Hemostasis Fibrinolytic System Regulatory Proteins

Intro to Hemostasis, Fibrinolytic System, Regulatory Proteins
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  1. What occurs during Primary Hemostasis?
    • Vascular system and platelets are involved by coming in contact with exposed collagen...
    • Small blood vessels constrict
    • Platelets begin to aggregate
    • Platelet receptor sites are exposed
  2. What is the function of ADP/ATP?
    • Promotes platelet aggregation
    • Acts as an energy source
  3. What is the function of Thromboxane A2?
    Promotes acitvation, release, and aggregation
  4. What is the function of serotonin when dealing with platelet function?
    Promotes vasoconstriction
  5. What happens during Secondary Hemostasis?
    • Goal is generation of sufficient thrombin to convert fibrinogen to fibrin clot
    • Activation of intrinsic, extrinsic, and common coag pathways
    • Fibrin clot
  6. What is included in the fibrin clot?
    • Platelet plug formed in the primary hemostasis
    • Fibrin formed in secondary hemostasis
  7. Write down the coag pathway (intrinsic, extrinsic, and common)
  8. What does the Intrinsic Pathway include?
    • XII (Hageman or Contact Factor)
    • XI (Plasma thromboplastin)
    • Prekallikrein (Fletcher)
    • HMWK (Fitzgerald)
    • IX (plasma thromboplastin component or Christmas factor)
    • VIII (Anti-hemophiliac Factor)
  9. How does the Extrinsic Pathway work?
    Release of tissue factor from injured blood vessel endothelial cells and subendothelium
  10. What is included in the Extrinsic Pathway?
    • III (Tissue Thromboplastin¬†factor)
    • VII (Stabile Factor)
  11. How does the Common Pathway work?
    Factor X Activation by either the extrinsic or intrinsic pathway
  12. What does the Common pathway include?
    • X (Stuart-Prower)
    • V (Proaccerlerin or labile factor)
    • II (Prothrombin)
    • I (Fibrinogen)
    • XIII (fibrin/clot¬†stabilizing factor)
  13. What is another name for Factor IV?
  14. What is another name for von Willebrand Factor?
    Ristocetin cofactor
  15. What else are coag factors known as?
    Enzyme precursors or zymogens
  16. What are zymogens?
    Zymogens are substrates having no biologic activity until converted by enzymes to active forms called serine proteases
  17. What are included in the zymogens?
    • II (Prothrombin)
    • VII (Stabile Factor)
    • IX (Christmas Factor)
    • X (Stewart Prower Factor)
    • XI (Plasma Thromboplastin Antecedent)
    • XII (Hageman or Contact Factor)
    • Prekallikrein
  18. What are included in the serine proteases?
    • IIa
    • VIIa
    • IXa
    • Xa
    • XIa
    • XIIa
    • Kallikrein
  19. What is the only substrate in the cascade that does NOT become an activated enzyme?
  20. What coag factors are included in the Contact group and where are they produced?
    • Prekallikrein
    • HMWK (high molecular weight kininogen)
    • XI (Plasma Thromboplastin Antecedent)
    • XII (Hageman or Contact Factor)
    • Produced in the liver
  21. What is the function of the Contact group?
    • XII and prekallikrein reciprocally activate each other and HMWK is a cofactor for this process
    • All play a role in the intrinsic coag activation
    • XIIa, kallikrein, and HMWK play a role in the inflammatory response, intrinsic fibrinolytic activation, kinin formation, and activation of the complement system
  22. What factors are included in the Prothrombin group and where are they produced?
    • II (Prothrombin)
    • VII (Stabile Factor)
    • X (Stewart Prower Factor)
    • Produced in the liver
  23. What is required for synthesis of functional coag factors?
    • Vitamin K is required for synthesis of functional factors
    • Calcium binding sites are necessary for binding to phospholipid (PF3) surfaces
  24. Name some causes for synthesis of nonfunctional coag factors
    • Vitamin K deficiency
    • Antibiotics that kill the intestinal bacterial flora responsible for vitamin K synthesis
    • Oral anticoagulants (warfarin/coumadin) that interfere with the metabolism of vitamin K (vitamin K antiagonists)
  25. What coag factors are included in the fibrinogen group and where are they produced?
    • I (Fibrinogen)
    • V (Labile Factor)
    • VII (Stabile Factor)
    • XIII (Fibrin/clot Stabilizing Factor)
    • Produced in the liver
  26. What happens when there is low thrombin levels?
    Low thrombin levels activate factors V, VIII, and XIII; and also induce platelet aggregation
  27. What happens when thrombin levels are high?
    Thrombin binds to thrombomodulin on the endothelial cell surface and activates the protein C pathway
  28. What does activated protein C and its cofactor protein S do?
    Inhibit factors V and VIII
  29. What are the steps for the conversion of fibrinoen to fibrin?
    • Fibrinogen alpha and beta fibrinopeptides are cleaved by thrombin, forming soluble fibrin monomers
    • Fibrin monomers spontaneously polymerize, forming soluble fibrin polymers - which is the end point for clot based tests
    • Clot stabilization occurs, requiring thrombin activation of XIII and calcium
  30. Where is Factor VIII synthesized?
  31. What is Factor VIII composed of?
    • VIII:C (antihemophilic factor): the coag portion that acts as a cofactor in the intrinsic coag pathway
    • VIII:Ag: the antigenic property of factor VIII
  32. What are the 2 coag factors that are deficient in Hemophilia A?
    • VIII:C
    • VIII:Ag
  33. Where is von Willebrand factor (vWF) synthesized?
    • Endothelial cells
    • Megakaryocytes
  34. What is the function of vWF:RCo (ristocetin cofactor)?
    • Needed for platelet adhesion to collagen in vivo
    • Needed for a normal response to ristocetin on aggregation studies in vitro
  35. What 2 coag factors are deficient in von Willebrand disease?
    • vWF:RCo
    • vWF:Ag
  36. What acts as the carrier protein for factor VIII:C?
    vWF subunits polymerize to form multimers of varying sizes
  37. What is the function of the complement system when activated during coagulation and finbrinolysis?
    Lysing antibody-coated cells
  38. How is complement activation regulated?
    Regulated by C1 inactivator
  39. What is included in the kinin system?
    • XII (Hageman or Contact Factor)
    • XI (Plasma Thromboplastin Antecedent)
    • Prekallikrein (Fletcher factor)
    • HMWK (Fitzgerald factor)
  40. What is the function of the kinin system?
    • Involved in chemotaxis and pain sensation
    • Mediates inflammatory response, promotes vasodilation, and activator of intrinsic coag and complement pathways
  41. What does the fibrinolytic system do?
    • Keeps blood vessels clear
    • Important in clot dissolution
    • During this process, plasminogen is activated to plasmin
  42. Where is plasminogen produced?
  43. Name the activators that convert plasminogen to plasmin
    • Intrinsic activators: XIIa, kallikrein, HMWK
    • Extrinsic activators: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA)
    • Exogenous activators (therapeutic agents): t-PA, streptokinase, urokinase, etc (drugs administered to lyse existing clots)...
  44. What is not normally found in circluation
    Its' precursor is found in circulation
    Degrades fibrin clots (fibrinolysis), fibrinogen (fibrinogenolysis), factors V and VIII
    Activates complement system
  45. What regulatory protein:
    Produced in the liver
    Principal inhibitor of coagulation
    Inhibits the serine proteases
    Therapeutic heparin enhances the action of this protein
    Antithrombin (AT)
  46. What regulatory protein:
    Vitamin K-dependent regulatory proteins
    Activated when thrombin binds to thrombomodulin on the endothelial cell surface
    Inhibits factors V and VIII to provide negative feedback on the cascade
    • Protein C
    • Protein S
  47. What regulatory protein inhibits factor VIIa-tissue factor complex?
    Tissue factor pathway inhibitor
  48. What regulatory protein inhibits thrombin, Xa, kallikrein, and plasmin?
  49. What regulatory protein inhibits XIa and inactivates plasmin?
  50. What regulatory protein inhibits C1 from the complement cascade, XIIa, XIa, kallikrein, and plasmin?
    C1 inhibitor
  51. What regulatory protein:
    Is the principal inhibitor of fibrinolysis
    Neutralizes plasmin
  52. What regulatory protein:
    Important inhibitor of fibrinolysis
    Prevents activation of plasminogen by t-PA
    Released from endothelial cells upon damage
    PAI-1 (plasminogen activator inhibitor-1)