Hemostasis Pharmacology

  1. Major components of the hemostatic system:
    • Vascular endothelium
    • Platelets
    • Coagulation system
    • Fibrinolytic system
  2. Von Willebrand Factor is produced by which cell?
    Endothelial cell
  3. Which layer of the blood vessel could you find collagen fiber and tissue factor?
    Subendothelial layer
  4. What is the significance of the subendothelial layer of the blood vessel?
    • Promotes coagulation with collagen fiber and tissue factor when exposed to blood (often due to injury to blood vessel)
    • Collagen -> activate platelets
    • Tissue factor -> activate coagulation pathway
  5. All blood vessels are lined by a flat sheet of ______; intact surface is _______ (characteristic relating to clotting)
    • Endothelial cells
    • Antithrombotic
  6. How does endothelial cell achieve thrombo-resistance?
    It forms a physiologic barrier between circulating platelets and clotting factors, and subendothelial substances (collagen and tissue factors)
  7. What are the two potent vasodilators produced by endothelial cells?
    • Prostacyclin (PGI 2)
    • Nitric oxide (NO)
  8. T/F: vasodilators Prostacyclin and nitric oxide inhibit platelet function
    True; these are produced by the endothelial cells, one of the ways that endothelium exhibit thrombo-resistance
  9. Endothelial cells produce anti-______, anti-______ and pro-_____
    • Antiplatelets (ie NO and PGI2)
    • Anticoagulant
    • Profibrinolytic (ie t-PA)
  10. In response to an injured blood vessel, vaso____ occurs
  11. What are the three mediators released by platelet in response to vessel injury?
    • Platelets secrete:
    • Serotonin
    • Thromboxane A2
    • Epinephrine
  12. Epinephrine and serotonin are vaso____
  13. Prostacyclin and nitric oxide are vaso_____, produced by _____. Epinephrine and serotonin are vaso____ released by _____.
    • Vasodilators produced by endothelial cells
    • Vasoconstrictors produced by platelets
  14. What is the mechanism that leads to platelets getting activated when there is injury to the vessel?
    Exposure of blood to subendothelial collagen and tissue factor activates platelets and coagulation pathways
  15. Primary hemostasis involves which cell?
  16. In primary hemostasis, platelets first _____, then changes shape to ____. Once that occurs, platelets release _______, thereby ______ other platelets and aggregate
    • Adhere to the collagen
    • Activate themselves by making thromboxane
    • ADP from granules and thromboxane (produced by platelets)
    • Recruit and activate
  17. Life span of platelets is ____ days
  18. What are the two platelet cytoplasmic granules?
    • Alpha granules contain fibrinogen and clotting factors V and VIII (5 and 8)
    • Dense granules (delta granules) contain ADP, ionized calcium, serotonin and epinephrine
  19. Platelets- alpha granules contain:
    Fibrinogen, clotting factors V and VIII
  20. Platelets- dense granules contain:
    ADP, ionized calcium, serotonin and epinephrine
  21. Platelet adhesion to collagen direct pathway:
    Platelet receptors Gp1a-2a (glycoprotein), and Gp VI bind directly to subendothelial collagen tissue
  22. Platelets adhesion to collagen indirect (major site) way:
    Platelets bind indirectly to collagen tissue (subendothelial layer) via GP1b to von Willebrand factor secreted by endothelial cells
  23. What is the major substance needed for platelet adhesion that is secreted by endothelial cells?
    Von Willebrand factor
  24. How is thromboxaneA2 produced?
    Upon adhering to collagen, platelets will change shape (activating Gp2b/3a) and this shape change exposes phospholipid membrane which is precursor to thromboxane synthesis
  25. T/F: When blood reaches subendothelial collagen, platelets get signaled to come bind to the endothelium
    False; platelets binds to the subendothelial collagen via GP1b to vWF, as well as to collagen directly via GP6 and GP1a and 2a
  26. Thrombin is factor___, and this causes vaso_____
    • IIa
    • constriction
  27. Major stimulators of platelet activation:
    • Thromboxane A2
    • ADP (From dense granule)
    • Thrombin (formed from phospholipid membrane, like TxA2)
  28. What receptor on the activated platelets form bridging crosslinks with fibrinogen?
    • GP2b/3a
    • vWF can also help to form these bridging crosslinks in high shear blood flow conditions
  29. What is the significance of crosslinking fibrinogen via GP2b/3a?
    Leading to platelet aggregation
  30. What can inhibit platelet aggregation?
    Nitric oxide and prostacyclin produced by endothelial cell inhibit platelet aggregation and cause vasodilation
  31. Most clotting factors are made in the _____
  32. Liver needs _____ to make 4 clotting factors:
    • Vitamin K
    • Factors II, VII, IX, X.
  33. What are two natural anticoagulants formed by the liver requiring Vitamin K?
    • Protein C
    • Protein S
  34. T/F: Clotting factors circulate in the blood in the active form
    False-mostly; circulating clotting factors are in inactive form. Except actually for Factor VII (7) that one is actually in its active form In the blood
  35. T/F: vitamin K dependent clotting factor needs vitamin K to be oxidized so the precursor molecule (glutamic acid) gets de-carboxylated and this allows a calcium molecule to interact with it to anchor the factor to phospholipid membrane of activated platelets
    False; glutamic acid gets carboxylated.
  36. Secondary hemostasis:
    Formation of a fibrin clot- cement platelet plug in place
  37. Coagulation cascade: contact activation pathway is ____ pathway. Tissue factor pathway is the ___ pathway.
    • Intrinsic
    • Extrinsic
  38. Tissue factor is factor ___. Calcium is factor ___
    • III
    • IV
  39. Extrinsic and intrinsic pathways converge at the activation of factor _____ into the ___ pathway which activates ____ and leading to ___
    • X
    • Common
    • Ia
    • Cross-linked fibrin clot
  40. Extrinsic pathway: Factors _____
    VII and Tissue factor (III)
  41. Intrinsic pathway: factors____
    • XII
    • XI
    • IX
    • VIII
  42. What is the Hageman factor?
    Factor XII, part of the intrinsic factor
  43. T/F: the intrinsic pathway is the most physiologically relevant pathway for the initiation of coagulation
    False; the extrinsic pathway is, not the intrinsic pathway. Extrinsic pathway is activated by tissue factor (F III) expressed at sites of injury vs intrinsic pathway is when blood interacts with a negatively charged surface like glass
  44. Warfarin is monitored via ___ coagulation tests reported as____, associated with ____ pathway
    • PT
    • INR
    • Extrinsic
  45. T/F: The intrinsic pathway should not be completely ignored even though it is relatively unimportant, but patients with coronary catheter and other blood-contacting medical devices could likely have activation of this intrinsic pathway
  46. Blood clotting can be prevented by _____
    Calcium chelators such as EDTA
  47. In initiation phase, small amount of thrombin are formed, what do these thrombin go on to make?
    Mainly Factors 5a, 8a, 11a and up-regulation of platelets
  48. Tissue factor pathway inhibitor would disrupt which phase of coagulation?
    Initiation phase would be turned off
  49. Following the initiation phase comes the ____ phase, which takes place on _____.
    • Amplification
    • Activated phospholipid membrane of the platelets
  50. Major cofactor of intrinsic tenase is ______
    Factor 8a
  51. In amplification phase, Factor ___ from _____ tenase comes to the intrinsic tenase, requiring cofactor _____. And this would produce factor _____ which goes to the ________ , joining factor ____ which leads to ___ burst
    • Factor IX
    • Extrinsic
    • Factor VIIIa
    • Factor Xa
    • Prothrombinase
    • Factor Va (co-factor/accelerator)
    • Thrombin
  52. 4 main things needed for thrombin burst during amplification phase:
    • Factors 5a, 10 a, 2a
    • And calcium
  53. Formation and growth and stabilization of fibrin clot is the _____ phase
  54. Function of thrombin in the propagation phase?
    • Convert fibrinogen to fibrin
    • Activates factor XIIIa
  55. Which factor is in charge of crosslinking fibrin polymers?
    Factor XIIIa
  56. Co-factor, enzyme and product of Extrinsic tenase, intrinsic tenase and prothrombinase:
    • Extrinsic tenase: tissue factor, Factor VIIa, Factors IXa and Xa (co-factor, enzyme, product)
    • Intrinsic tenase: facot VIIIa, Factor IXa, Factor Xa
    • Prothrombinase: Factor Va, Factor Xa, Thrombin (Factor IIa)
  57. How does fibrinolysis occur?
    Endothelial cell makes plasminogen activator (t-PA) which activates fibrinolysis
  58. How does plasminogen gets converted into plasmin?
    Upon binding to fibrin, it can be converted to plasmin by plasminogen activator (t-PA)
  59. T/F: Plasminogen is a zymogen of plasmin that is produced in the kidneys
    False; it is produced in the liver and circulates in the blood in a form that is activation-resistant
  60. What is the function of alpha2-antiplasmin?
    Pick up free plasmin that has escpeted the site
  61. What is D-dimer?
    It is a fibrin degradation product. That’s why we test for D-dimer to see whether there is clot
  62. Thrombin can activate Protein _____, which is a natural____. And it will bind to co-factor Protein _____ forming a complex which will inactivated Factor _____ and Factor _____. This will lead to inhibition of further blood coagulation
    • Protein C
    • Anticoagulant
    • Protein S
    • Factor VIIIa
    • Factor Va
  63. Thrombin can bind to _____ expressed on the endothelial cells, which will inactivate thrombin, and activate ____
    • Thrombomodulin
    • Protein C (a natural anticoagulant)
  64. Antithrombin III binds to ____ on endothelial cells and inhibits the activity of ______ and factors ___, ____, ___, _____.
    • Heparan (heparin-like molecules)
    • Thrombin
    • IXa, Xa, XIa, and XIIa
  65. What are the 7 ways of controlling blood clotting?
    • 1 factors activation is restricted to sites of exposed phospholipids
    • 2 Antithrombin III presence to inhibit thrombin and 9a, 10a, 11a, 12a
    • 3 Thrombomodulin binds and inactivate thrombin
    • 4 activating protein C and S which inactivate Va and VIIIa
    • 5 endothelial secrete Tissue factor pathway inhibitor that inactivate factor 10a and TF-VIIa complexes
    • 6 endothelial secretion of NO and prostacyclin inhibit platelet aggregation
    • 7 activation of fibrinolysis by endothelial secretion of TPA
Card Set
Hemostasis Pharmacology
HemeOnc Final