Ch. 23 Notes

  1. Hemostasis
    • Hemorrhage + Clotting
    • Balance between the two
  2. Four components of the Hemostasis System
    • Vasculature (blood vessels)
    • Thrombocytes (Platelets)
    • Plasma coagulation proteins
    • Fibrinolytic system (Inhibits/removes clots)
  3. Basic Hemostasis sequence after a cut:
    • Vasoconstriction: Blood vessels diameter decreases
    • Formation of platelet plug at damaged site
    • Platelet--Plasma protein--vasculature
    • Fibrin clot formation
    • Clot removal: fibrinolysis
  4. Arteries
    • Vessels transporting oxygenated blood away from the heart.
    • High BP: 100-120 mm/hg
  5. Veins
    • Vessels transporting de-oxygenated blood back to the heart
    • Veins are thinner and weaker than arteries
    • Low BP: 60-80 mm/Hg
  6. Capillaries
    • middle ground between arteries and veins
    • oxygen delivered to the cells
    • Very thin, only a single cell layer thick
  7. Tunica intima
    • Innermost
    • Single endothelial cell layer in contact with blood
    • Underneath lies collagen
  8. Tunica Media
    Middle layer of smooth muscle and elastic tissue
  9. Tunica adventia
    • Outer layer
    • Connective tissue nerve endings, and the vas vasorm (layers of tissue on outside)
  10. Functions of the endothelial lining
    • If intact, then inert with blood components
    • If traumatized then physiologically active
    • First: Responder to injury (vasoconstriction)
    • Synthesis and stores active chemicals
    • Prostacyclins: inhibit platelet aggregation and adhesion)
    • Plasminogen activators: Clot dissolution
    • Von Willebrand Factor: platelet adhesion protein
    • Collagen activates plasma coagulation proteins: Factor 7
  11. Hemostasis related substances f/endothelium:
    • Collagen: Binds to platelet membrane GP Ib/IIa
    • vWF: Binds to platelet membrane GP Ib/IIa
    • PG12: Prostacyclin inhibits plt. aggregation
    • Tissue factor: Liproprotein activates plasma coagulation protein
    • Thrombomodulin: Protein C cofactor (inhibits fibrin formation)
    • TPA: starts fibrinolysis
  12. Disruption of endothelium activates all 4 components
    • Vasculature: Short term vasoconstriction closes small blood vessels and limits blood loss.
    • Platelets: Aggregation and adhesion form small clumps at injured site
    • Plasma proteins: proteins begin formation of an insoluble protein "glue" fibrin clot
    • Fibrinolysis: proteins begin the process of limiting formation, eventual removal of clot.
    • Endoreplication: Cell division without cytoplasmic division (nucleus divides, cytoplasm does not)
  13. Platelet structure
    Fluffy outer coat, regulates shape platelet adhesion and aggregation
  14. Open Canalicular system
    • Sponge like
    • Porous network system that permeates the platelet
    • Releases the cytoplasmic granule contents to the outside.
  15. Microfilaments and microtubules (cytoskeleton)
    Structural proteins
  16. Platelet Granules
    Alpha granules (most abundant)
    vWF (platelet adhesion), fibronectin, thrombospondin (platelet aggregation), platelet fibrinogen, Platelet factor 4
  17. Dense Granules
    • ADP
    • Serotonin (vasoconstriction)
  18. Platelet Kinetics
    • Life span 8-10 days
    • 1 megakarocyte produces 1-2000 platelets. Matures in 5 days
    • 2/3 platelets circulate in blood
    • 1/3 platelets sequestered in spleen
    • Old platelets phagocytized by the RE system (mainly spleen)
  19. Platelet function in hemostasis
    • Endothelium is damaged, platelets will being to interact with exposed sub-endothelium tissues.
    • Platelets are activated by exposure to the sub-endothelium, they lose their disk shapes to form pseudopods that extend and attach to exposed collagen
  20. Platelets "tie up" to collagen and other platelets with proteins that bind with different glycoprotein receptors.
  21. vWF
    • adhesion
    • Epithelial cells
  22. Thrombospondin
    • adhesion
    • Alpha granule
  23. Fibronectin
    • Adhesion
    • Alpha granule
  24. Vitronectin
    • Adhesion
    • Alpha granules
  25. Fibrinogen
    Plasma and Platelets
  26. Glycoprotein receptors
    GP IIb/IIIa
    Attaches to other platelets with Fibrinogen
  27. GP Ib
    Attaches to collagen with vWF
  28. Adhesion
    Platelets "stick" to the surfaces of damaged blood vessels
  29. Aggregation
    • Platelets sticking to each other at the damaged vessel
    • Promoted by: Collagen, Thrombin, Serotonin, TXA2
    • Inhibited by: Aspirin, Some prostaglandins
  30. Aspirin
    • Impairs the synthesis of thromboxane (TXA2), stimulates platelet granule release.
    • Platelet aggregation is impaired for the entire life span of the platelet.
    • Commonly prescribed to inhibit vascular occlusions (clots) in patients at risk for coronary occlusions
    • Effect on platelet's take place within 5-15 minutes after ingestion.
  31. Plavix
    • Inhibits platelet GP IIb/IIIa
    • When people die from hemostasis disorders, they usually die from excessive clotting
  32. Quantitaive and Qualitative Platelet Tests
    • A normal platelet count does not necessarily imply normal function.
    • Excessive bruising or bleeding with a normal platelet count suggests a qualitative platelet disorder.
  33. Thrombocytopenic patients can be transfused with platelets
  34. Blood (plasma) coagulation proteins
    • Synthesized in liver
    • "Cascading-domino" sequence of chemical interactions between the proteins, tissue substances and calcium leads to the formation of an insoluble protein-the fibrin clot at the site of the injured blood vessel.
    • The fibrin clot seals off the damaged blood vessel and limits blood loss.
    • Other proteins in the fibrinolytic system limit fibrin formation and eventually its dissolution.
  35. Activated Factor IIa
  36. Inactivated Factor II
  37. Coagulation proteins can be measured
    • Individually (factor assays test, fibrinogen)
    • Collectively (PT and PTT tests)
  38. Group I Fibrinogen
    • Consumed during clotting (absent in serum)
    • Factors 5 and 8 extremely liable
    • Increased in inflammation, pregancy, and oral contraceptives
  39. Group IIĀ 
    Prothrombin Group
    2,7,9, 10
    • Not consumed during clotting (except 2)
    • Requires Vitamin K for synthesis
  40. Group III
    Contact Group
    (11, 12, PK, HMWK)
    • PK=Fletcher
    • HMWK=Fitzgerald
    • Not consumed during clotting
    • Stable storage
  41. Factor I
    • Soluble plasma protein precursor to fibrin
    • Fibrinogen--Fibrin clot
  42. Factor II
    • Stable precursor of thrombin
    • Prothrombin---Thrombin
  43. Factor IIa
    • Active form of prothrombin
    • Thrombin converts fibrinogen--fibrin
    • Promotes platelet aggregation
  44. Thromboplastin
    Any tissue (non-plasma) phospholipid substance (cell membrane guts)
  45. Ionized Calcium
    • Electrolyte
    • Only ionized Ca is active in hemostasis
  46. Factor V
    • Very liable (1/2 life=16 hours)
    • Consumed during clotting
  47. Factor VIII
    Anti-Hemophiliac Factor
    • 2 Complex components
    • High Molecular Weight: vWF, VIII RCo (Platelet aggregation), VIII Ag (Antigenic site)
    • Low Molecular Weight: VIII C (Procoagulant), VIII Ag (Antigenic Site)
  48. Factor VII
  49. Factor IX
    Plasma Thromboplastin Component
  50. Factor X
    Stuart Factor
  51. Factor XI
    Plasma Thromboplastin Antecedent
  52. Factor XII
    Stuart Factor
  53. Factor XIII
    Fibrin Stabilizing Factor
  54. Mechanisms of the coagulation proteins
    Goal=Fibrin clot
  55. Three pathways
    Extrinsic Pathways
    Activated by contact with tissue phospholipids following endothelial damage.
  56. Intrinsic pathway
    Activated by contact with negatively charged solid surfaces (collagen, glass)
  57. Common pathway
    Represents the merging of the extrinsic and intrinsic pathway
  58. Fibrin Formation
    Fibrinogen--(thrombin)---Fibrin Monomers--- Fibrin
  59. Proteolysis
    Thrombin splits fibrinogen into smaller parts
  60. Polymerization
    Monomers polymerize using (weak) hydrogen bonds
  61. Stabilization
    Factor 13 promotes stronger covalent bonding between monomers forming a strong fibrin polymer
  62. Platelets trapped in the fibrin extend pseudopods to fibrin strands and pull the strands together--clot retracts and becomes stronger
  63. Fibrinolysis
    (Limitation and dissolution of the Fibrin clot)
    • Plasminogen----Plasmin
    • Plasminogen activators can include such substances as endothelial cell enzymes, bacterial products.
    • Plasmin, enzyme that breaks fibrin and fibrinogen into small pieces.
    • Pieces are fibrin degradation products (X, Y, D,E)
  64. FDP
    • Inhibit platelet aggregation, fibrin, fibrin polymerization.
    • Plasminogen activators can be used to treat AMI's pulmonary emboli and other vascular occlusion.
  65. FDP testing
    • Special tube in kit.
    • Serum specimen
    • Fibrinolytic activity of plasmin--fibrinogen and fibrin into small fragments
    • DIC, DVT, PE have presence of FDPs
    • Latex particles coated with anti-fibrinogen.
    • No agglutination in either tube: < 10 ug/ml
    • Agglutination in 1:5: 10-20 ug/ml
    • Test doesn't differentiate between Primary and Secondary because it uses an anti-fibrinogen antibody that reacts with FDPs and fibrinogen.
  66. Normal Mechanisms against thrombosis
    normal blood flows limits the concentration of pro-coagulants at the injury site.
  67. Natural anticoagulants
    AT III
    • Most active natural anticoagualnt
    • Inhibits thrombin (9,10,11,12)
    • Synthesize by liver, platelets, endothelium
  68. Protein C
    • Inhibits Factor 5,8
    • Synthesized by liver (vitamin K dependent)
  69. Protein C and S
    • Both Natural anticoagulant
    • Protein C-Protein S pathway a major system involved in the regulation of blood coagulation and in the protection against thrombotic diseases.
    • Congenital or acquired Protein C and Protein S deficiencies, causes recurrent thrombotic diseases, in the absence, in the absence of any obvious underlying cause.
    • Factor 5 mutation: results in a prolonged survival of thrombotic activated Factor 5, following stimulation of the coag cascade, and increases the risk of thrombosis.
  70. People who keep making too many clots, mutation in 5, didn't respond to Protein C or natural anticoagulation.
  71. Therapeutic Anticoagulants
    Blood thinner
    • PT measures
    • Oral anticoagulants
    • Effective for long term, self-medication
    • Vitamin K antagonists
    • Group 2 (2,7,9,19)
    • Slow acting (8-12 hour before effects)
    • Long acting
  72. Wisconsin Alumini Research Foundation
    Originally utilized as rat poison after research into the unexplained deaths of cows during 1920s discovered a naturally occuring substance that caused internal bleeding
  73. Heparin
    • PTT measured
    • IV anti-coagulant
    • Given in hospital
    • Inactivates factors IIa and Xa
    • Fast acting
    • Short duration (1/2 life=one hour)
    • Standard dose acheived when the PTT is 1.5 times the baseline
Card Set
Ch. 23 Notes
Coagulation Notes