coag2

Clotting Factors: Drug Target Sites


Factor/Component	also called	Target
I	Fibrinogen
II	Prothrombin	Heparin (IIa); Warfarin (synthesis)
III	Tissue Thromboplastin
IV	Calcium
V	Proaccelerin
VII	Proconvertin	Heparin (VIIa); Warfarin (synthesis)
VIII	Antihemophilic globulin (AHG)
IX	Christmas factor, plasma thromboplastin component (PTC)	Heparin (IXa); Warfarin (synthesis)
X	Stuart-Prower factor	Heparin (IXa); Warfarin (synthesis)
XI	Plasma thromboplastin antecedent (PTA)
XII	Hageman factor
XIII	Fibrin-stabilizing factor
Proteins C and S	-------	Warfarin (synthesis)
Plasminogen	-------	Thrombolytic enzymes, aminocaproic acid

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Coagulation and Fibrinolysis: Regulation

Regional blood coagulation must be discreet in order to:
- not impair blood flow excessively
- avoid disseminated clotting
Systems regulating coagulation:
- Fibrin inhibition
- Fibrinolysis

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Inactivation of coagulation proteins (away from injury site)
- Plasma Protease Inhibitors:
  - a₁-antiprotease
  - a₂-macroglobulin
  - a₂-antiplasmin
  - antithrombin III
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- -----Failure of plasma protease inhibitor system: ----- Disseminated Intravascular Coagulation (DIC)-- may occur following:
  - obstetrical emergencies (abruptio placentae; bacterial sepsisreprint
  - major tissue injury
  - cell lysis: neoplastic disease

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Fibrinolysis:
- Major process: conversion plasminogen (inactive) ® plasmin (proteolytic enzyme, active)
- plasminogen activators: released from damaged cells
- Plasmin:
  - limits thrombosis extension (by proteolytic fibrin digestion)
- Drug interventions: fibrinolytic system:
  - Activators of fibrinolysis:
    - tissue plasminogen activator (t-PA)
    - urokinase (Abbokinase)
    - streptokinase (Streptase, Kabikinase)
  - Inhibitors of fibrinolysis:
    - aminocaproic acid (Amicar)

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Primary Reference: O'Reilly, R.A. Drugs Used in Disorders of Coagulation, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 916-940

Handlin, R.I. Bleeding and Thrombosis, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 339-344.