Medical Pharmacology Chapter 39: Drugs that Influence Coagulation

 

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

• Inactivation of coagulation proteins (away from injury site)

  • Plasma Protease Inhibitors:

    • α₁-antiprotease

    • α₂-macroglobulin

    • α₂-antiplasmin

    • Antithrombin III

  • Failure of plasma protease inhibitor system: ----- Disseminated Intravascular Coagulation (DIC)-- may occur following:

    • Obstetrical emergencies (abruptio placentae; bacterial sepsis)

    • Major tissue injury

    • Cell lysis: neoplastic disease

• 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)

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.