Hemostasis and Drugs

There are a variety of drugs that affect all aspects of hemostasis; common ones will be mentioned in more detail below. Primary hemostasis: Drugs that have been associated with thrombocytopenia include heparin, antineoplastic agents, gold compounds, propylthiouracil (an antithyroid drug), sulfonamides, and penicillin. Drugs that are used to inhibit platelet function include aspirin, dazoxiben, dipyrimadole, ticlopidine and the newer GPIIb/IIIa antagonists. Decreased platelet function is a side-effect of a variety of drugs, including phenothiazines, dextran, caffeine, aminophylline, antibiotics (cephalosporins, penicillin), antihistamines and barbiturates. Secondary hemostasis: Drugs used to inhibit the coagulation cascade for therapeutic purposes include heparin, hirudin (a specific thrombin antagonist) and warfarin. Topical anticoagulants include topical thrombin and "fibrin glue" (a mixture of cryoprecipitate, thrombin and calcium). Inhibition of the coagulation cascade is a side-effect of some drugs including polysulfated glycosaminoglycans and sulfaquinoxolone (a direct vitamin K antagonist). Tertiary hemostasis: Drugs used for enhancement of fibrinolysis (such as in people with heart attacks) include streptokinase, staphylokinase, urokinase and tissue plasminogen activator. Inhibitors of fibrinolysis include aprotonin, tranexamic acid and epsilonaminocaproic acid. Aspirin: Acetylsalicylic acid irreversibly acetylates platelet cyclo-oxgenase (inhibiting prostaglandin and thromboxane production) and affects platelets for the duration of their lifespan. Aspirin should not be used as an analgesic for dogs with inherited hemostatic disorders, as the effect of the drug persists even after the drug has been withdrawn (for 7 to 10 days). Aspirin can be used to prevent platelet aggregation in dogs predisposed to thrombosis, as long as the thrombosis is due to platelet hyperaggregability. NSAIDs: Non-steroidal anti-inflammatory drugs reversibly inhibit platelet cyclo-oxygenase, hence their effect is eliminated according to the half-life of the drug. Heparin: Heparin acts primarily by potentiating the antithrombotic activity of antithrombin, but also enhances the antithrombin effects of heparin cofactor II. Heparin binds antithrombin, changing its conformation which accelerates its inhibitory activity. High molecular weight heparin fragments have little affinity for antithrombin and minimal inhibition of factor Xa, however they produce severe side-effects of hemorrhage. Low molecular weight heparin fragments have a high affinity for antithrombin, inhibit factor Xa and have minimal side-effects. Thus, they are preferred for use in thrombotic conditions.

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