The drugs used in clotting and bleeding disorders fall into 2 major groups: (1) drugs used to decrease clotting or dissolve clots already present in patients at risk for vascular occlusion and (2) drugs used to increase clotting in patients with clotting deficiencies. The first group, the anticlotting drugs, includes some of the most commonly used drugs in the United States. Anticlotting drugs are used in the treatment and prevention of myocardial infarction and other acute coronary syndromes, atrial fibrillation, ischemic stroke, and deep vein thrombosis (DVT). Within the anticlotting group, the anticoagulant and thrombolytic drugs are effective in treatment of both venous and arterial thrombosis, whereas antiplatelet drugs are used primarily for treatment of arterial disease.
Anticoagulants inhibit the formation of fibrin clots. Three major types of anticoagulants are available: heparin and related products, which must be used parenterally; direct thrombin and factor X inhibitors, which are used parenterally or orally; and the orally active coumarin derivatives (eg, warfarin). Comparative properties of the heparins and warfarin are shown in Table 34–1.
TABLE 34–1Properties of heparins and warfarin. |Favorite Table|Download (.pdf) TABLE 34–1 Properties of heparins and warfarin.
|Property ||Heparins ||Warfarin |
|Structure ||Large acidic polysaccharide polymers ||Small lipid-soluble molecule |
|Route of administration ||Parenteral ||Oral |
|Site of action ||Blood ||Liver |
|Onset of action ||Rapid (minutes) ||Slow (days); limited by half-lives of preexisting normal factors |
|Mechanism of action ||Activate antithrombin III, which inactivates coagulation factors including thrombin and factor Xa ||Impairs post-translational modification of factors II, VII, IX and X |
|Monitoring ||aPTT for unfractionated heparin but not LMW heparins ||Prothrombin time |
|Antidote ||Protamine for unfractionated heparin; protamine reversal of LMW heparins is incomplete ||Vitamin K1, plasma, prothrombin complex concentrates |
|Use ||Mostly acute, over days ||Chronic, over weeks to months |
|Use in pregnancy ||Yes ||No |
Heparin is a large sulfated polysaccharide polymer obtained from animal sources. Each batch contains molecules of varying size, with an average molecular weight of 15,000–20,000. Heparin is highly acidic and can be neutralized by basic molecules (eg, protamine). Heparin is given intravenously or subcutaneously to avoid the risk of hematoma associated with intramuscular injection.
Low-molecular-weight (LMW) fractions of heparin (eg, enoxaparin) have molecular weights of 2000–6000. LMW heparins have greater bioavailability and longer durations of action than unfractionated heparin; thus, doses can be given less frequently (eg, once or twice a day). They are given subcutaneously. Fondaparinux is a small synthetic drug that contains the biologically active pentasaccharide present in unfractionated and LMW heparins. It is administered subcutaneously once daily.