by FDA, are heparinoids, Lepirudin (recombinant hirudin), Fon daparinux (pentasaccharides), Arga-troban, and Bivalirudin.


Coumadin is a vitamin K antagonist drug that inhibits the vitamin K-dependent coagulation factors. Warfarin is a Coumadin derivative that is widely used in the United States as an oral anticoagulant drug. Warfarin inhibits carboxylation of the vitamin K-dependent factors (II, VII, IX, X) as well as vitamin K-dependent anticoagulant proteins such as protein C and protein S. The half-life of warfarin is about 36 hours.1 Warfarin is given orally as a long-term anticoagulant. Warfarin dosage varies from patient to patient and depends on dietary stores of vitamin K, liver function, preexisting medical conditions, and concurrent medications. Warfarin therapy is monitored by PT/international normalized ratio (INR).

The INR is a method to standardize PT assays against differences in commercial thromboplastin reagent.10 The INR was established by the World Health Organization (WHO).1 Each thromboplastin reagent is calibrated against a WHO reference preparation. The INR is calculated using the following formula: INR = (PT ratio)ISI, where ISI refers to the international sensitivity index, which is calculated for each thromboplas-tin reagent against a reference thromboplastin reagent.1

According to the American College of Chest Physicians' consensus panel, the therapeutic range of INR is 2.0 to 3.0 for the treatment of venous thromboembolism. For prosthetic mechanical heart valves and prevention of recurrent MI, a higher dose of warfarin is required to attain an INR of 2.5 to 3.5.1

The most common adverse effect of Coumadin therapy is bleeding, which is directly dose related.10 Patients with an INR of greater than 3.0 are at the higher risk of bleeding. Warfarin crosses the placenta and therefore should be avoided during pregnancy. Another rare but devastating complication of warfarin therapy is skin necrosis. This phenomenon mostly occurs in patients who receive high doses of warfarin and may have heterozygous protein C deficiency.1 Skin necrosis is caused by the rapid drop in protein C in patients who have preexisting protein C deficiency resulting in a thrombotic state.1

Thrombolytic Drugs

Thrombolytic drugs are commonly used in acute arterial thrombosis for immediate thrombolysis, restoration of vascular integrity, and prevention of tissue and organ damage. Most fibrinolytic drugs are made by recombinant techniques and are fashioned after tPA and urokinase. Urokinase is not fibrin specific and causes hypofibrinogenemia by the breakdown of fibrinogen. Urokinase can be used for the treatment of venous thromboembolism, MI, and thrombolysis of clotted catheters.1 Streptokinase is a thrombolytic agent obtained from beta-hemolytic streptococci. Streptoki-

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