Thromboembolism warfarin therapy

FIGURE 7-9. Initiation of warfarin therapy. INR, International Normalized Ratio PT, prothrombin time. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 391, with permission.)... 

Tab. 4.1 Known causes of individual variability in warfarin therapy in thromboembolism...

Adjunctive use in prophylaxis of thromboembolism after cardiac valve replacement The recommended dose is 75 to 100 mg 4 times/day as an adjunct to the usual warfarin therapy. 

The risk of embolism associated with mechanical heart valves is 2 to 6% per patient per year despite anticoagulation and is highest with valves in the mitral position. Warfarin therapy (INR 2.5 to 3.5) is recommended in these patients. The addition of enteric-coated aspirin (100 mg/d) to warfarin (INR 3.0 to 4.5) in high-risk patients (preoperative atrial fibrillation, coronary artery disease, history of thromboembolism) with mechanical valves decreases the incidence of systemic embolism and death from vascular causes (1.9 vs. 8.5% per year), but increases the risk of bleeding. 

Rheumatic mitral valve disease is associated with thromboembolic complications at reported rates of 1.5 to 4.7% per year the incidence in patients with mitral stenosis is approximately 1.5 to 2 times that in patients with mitral regurgitation. The presence of atrial fibrillation is the single most important risk factor for thromboembolism in valvular disease, increasing the incidence of thromboembolism in both mitral stenosis and regurgitation four- to sevenfold. In current practice, patients with nonrheumatic atrial fibrillation at low risk for thromboembolism based on clinical characteristics frequently are treated with aspirin. Warfarin therapy is considered in higher-risk patients, especially those with previous thromboembolism and in whom anticoagulation is not contraindicated due to preexisting conditions. 

Warfarin monotherapy is an unacceptable choice for the acute treatment of VTE because it does not produce a rapid anticoagulation effect and is associated with a high incidence of recurrent thromboembolism. However, warfarin is very effective in the longterm management of VTE and should be started concurrently with UFH, LMWH, or fondaparinux therapy. The acute treatment regimen should overlap with warfarin therapy for at least 5 days and until a therapeutic INR has been achieved. The initial dose of warfarin should be 5 to 10 mg (see Fig. 19-8), and it should be adjusted periodically to achieve and maintain an INR between 2.0 and 3.0. 

Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003 348 1425-1434. 

Warfarin has been the mainstay of oral anticoagulant therapy for many years, principally for atrial fibrillation, mechanical heart valves, or venous thromboembolism. Adverse-effects profile of patients on warfarin therapy parallel what would be seen in vitamin K deficiency. Dne to its inhibitory effect on VKOR in the liver, warfarin affects the fnnction of the MGP and has been associated with vascular calcification in various animal and human studies. 

Patients with cancer who develop a venous thromboembolism may benefit from long-term therapy with a low molecular weight heparin (at least the first 3-6 mo of pharmacotherapy) instead of oral warfarin... 

Carter BL. Therapy of acute thromboembolism with heparin and warfarin. Clin Pharm 1991 10 503-18. 

The appropriate duration of warfarin maintenance therapy requires careful consideration of the circumstances surrounding the initial thromboembolic event, the presence of ongoing thromboembolic risk factors, and the risk of bleeding. A major consideration in... 

Anticoagulant therapy, chiefly warfarin, and platelet inhibitors, such as aspirin, are used prophylactically to prevent thromboembolic disease while fibrinolytic drugs can be used to destroy thrombi already formed and can be life saving after a myocardial infarction or stroke. 

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