Management of Oral Anticoagulant Treatment in Patients with Venous Thromboembolism

ABSTRACT

Oral anticoagulants (OAs) are the drugs of choice for the prevention of recurrence and death in patients with venous thromboembolism (VTE). Oral anticoagulant treatment (OAT) aims to retard blood coagulation to obtain maximum protection against thromboembolic events with the lowest risk of bleeding. The intensity of OAT is ascertained by measuring the prothrombin time (PT), which is expressed as the international normalized ratio (INR). The efficacy and safety of these drugs depends on the ability to maintain the level of anticoagulation as close as possible to the therapeutic target (INR = 2.5) or inside the therapeutic range (INR = 2.0 to 3.0). Given that dosage of oral anticoagulants varies from patient to patient and within the single patient, clinical and laboratory (biological effect of the drug) check-ups must be performed periodically. The management of patients with VTE, as well as that of other patients receiving OAT, includes medical controls and expertise that are better available in specialized centers (anticoagulation clinics).

Venous thromboembolism - oral anticoagulants - warfarin - management - laboratory control

REFERENCES

• 1 Suttie J W. Vitamin K antagonists. In: Colman RW, Hirsh J, Marder VJ, Salzman EW Hemostasis and Thrombosis. Philadelphia, PA; Lippincott 1994: 1565
• 2 Thijssen HHW, Hamulyàk K, Willigers H. 4-Hydroxycoumarin oral anticoagulants: pharmacokinetics-response relationships.  Thromb Haemost. 1988;  60 35-38
• 3 Hull R D, Delmore T, Genton E et al.. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis.  N Engl J Med. 1979;  302 855-858
• 4 Hull R, Delmore T, Carter C et al.. Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis.  N Engl J Med. 1982;  306 189-194
• 5 Caprini J A, Arcelus J I, Reyna J J et al.. Deep vein thrombosis outcome and the level of oral anticoagulation therapy.  J Vasc Surg. 1999;  30 805-811
• 6 Ridker P M, Goldhaber S Z, Danielson E PREVENT Investigators et al.. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.  N Engl J Med. 2003;  348 1425-1434
• 7 Kearon C, Ginsberg J S, Kovacs M J et al.. Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators . . Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.  N Engl J Med. 2003;  349 631-639
• 8 Streiff M B. Vena caval filters: a comprehensive review.  Blood. 2000;  95 3669-3677
• 9 Palareti G, Legnani C, Lee A et al.. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy.  Thromb Haemost. 2000;  84 805-810
• 10 Harrison L, Johnston M, Massicotte M P, Crowther M, Moffat K, Hirsh J. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy.  Ann Intern Med. 1997;  126 133-136
• 11 Tait R C, Sefcick A. A warfarin induction regimen for out-patient anticoagulation in patients atrial fibrillation.  Br J Haematol. 1998;  101 450-454
• 12 Barcellona D, Vannini M L, Fenu L, Balestrieri C, Marongiu F. Warfarin or acenocoumarol: which is better in the management of oral anticoagulants?.  Thromb Haemost. 1998;  80 899-902
• 13 Gallus A, Jackaman J, Tillet J, Mills W, Wycherley A. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism.  Lancet. 1986;  ii 1293-1296
• 14 Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 1: heparin.  Circulation. 1994;  89 1449-1468
• 15 Hull R D, Raskob G E, Rosenbloom E et al.. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.  N Engl J Med. 1990;  322 1260-1264
• 16 Hyers T M, Agnelli G, Hull R D et al.. Antithrombotic therapy for venous thromboembolic disease.  Chest. 2001;  119 176S-193S
• 17 Pengo V, Banzato A, Garelli E, Zasso A, Biasiolo A. Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin Kl) compared with warfarin discontinuation.  Blood Coagul Fibrinolysis. 1993;  4 739-741
• 18 Crowther M A, Julian J, McCarty D et al.. Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial.  Lancet. 2000;  356 1551-1553
• 19 Panneerselvam S, Baglin C, Lefort W, Baglin T. Analysis of risk factors for over-anticoagulation in patients receiving long-term warfarin.  Br J Haematol. 1998;  103 422-424
• 20 Palareti G, Legnani C, Guazzaloca G Ad hoc Study Group of the Italian Federation of Anticoagulation Clinics et al.. Risk factors for highly unstable response to oral anticoagulation: a case-control study.  Br J Haematol. 2005;  129 72-78
• 21 Wells P S, Holbrook A M, Crowther N R, Hirsh J. Interaction of warfarin with drugs and food.  Ann Intern Med. 1994;  121 676-683
• 22 Pemgo V, Finazzi G, Testa S, Tripodi A. on behalf of the Italian Federation of Anticoagulation Clinics . Self-testing and self-monitoring of oral anticoagulant therapy: consensus of the Italian Federation of Anticoagulation Clinics.  Haematologica. 2003;  88(suppl 3) 1-10