Patients maintained on warfarin may occasionally need to stop anticoagulant therapy during invasive procedures. Generally, this is accomplished by initiating therapy with unfractionated heparin (high-dose subcutaneous or intravenous heparin) once the International Normalized Ratio (INR) becomes subtherapeutic. Both forms of heparin require monitoring and adjustments to reach a therapeutic level. Intravenous heparin is usually given in the hospital, which adds to the expense. Another approach is to lower the dosage of warfarin or add a small dose of vitamin K to reduce the INR to approximately 1.5 before the procedure. The latter method may carry an increased risk of bleeding, or the addition of vitamin K may lead to temporary warfarin resistance. A final option is to withhold warfarin and not replace it with any anticoagulant therapy until the postoperative period. This method may carry increased risk for thrombosis.
Spandorfer and associates enrolled adults in the study who were receiving chronic anticoagulation therapy for mechanical heart valves, atrial fibrillation and risk factors for stroke, deep venous thrombosis within the past month or known hypercoagulable state with a history of life-threatening thrombosis. Patients were required to have undergone major surgery or an invasive procedure that was considered to be of moderate or high bleeding risk and therefore had to discontinue warfarin therapy. Exclusion criteria included obesity, renal insufficiency, unexplained bleeding in the past year, history of heparin-induced thrombocytopenia and positive heparin antibodies, recent neurosurgery and known pregnancy. Warfarin therapy was discontinued in all patients five to six days before the procedure, depending on the INR. Patients or caretakers received instruction about subcutaneous injections, and enoxaparin, a low-molecular-weight heparin, was started at a dosage of 1 mg per kg every 12 hours approximately 36 hours after warfarin therapy was discontinued. Enoxaparin was withheld 12 to 18 hours before the procedure and restarted at the same dosage level and frequency after the procedure, once hemostasis was achieved. The patient's usual dosage of warfarin was restarted after the procedure, and enoxaparin was discontinued once the INR reached therapeutic levels. Patients received anticoagulation therapy on an outpatient basis unless hospitalization was required.
Of the 20 participating patients, none developed bleeding or thrombotic complications during the procedure. Three patients developed postprocedure soft tissue bleeding complications. Fourteen patients reported little or no difficulty injecting themselves with enoxaparin twice daily. Sixteen patients stated a preference for home anticoagulation regulation rather than hospitalization for intravenous heparin therapy.
The authors conclude that enoxaparin, like other low-molecular-weight heparins, can be given subcutaneously and has a predictable anticoagulation effect that obviates the need for monitoring. The dosage of enoxaparin used in this study was high and may be most beneficial in patients undergoing a procedure that has relatively lower risk of bleeding (e.g., colonoscopy or oral surgery). A lower dosage of enoxaparin may be appropriate in patients having more risky surgery. Further studies are needed to compare different regimens of enoxaparin in different settings and to evaluate the benefit of reduced hospitalization.