Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 28-year-old man is evaluated 24 hours after a new diagnosis of a left calf deep venous thrombosis. One week ago, he underwent orthopedic surgery. Two weeks ago, he returned from vacationing in Italy on an 8-hour flight. Current medications are enoxaparin, 80 mg subcutaneously twice daily, and warfarin, 5 mg/d.
On physical examination, temperature is normal, blood pressure is 145/85 mm Hg, pulse rate is 72/min, and respiration rate is 18/min. BMI is 25. His lungs are clear. His left calf is erythematous and edematous.
Duplex ultrasound obtained yesterday confirms a left posterior tibial vein thrombosis. Laboratory results from his emergency department visit reveal factor V Leiden heterozygosity.
The patient asks why he developed this blood clot and how long he will have to take warfarin.
Which of the following is the most appropriate management of this patient’s venous thromboembolism?
A: Low-intensity warfarin (INR, 1.5-2) for at least 3 months
B: Standard-intensity warfarin (INR, 2-3) for at least 12 months
C: Standard-intensity warfarin (INR, 2-3) for at least 3 months
D: Standard-intensity warfarin (INR, 2-3) for life
MKSAP Answer and Critique
The correct answer is C: Standard-intensity warfarin (INR, 2-3) for at least 3 months. This item is available to MKSAP 16 subscribers as item 12 in the Hematology/Oncology section.
Standard-intensity warfarin (INR, 2 to 3) for at least 3 months is the most appropriate management of this patient with a triggered episode of venous thromboembolism (VTE). Although distal (calf vein) deep venous thrombosis (DVT) is associated with a low risk for pulmonary embolism, these thrombi confer a substantial risk for progression into the proximal deep venous system in the absence of anticoagulation. In one randomized study, 29% of patients treated with a 5-day course of unfractionated heparin alone developed recurrent VTE compared with none in the group receiving warfarin for 3 months.
This patient has several identifiable risk factors for VTE: recent major orthopedic surgery, recent travel, and factor V Leiden heterozygosity. Major inpatient surgery is associated with a 70-fold increased risk for VTE; ambulatory surgery is associated with a 10-fold increased risk. The risk associated with surgery is greatest in the first few weeks after surgery and declines thereafter, reaching baseline as long as 12 months later. Therefore, this patient’s recent orthopedic surgery played a major role in the pathogenesis of his calf vein DVT. In comparison, travel is associated with a modest twofold increased risk for VTE, and factor V Leiden is associated with a fivefold increased risk of VTE. Although factor V Leiden is associated with a significant risk for initial VTE, it is not associated with a significant risk for recurrent VTE (1.5-fold). Consequently, the presence of factor V Leiden in this patient does not mandate prolonged therapy.
Low-intensity warfarin (INR, 1.5-2) for 3 months would not be the optimal choice for this patient’s triggered episode of calf vein DVT. Low-intensity warfarin therapy was found to be inferior to standard-intensity warfarin therapy (INR, 2-3) for treatment of patients with idiopathic VTE. Low-intensity therapy was initiated after at least 3 months of standard-intensity therapy (INR, 2-3). Low-intensity warfarin therapy has never been tested for the initial 3 months of VTE treatment.
Lifelong warfarin (INR, 2-3) is not the best management approach for this patient with a triggered episode of VTE. The bleeding risks of long-term warfarin (at least 1% to 2% per year) outweigh the risk of recurrence (0.7% per year).
- Standard-intensity warfarin for at least 3 months is the most appropriate management for patients with risk factors for venous thromboembolism.
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