What is the most appropriate therapy for a patient with a calf deep venous thrombosis (DVT)?
Patients with a first episode of calf DVT with a transient risk factor should receive heparin therapy followed by oral anticoagulation for six to 12 weeks. [Strength of recommendation: A, based on systematic review of randomized controlled trials (RCTs)] If anticoagulation is contraindicated, physicians should monitor for proximal thrombus extension with duplex ultrasound twice weekly for two weeks. [Strength of recommendation: C, based on consensus guideline] The use of low-molecular-weight heparin (LMWH), outpatient therapy, compression stockings, elevation of the extremity, and early mobilization may be beneficial based on extrapolation from studies of proximal DVT.
A systematic review1 of the treatment of DVT conducted by the Agency for Health-care Research and Quality (AHRQ) concluded that anticoagulation is beneficial for symptomatic calf DVT, based primarily on two studies of isolated calf thromboses. One RCT2 of 51 adults with calf DVT demonstrated that three months of warfarin treatment (International Normalized Ratio [INR] 2.5 to 4.2) significantly reduced the likelihood of recurrence, extension, and pulmonary embolism at three months (29 versus zero percent, number needed to treat [NNT]: 4) and one year (32 versus 4 percent, NNT: 4) compared to initial heparin followed by compression stockings alone. Another RCT3 compared six weeks of oral anticoagulation to 12 weeks of oral anticoagulation (INR 2 to 3) in 197 adults with a first episode of calf DVT. They found no statistically significant difference in recurrence rates (2 to 3 percent, respectively) or bleeding (13 to 22 percent, respectively) during 15 months of follow-up. All patients also received compression stockings and initial unfractionated heparin or LMWH therapy.
Further recommendations for treating calf DVT come from studies of proximal DVT. Based on 14 systematic reviews comparing LMWH to unfractionated heparin for initial treatment of any DVT (some with pulmonary emboli), the AHRQ review1 concluded that LMWH reduced the rate of thrombus extension, DVT recurrence, major bleeding, and death. However, reviews since 1998 report smaller magnitudes of benefit than older reviews.1 A Cochrane systematic review4 was updated in August, 2004, and came to similar conclusions.
A 2001 Cochrane systematic review5 found limited evidence (three RCTs that excluded many patients and had other methodological flaws) that outpatient management of proximal DVT with unfractionated heparin or LMWH in selected patients did not increase complications. They noted that LMWH is likely to become common practice because of patient preference and cost savings.5
Another Cochrane systematic review6 of proximal DVT found that graduated elastic compression stockings (20 to 40 mm Hg at the ankle) significantly reduced the likelihood of post-thrombotic syndrome two years later (NNT: 4; 95 percent confidence interval, 3 to 6).6 This syndrome of chronic leg discomfort, edema, and skin changes affects one third of patients with DVT within five years.6
Recommendations from Others
In the Seventh Conference on Antithrombotic and Thrombolytic Therapy, the American College of Chest Physicians (ACCP) recommends treating symptomatic isolated calf DVT with anticoagulation for three months (INR 2 to 3).7 They explicitly place higher value on “preventing recurrent thromboembolic events…[than] on bleeding and cost.”7
The Institute for Clinical Systems Improvement (ICSI) notes: “Increasing evidence suggests that patients with symptomatic calf DVT benefit from treatment similar to that for proximal DVT,” but does not recommend specific durations of anticoagulation for calf DVT.8 If a patient with calf DVT has contraindications to anticoagulation, they state that: “serial ultrasound (e.g., at 3 and 7 days) may be useful to evaluate for propagation of thromboses,” which typically occurs in the first week or two after diagnosis.8
Without long-term anticoagulation (six to 12 weeks), patients with uncomplicated calf DVT have a 20 percent risk of clot propagation into proximal DVT,8 a 30 percent risk of recurrence,1–8 and a 20 percent or greater risk of developing post-thrombotic syndrome.1,7 Oral anticoagulation for DVT carries a steady 2 percent annual risk of major hemorrhage plus risk of minor hemorrhage.1 It is appropriate to consider longer durations of anticoagulation for recurrent DVT, prothrombotic genotype or permanent risk factors, cancer, and idiopathic calf DVT. For these patients, clinicians must extrapolate from the AHRQ, ICSI, and ACCP recommendations for risk stratification and treatment duration, which are based on proximal DVT studies.