Venous thromboembolism: What to do after anticoagulation is started
ABSTRACTAfter anticoagulation has been started in patients with venous thromboembolism (VTE), three issues need to be addressed: the length of therapy, measures to help prevent postthrombotic syndrome, and a basic workup for malignancy in patients with idiopathic VTE.
KEY POINTS
- A low-molecular-weight heparin for at least 6 months is the treatment of choice for cancer-related VTE.
- We recommend 3 months of anticoagulation for VTE caused by a reversible risk factor and indefinite treatment for idiopathic VTE in patients without risk factors for bleeding who can get anticoagulation monitoring.
- Clinical factors are more important in deciding the duration of anticoagulation therapy than evidence of an inherited thrombophilic state.
- Elastic compression stockings reduce the risk of postthrombotic syndrome substantially.
- Patients with idiopathic VTE should have a basic screening for malignancy.
Recommendation: At least 3 months of warfarin or equivalent
We agree with the ACCP recommendation2 that patients with unprovoked VTE should receive at least 3 months of anticoagulation with a vitamin K antagonist.
If the patient has no risk factors for bleeding and good anticoagulant monitoring is achievable, we agree with long-term anticoagulation for proximal unprovoked deep vein thrombosis or pulmonary embolism, and 3 months of therapy for isolated distal unprovoked deep vein thrombosis.
Patient preferences and the risk of recurrence vs the risk of bleeding should be discussed with patients when contemplating indefinite anticoagulation.
If testing is being considered to assist in the decision to prescribe indefinite anticoagulation, we prefer using d-dimer levels rather than ultrasonography to detect residual venous thrombosis because of its ease of use and the strength of the current evidence.
PREVENTING POSTTHROMBOTIC SYNDROME
The postthrombotic (postphlebitic) syndrome is a chronic and burdensome consequence of deep vein thrombosis that occurs despite anticoagulation therapy. It is estimated to affect 23% to 60% of patients and typically manifests in the first 2 years.40 It is not only costly in clinical terms, with decreased quality of life for the patient, but health care expenditures have been estimated to range from $400 per year in a Brazilian study to $7,000 per year in a US study.40
Typical symptoms include leg pain, heaviness, swelling, and cramping. In severe cases, chronic venous ulcers can occur and are difficult to treat.41
The definition of postthrombotic syndrome has been unclear over the years, and six different scales that measure signs and symptoms have been reported.42
The Villalta scale has been proposed by the International Society of Thrombosis and Hemostasis as a diagnostic standard to define postthrombotic syndrome.42 This validated scale is based on five clinical symptoms, six clinical signs, and the presence or absence of venous ulcers. Each clinical symptom and sign is scored as mild (1 point), moderate (2 points), or severe (3 points). Symptoms include pain, cramps, heaviness, paresthesia, and pruritus; the six clinical signs are pretibial edema, skin induration, hyperpigmentation, redness, venous ectasia, and pain on calf compression.
According to the International Society of Thrombosis and Hemostasis, postthrombotic syndrome is present if the Villalta score is 5 or greater or if a venous ulcer is present in a leg with previous deep vein thrombosis. Further, using the Villalta scale, postthrombotic syndrome can be categorized as mild (score 5–9), moderate (10–14), or severe (≥ 15).
A limitation of the Villalta scale is that the presence or absence of a venous ulcer has not been assigned a score. Since a venous ulcer requires more aggressive measures, the society defines postthrombotic syndrome as severe if venous ulcers are present.42
Acute symptoms of deep vein thrombosis may take months to resolve and, indeed, acute symptoms may transition to chronic symptoms without a symptom-free interval. It is recommended that postthrombotic syndrome not be diagnosed before 3 months to avoid inappropriately attributing acute symptoms and signs of deep vein thrombosis to the postthrombotic syndrome.42
Studies of stockings
A systematic review of three randomized trials44 concluded that elastic compression stockings reduce the risk of postthrombotic syndrome (any severity) from 43% to 20% and severe postthrombotic syndrome from 15% to 7%.43
The first of these trials44 randomized patients soon after the diagnosis of deep vein thrombosis to receive made-to-order compression stockings that were rated at 30 to 40 mm Hg or to be in a control group that did not receive stockings. The second trial45 randomized patients 1 year after the index event of deep vein thrombosis to receive 20- to 30-mm Hg stockings or stockings that were two sizes too large (the control group). The third study46 randomly allocated patients to receive “off-the-shelf” stockings (30–40 mm Hg) or no stockings. Each study used its own definition of postthrombotic syndrome.
Although these studies strongly suggest compression stockings prevent postthrombotic syndrome, several methodologic issues remain:
- A standard definition of postthrombotic syndrome was not used
- The amount of compression varied between studies
- The studies were not blinded.
Lack of blinding becomes most significant when an outcome is based on subjective findings, like the symptoms that make up a large part of the diagnosis of postthrombotic syndrome.
The SOX trial, currently under way, is designed to address these methodologic issues and should be completed in 2012 (clinicaltrials.gov Identifier: NCT00143598).
Recommendation: Stockings for at least 2 years
We agree with the ACCP recommendation that a patient who has had a symptomatic proximal deep vein thrombosis should wear an elastic compression stocking with an ankle pressure gradient of 30 to 40 mm Hg as soon as possible after starting anticoagulant therapy and continuing for a minimum of 2 years.2
