Recommendation 1: Low-molecular-weight heparin (LMWH) rather than unfractionated heparin should be used whenever possible for the initial inpatient treatment of deep venous thrombosis (DVT). Either unfractionated heparin or LMWH is appropriate for the initial treatment of pulmonary embolism.
Consistent evidence demonstrates that LMWH is superior to unfractionated heparin for the initial treatment of DVT, particularly for reducing mortality and reducing the risk for major bleeding during initial therapy. Additional trials are needed to more rigorously examine the efficacy of LMWH for the initial treatment of pulmonary embolism, but systematic reviews of existing trials indicate that LMWH is at least as effective as unfractionated heparin for these patients as well. In addition, trials of unfractionated heparin in pulmonary embolism show that many patients are subtherapeutic or supratherapeutic while receiving unfractionated heparin whereas LMWH is quickly and consistently therapeutic, an important consideration in the treatment of VTE.
Recommendation 2: Outpatient treatment of DVT, and possibly pulmonary embolism, with LMWH is safe and cost-effective for carefully selected patients, and should be considered if the required support services are in place.
In trials that compared inpatient and outpatient treatment, the rates of recurrent DVT, major bleeding, and death during follow-up differed only slightly. These studies were conducted among highly selected groups of patients and in clinical systems with the required support services in place. Several studies allowed a brief inpatient admission for stabilization of the patients before randomization to the outpatient group. While some studies enrolled patients with concomitant pulmonary embolism, the majority excluded such patients. Inclusion criteria were strict; most studies excluded patients with previous VTE, thrombophilic conditions, significant comorbid illnesses, pregnant patients, and those unlikely to adhere to outpatient therapy. Therefore, this recommendation cannot be generalized.
Recommendation 3: Compression stockings should be used routinely to prevent postthrombotic syndrome, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis.
The evidence demonstrated a marked reduction in the incidence and severity of postthrombotic syndrome among patients wearing compression stockings, either over-the-counter stockings or custom-fit stockings, if use was initiated within 1 month diagnosis of proximal DVT. Most diagnoses of postthrombotic syndrome occurred early, within the first 2 years after DVT.
Recommendation 4: There is insufficient evidence to make specific recommendations for types of anticoagulation management of VTE in pregnant women.
During pregnancy, women have a 5-fold increased risk for VTE compared with nonpregnant women. Clinicians should avoid vitamin K antagonists in pregnant women because these drugs cross the placenta and are associated with embryopathy between 6 and 12 weeks' gestation, as well as fetal bleeding (including intracranial hemorrhage) at delivery. Neither LMWH nor unfractionated heparin crosses the placenta, and neither is associated with embryopathy or fetal bleeding.
Recommendation 5: Anticoagulation should be maintained for 3 to 6 months for VTE secondary to transient risk factors, and for more than 12 months for recurrent VTE. While the appropriate duration of anticoagulation for idiopathic or recurrent VTE is not definitively known, there is evidence of substantial benefit for extended-duration therapy.
For VTE secondary to transient risk factors, 3 or 6 months of treatment was associated with similar risks for recurrent VTE. In the single study that exclusively enrolled patients presenting with a second episode of VTE, extended-duration (>12 months or indefinite) anticoagulant therapy was associated with fewer recurrences than was termination after 6 months of therapy. For patients with idiopathic VTE (including those with recurrent VTE), extended-duration therapy decreased the relative risk for recurrence by 64% to 95%. Length of therapy in the trials varied widely, from greater than 3 months to 12 months to up to 4 years. The results for extended-duration therapy reflect follow-up only to 4 years; the risk–benefit ratio is not known for longer durations. Clinicians should weigh the benefits, harms, and patient preferences in deciding on the duration of anticoagulation.
Recommendation 6: LMWH is safe and efficacious for the long-term treatment of VTE in selected patients (and may be preferable for patients with cancer).
Evidence from high-quality randomized trials supports the use of LMWH as comparable to oral anticoagulation for VTE in selected patients. Low-molecular-weight heparin may be a useful treatment for patients in whom control of the international normalized ratio (INR) is difficult, and may be more efficacious than oral anticoagulants in patients with cancer.
