New recommendations for VTE
The Joint American College of Physicians/American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism recently released new recommendations for treatment and diagnosis of venous thromboembolism (VTE):
Diagnosis
Recommendation 1: Validated clinical prediction rules should be used to estimate pretest probability of VTE, both deep venous thrombosis (DVT) and pulmonary embolism, and for the basis of interpretation of subsequent tests.
Good-quality evidence supports the use of clinical prediction rules to establish pretest probability of disease. The Wells prediction rules for DVT and for pulmonary embolism have been validated and are frequently used to estimate the probability of VTE before performing more definitive testing on patients. The Wells prediction rule performs better in younger patients without comorbidities or a history of VTE than it does in other patients. Physicians should use their clinical judgment in cases where a patient is older or presents with comorbidities.
Recommendation 2: In appropriately selected patients with low pretest probability of DVT or pulmonary embolism, obtaining a high-sensitivity D-dimer is a reasonable option, and if negative indicates a low likelihood of VTE.
In selected patients who have a low pretest probability of VTE as defined by the Well prediction rules, a negative high-sensitivity D-dimer assay for VTE has sufficiently high predictive value to reduce the need for further imaging studies. Currently, enzyme-linked immunosorbent assay (ELISA), quantitative rapid ELISA and advanced turbidimetric D-dimer determinations are highly sensitive assays (sensitivity, 96% to 100%), and their use is practical in diagnosis of VTE. D-Dimer testing has the highest negative predictive value when used to exclude VTE in younger patients without associated comorbidity or history of VTE and with short duration of symptoms, because the Wells criteria more accurately predict a low pretest probability of VTE in such patients. In older patients, those with associated comorbidity and those with long duration of symptoms, a D-dimer alone may not be sufficient to rule out VTE.
Recommendation 3: Ultrasound is recommended for patients with intermediate to high pretest probability of DVT in the lower extremities.
|
For patients who have intermediate or high pretest probability of pulmonary embolism, imaging is essential. |
Use of ultrasound in diagnosing symptomatic thrombosis in the proximal vein of the lower limb is recommended for patients whose pretest probability of disease falls in the category of intermediate to high risk for DVT under the Wells prediction rule. Ultrasound is less sensitive in patients who have DVT limited to the calf; therefore, a negative ultrasound does not rule out DVT in these patients. Repeat ultrasound or venography may be required for patients who have suspected calf-vein DVT and a negative ultrasound and for patients who have suspected proximal DVT and an ultrasound that is technically inadequate or equivocal. Contrast venography is still considered the definitive test to rule out the diagnosis of DVT.
Recommendation 4: Patients with intermediate or high pretest probability of pulmonary embolism require diagnostic imaging studies.
For patients who have intermediate or high pretest probability of pulmonary embolism, imaging is essential. Possible tests include ventilation–perfusion (V/Q) scan, multidetector helical computer axial tomography (CT), and pulmonary angiography. Recent systematic reviews indicate that CT alone may not be sufficiently sensitive to exclude pulmonary embolism in patients who have a high pretest probability of pulmonary embolism.
Treatment
Recommendation 1: Low-molecular-weight heparin (LMWH) rather than unfractionated heparin should be used whenever possible for the initial inpatient treatment of 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, most excluded such patients. Inclusion criteria were strict: Most studies excluded patients with previous VTE, thrombophilic conditions or 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 one month of diagnosis of proximal DVT and continuing for a minimum of one 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 one month of diagnosis of proximal DVT. Most diagnoses of postthrombotic syndrome occurred early, within the first two 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 five-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 six 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 three to six 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.
|
Evidence from high-quality randomized trials supports the use of LMWH as comparable to oral anticoagulation for VTE in selected patients. |
For VTE secondary to transient risk factors, three or six 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 six 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 three months to 12 months to up to four years. The results for extended-duration therapy reflect follow-up only to four 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 is difficult and may be more efficacious than oral anticoagulants in patients with cancer.
The complete recommendations and the accompanying background reviews appeared in the March 20 and Feb. 6, 2007, issues of Annals of Internal Medicine, respectively, and are available at www.annals.org.
More from ACP Press
IM Essentials for Clerkship Students 2: Augment your learning with ACP's authoritative text and online supplemental resources.
Internal Medicine 2009
April 23-25, 2009 in Philadelphia
Attention Lab Owners:
Get Live Answers at a Price You Can Afford
MLE offers ACP members superior service, affordability, online options and other special features.