There are 600,000 cases of venous throm-boembolism (VTE) in the United States every year. Of all persons with undetected or untreated pulmonary embolism, 26 percent will have a fatal embolic event, and another 26 percent will have a recurrent embolic event that could become fatal. Therefore, an early diagnosis of VTE is important to prevent mortality and morbidity in this population.

Diagnosis

CLINICAL PREDICTION RULES

The current evidence supports using a clinical prediction rule to establish the pretest probability of VTE. Physicians should use the Wells prediction rule to estimate the probability of deep venous thrombosis (DVT; Table 1) and pulmonary embolism (Table 2) before performing and interpreting other diagnostic testing. However, the Wells prediction rule performs best in younger patients without comorbidities or a history of VTE.

Patients with low pretest probability of the disease and a negative d-dimer assay have a very low likelihood of VTE that reduces the need for further imaging.

d-DIMER ASSAY

Enzyme-linked immunosorbent assay (ELISA), quantitative rapid ELISA, and advanced turbidimetric d-dimer determinations are highly sensitive tests helpful in the diagnosis of VTE. A negative highly sensitive d-dimer test largely excludes the diagnosis of proximal DVT and pulmonary embolism in younger patients whose symptoms are of short duration and whose pretest probability of VTE is low, based on the Wells prediction rule. In older patients, those with associated comorbidities, and those with a long duration of symptoms, a d-dimer assay alone may not be sufficient to rule out VTE, even in an otherwise low-risk patient.

The sensitivity of d-dimer assays varies, so physicians should be informed of the type of d-dimer assay being used.

ULTRASONOGRAPHY

For patients who are symptomatic, there is strong evidence that ultrasonography has a high specificity and sensitivity for diagnosing proximal DVT of the lower extremities. Sensitivity, however, is decreased in patients who have DVT in the calf or who are asymptomatic, so negative ultrasonography cannot rule out DVT in these patients. Therefore, ultrasonography is recommended for patients who are at intermediate or high risk of DVT according to the Wells prediction rule.

Ultrasonography or venography should be repeated in patients with suspected calf–vein DVT whose ultrasonography results are negative, as well as in patients with suspected proximal DVT but whose ultrasonography results are inadequate or equivocal. Therefore, contrast venography should still be considered the definitive test to rule out DVT.

HELICAL COMPUTED TOMOGRAPHY

Recent evidence suggests that helical computed tomography (CT) may have higher specificity and sensitivity compared with conventional pulmonary arteriography for the diagnosis of pulmonary embolism, and it is likely that technology will improve the accuracy of CT in the future. However, in patients who have a high pretest probability of pulmonary embolism and a negative CT scan, further imaging studies (e.g., ventilation-perfusion scan, multidetector helical computed axial tomography) are needed. For those patients, evidence suggests that CT alone may not be sensitive enough to exclude pulmonary embolism. Therefore, a single or sequential ultrasonography assessment of the lower extremities or pulmonary angiography may be warranted.

Management of VTE

INPATIENT TREATMENT

Low-molecular-weight heparin (LMWH) is superior to unfractionated heparin for the initial treatment of DVT because it reduces mortality rates and the risk of major bleeding during initial therapy. Therefore, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommend that LMWH be used for the initial inpatient treatment of DVT. Unfractionated heparin or LMWH is appropriate for the initial treatment of patients with pulmonary embolism.

OUTPATIENT TREATMENT

In stable patients for whom the required support services are in place, outpatient treatment of VTE with LMWH is as safe as inpatient treatment and is cost-effective.

PREVENTION OF POST-THROMBOTIC SYNDROME

There is a marked reduction in the severity and incidence of post-thrombotic syndrome among patients who wear over-the-counter or custom-fit compression stockings if their use is initiated within one month of the diagnosis of proximal DVT. Therefore, compression stockings should be routinely used within one month of proximal DVT diagnosis; use should be continued for at least one year to prevent post-thrombotic syndrome in these patients.

TREATMENT DURING PREGNANCY

Pregnant women have a fivefold increased risk of VTE compared with women who are not pregnant. Vitamin K antagonists should be avoided in pregnant women because they can cross the placenta, and they are associated with embryopathy between six and 12 weeks' gestation and fetal bleeding at delivery. Although there is no association between embryopathy or fetal bleeding and the use of LMWH or unfractionated heparin, there is not enough evidence to make recommendations for anticoagulation treatment in pregnant patients with VTE.

ANTICOAGULATION THERAPY

The ACP and AAFP recommend that anticoagulation therapy be maintained for three to six months in patients with VTE secondary to transient risk factors. For patients with recurrent VTE, anticoagulation therapy should be continued for more than 12 months. The exact duration of anticoagulation therapy is not fully understood in patients with idiopathic or recurrent VTE, but extended-duration therapy can provide substantial benefit to these patients. Physicians should weigh the harms, benefits, and patient preferences when deciding the duration of anticoagulation therapy.

LONG-TERM MANAGEMENT OF VTE

LMWH is comparable with oral anticoagulation therapy in select patients with VTE, and it may be useful in treating patients whose International Normalized Ratio is difficult to control. Therefore, the ACP and the AAFP recommend the use of LMWH as a safe and effective therapy for the long-term treatment of VTE. In addition, LMWH may be more effective than oral anticoagulation therapy in patients with cancer.