Owing to the poor accuracy of clinical methods in identifying DVT, all patients with any signs or symptoms suggesting DVT must undergo an objective diagnostic evaluation. Less than one-third of patients with clinically suspected DVT are found to have the disease following objective investigation. 4 Several investigative techniques are available to search for a deep thrombus, including plasma D-dimer level, impedance plethysmography (IPG), Doppler ultrasound (duplex), contrast venography, radionuclide scintigraphy, and magnetic resonance imaging (MRI).

Venography has represented the historical "gold standard" for the detection of DVT. It can be useful for patients with a high clinical probability of DVT when noninvasive tests are negative. However, it is an invasive, often painful, and expensive test that may cause contrast-related reactions or iatrogenic venous thrombus in about 1 to 2 percent of patients. It is difficult to perform and requires considerable expertise. When contrast is seen throughout the deep venous system (not possible in 5 to 10 percent of tests), a venogram reliably excludes DVT. Inadequate visualization of the deep venous system can occur due to difficulties with venous access (e.g., obesity, severe edema, cellulitis), dilution of contrast in the proximal lower limb, or a previous thrombus.

The commonest test used to identify a DVT in North America is ultrasonography. B-mode ultrasound gives two-dimensional images of a vein and its surrounding structures and can directly visualize a clot, while Doppler flow capacity when combined with color images provides a visual and audible evaluation of blood flow for venous obstruction. B-mode ultrasonography combined with Doppler flow is termed a duplex. A duplex scan with or without color flow is highly sensitive and specific for a proximal DVT (clot proximal to the popliteal veins). The positive predictive value of ultrasound is higher than IPG for DVTs (94 versus 83 percent, respectively). Both of these tests are portable, noninvasive, safe, quick, readily accessible, accurate for proximal DVTs, and provide immediate information. Ultrasound testing requires more expertise (due to subjective interpretation). It is also more expensive than an IPG but is the test of choice when available owing to its higher accuracy. Both tests are insensitive for calf DVTs and serial testing is required to exclude the extension of clot to proximal veins. Some centers will not routinely scan the leg for a calf DVTs, choosing instead to do a more time-limited study looking only for the more significant proximal clots.

All plethysmographs measure a change in volume. An IPG that can be done at the bedside measures changes in electrical resistance in response to changes in calf volume secondary to venous obstruction. The procedure involves a supine patient with a leg externally rotated and knee partially flexed, having an 8-in. pneumatic cuff placed around the thigh and inflated to 37 to 51 mmHg to preferentially obstruct venous return, causing calf enlargement. Measurements are made with two electrodes on the calf after cuff inflation and then rapid deflation within 3 s of cuff release. Measurements are plotted on a graph and, if they lie above an experimentally determined baseline, the test is negative for a DVT. If the measurements lie below this line, the test is repeated, with increasing periods of cuff inflation (45 to 120 s). If several of these repeat measurements lie below the baseline, the test is considered positive for DVT. Several studies have shown that sensitivity and specificity for proximal DVT are about 95 percent.5 False positives can occur with PPS, abdominal or pelvic neoplasms, CHF, and pregnancy. Plethysmography is insufficiently accurate to be useful for isolated calf DVT.

Several radioisotope techniques are available for investigating for DVT, including 111In- or 99mTc-labeled antifibrin monoclonal antibodies, 125I-labeled fibrinogen, and 99mTc-labeled red blood cells or macroaggregated albumin. These radioisotopes may be incorporated into actively forming thrombus and can be detected by scanning the extremity hours or days after injection. There are several disadvantages to radionuclide venography which make it a suboptimal test for detecting a DVT. While sensitivity for detecting calf DVT is about 90 percent, sensitivity for thigh DVT is as low as 60 percent and even lower for pelvic veins. 5 Still, this test has been used to complement a negative or equivocal ultrasound exam in high risk patients such as those who have undergone surgery or have an indeterminate lung scan for PE. Radionuclide venography is expensive, time-consuming and not as accurate as IPG or a duplex for proximal DVTs.

Some authorities advocate MRI as the "gold standard" for imaging the venous system. It is at least as accurate as any other investigational modality and can detect a filling defect in the entire extremity (including calf veins) and pelvic veins, which are sometimes not well visualized by ultrasonography or venography. An MRI visualizes both extremities simultaneously and can identify alternative causes of extremity swelling such as cysts, aneurysms, hematomas, tumors, and other masses. Some of the limitations of MRI include its cost, lack of ready availability, lack of portability, and inability to be used in patients harboring ferromagnetic objects (prostheses, pacemakers).

D-dimer fragments can be measured as an indicator of the presence or absence of DVT or PE. A quantitative enzyme-linked immunosorbent assay (ELISA) D-dimer level less than 250 ng/mL is helpful to exclude a venous thrombosis, but the test takes several hours to perform (latex and immunofiltration techniques are quicker but less sensitive). It is a fairly nonspecific test, as many other conditions such as infections, surgery, trauma, cardiovascular disease, and cancer can elevate a D-dimer level. It follows, then, that despite a sensitivity of over 80 to 90 percent, a D-dimer level is useful only when it is low.5 The combination of a normal IPG or ultrasound and a low D-dimer level has a negative predictive value of about 99 percent for proximal DVT.4

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