Physical examination
• Homans' test: Dorsiflexion of foot elicits pain in posterior calf. Warning: it must be noted that it is of little diagnostic value and is theoretically dangerous because of the possibility of dislodgement of loose clot.
• Pratt's sign: Squeezing of posterior calf elicits pain.
D-dimer testing
• The D-dimer test has an important role in the diagnostic approach to deep venous thrombosis (DVT). D-dimer fibrin fragments are present in fresh fibrin clot and in fibrin degradation products of cross-linked fibrin. Monoclonal antibodies specific for the D-dimer fragment are used to differentiate fibrin-specific clot from non–cross-linked fibrin and from fibrinogen. These specific attributes of the D-dimer antibodies account for their high sensitivity for venous thromboembolism.
• D-dimer level may be elevated in any medical condition where clots form. D-dimer level is elevated in trauma, recent surgery, hemorrhage, cancer, and sepsis. Many of these conditions are associated with higher risk for DVT. The D-dimer assays have low specificity for DVT; therefore, they should only be used to rule out DVT, not to confirm the diagnosis of DVT.
• D-dimer levels remain elevated in DVT for about 7 days. Patients presenting late in the course, after clot organization and adherence have occurred, may have low levels of D-dimer. Similarly, patients with isolated calf vein DVT may have a small clot burden and low levels of D-dimer that are below the analytic cut-off value of the assay. This accounts for the reduced sensitivity of the D-dimer assay in the setting of confirmed DVT.
• Many different D-dimer assays are available, with varying sensitivities and specificities. The assays are not standardized. They incorporate different monoclonal antibodies to the D-dimer fragment. Results may be reported quantitatively or qualitatively. Different units may be used; some assay results are reported as fibrinogen equivalent units (FEU) and others in nanograms per milliliter (ng/mL). The results of one assay cannot be extrapolated to another.
• Most studies have confirmed the clinical utility of D-dimer testing, and most clinical algorithms incorporate their use. Physicians should know their hospital's D-dimer assay.
• All D-dimer assays have been evaluated in various validation studies that determine the assay's sensitivity, specificity, and negative predictive value (NPV). Unfortunately, fewer management studies have been conducted to determine the safety of withholding anticoagulant therapy on the basis of a negative test result. Furthermore, the NPV of a specific assay falls as the pretest probability of the study population at risk for DVT increases. An assay with a sensitivity of 80% has an NPV of 97.6% in a low-risk patient. However, the NPV of the same assay is only 33% in high-risk patients with a pretest probability of 90% for DVT.
• Traditional enzyme-linked immunosorbent assays (ELISAs), although accurate, are time-consuming and not practical for use in the ED. A rapid ELISA assay (VIDAS) with high sensitivity was validated in a large European trial. In that study a negative VIDAS D-dimer assay essentially ruled out DVT. All patients with a negative D-dimer result did not require further diagnostic testing with ultrasonography.
• The older qualitative latex agglutination assay is not accurate and should not be used for making treatment decisions in patients with suspected DVT. Newer latex-enhanced immunoturbidimetric and immunofiltration assays have high sensitivity and are available.
• A rapid qualitative RBC agglutination assay (SimpliRED) is available. It is sensitive for proximal vein DVT but less so for calf vein DVT. A large study confirmed that, in low-risk patients with low pretest probability for DVT, a negative SimpliRED D-dimer result rules out DVT. Ultrasonography was not required in these patients.
• Current evidence strongly supports the use of a D-dimer assay in the clinical algorithm of suspected DVT. A negative D-dimer assay result rules out DVT in patients with low-to-moderate risk (Wells DVT score <2). A negative result also obviates surveillance and serial testing in patients with moderate-to-high risk and negative ultrasonographic findings.
Results
• A negative D-dimer assay result rules out DVT in patients with low-to-moderate risk and a Wells DVT score less than 2.
• All patients with a positive D-dimer assay result and all patients with a moderate-to-high risk of DVT (Wells DVT score >2) require a diagnostic study (duplex ultrasonography).
Other blood tests
• Protein S, protein C, antithrombin III, factor V Leiden, prothrombin 20210A mutation, antiphospholipid antibodies, and homocysteine levels can be measured.
• Deficiencies of these factors or the presence of these abnormalities all produce a hypercoagulable state. These are rare causes of DVT.
• Laboratory investigations for these abnormalities are primarily indicated when DVT is diagnosed in patients younger than 50 years, when there is a confirmed family history of a hypercoagulable state or a familial deficiency, when venous thrombosis is detected in unusual sites, and in the clinical setting of warfarin-induced skin necrosis.
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