Both deep vein thrombosis (DVT) and pulmonary …



D-dimer as an Element of Clinical Algorithms for the Evaluation of Deep Vein Thrombosis and Pulmonary Embolus in the Emergency Room Setting

Pathologist Summary

Both deep vein thrombosis (DVT) and pulmonary embolus (PE) are difficult to diagnose in the emergency room setting. These are a common diagnosis often not made in life but found at autopsy. Diagnosis has depended upon a clinical impression that is confirmed by diagnostic imaging modalities that have poor sensitivity and specificity.

• For diagnosis of DVT the two primary diagnostic imaging modalities are impedance plethysmography (IPM) and compression ultrasound of the calf (CUS). Both modalities have low sensitivity to detect DVT. A negative test result requires repeat testing to assure that a thrombus is not present and if present, hasn’t enlarged and propagated.

• The diagnosis of PE is often confirmed with a lung scan (LS). LS are often difficult to interpret because of underlying pulmonary pathology. LS also have poor sensitivity. The gold standard to detect PE is the pulmonary arteriogram (PA); this has high sensitivity and specificity. The drawbacks of PA are that they are expensive, time consuming, and require a high level of expertise.

The clinical laboratory can serve an important role in the evaluation of DVT and PE. The most useful laboratory test is D-dimer when used in conjunction with imaging modalities. Appropriate use of D-dimer as part of evaluation algorithms reduces the need for PA and allows diagnoses of DVT and PE to be excluded with greater confidence. This improves utilization of resources, assures patients receive appropriate therapy, and allows many patients to be discharged earlier with less invasive diagnostic tests.

D-dimer has been used as an indication of fibrinolysis. During clot formation, fibrin monomers polymerize and form cross-links between the D loci of two strands of fibrin thus forming a D-dimer. When fibrinolysis occurs, these D-dimers are released from the clot as a soluble form in circulation. The circulating D-dimer is assayed with antibody-based assays. The test does not measure thrombotic activity. Rather, the test measures a byproduct of thrombolytic activity.

Four common methods are available to measure D-dimer.

1. Microtiter plates require time consuming setup and long incubation. Whereas this method is useful in analyzing batches of specimens it is not effective in the emergency room setting.

2. The traditional rapid latex test (qualitative) has been available for many years. It is useful to measure D-dimer in the presence of disseminated intravascular coagulation (DIC). This traditional method lacks sufficient sensitivity and specificity to detect localized thrombotic events such as DVT and PE. A recent modified latex test (quantitative) may have sufficient sensitivity to detect both DVT and PE.

3. The rapid ELISA test requires expensive equipment and can be performed on a stat basis. The test has high sensitivity but relatively low specificity.

4. The red cell agglutination test depends upon visual interpretation of results with no equipment required. Intraobserver interpretation adds variability in the results. Like rapid ELISA tests, this test has high sensitivity but relatively low specificity.

The rapid latex (quantitative), ELISA, and red cell agglutination tests may be positive in specimens of patients with malignancies, infection, and chronic inflammatory conditions, without DVT or PE present. Thus, the D-dimer test is proposed in many algorithms for outpatients only when the incidence of these confounding conditions is low. In the emergency room setting, these tests with a high sensitivity have a high negative predictive value. This high negative predictive value is important in discharging patients appropriately.

Several different diagnostic algorithms have been proposed. D-dimer should be used with a clinical algorithm to provide efficient utilization of resources and optimal diagnosis. This presentation includes clinical algorithms based on the level of clinical suspicion for DVT or PE.

• Some algorithms involve D-dimer alone when there is a low clinical suspicion. When D-dimer is negative in a patient for whom the clinical suspicion is low, the patient is often discharged.

• Most diagnostic algorithms involve diagnostic imaging modalities, i.e., LS, USC, or IPM. When the chosen diagnostic imaging and D-dimer tests are both negative, the diagnosis of DVT and PE are generally excluded.

• When either the chosen diagnostic imaging or D-dimer tests are positive, the clinical history must be carefully reviewed to determine what additional studies are appropriate for diagnosis and treatment.

Outcomes can be measured to assure appropriate utilization of resources and patient safety.

In summary, the role of D-dimer in the diagnostic consideration of DVT and PE in the emergency room setting continues to evolve. The use of clinical algorithms is advocated here to achieve the objectives of improving resource utilization and patient management in the emergency room setting. Outcomes can be tracked to assure that imaging modalities and the clinical laboratory are used efficiently to achieve these objectives.

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