PubMed · 12526126
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Robert L Prosser. 2003. De disappearing D-dimer.. https://doi.org/10.1067/mem.2003.27
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BACKGROUND: It may be safe to omit additional diagnostic testing in selected patients with suspected pulmonary embolism (PE) who have a negative D-dimer test, but this approach has never been evaluated in a randomized, controlled trial. OBJECTIVE: To determine if additional diagnostic testing can be safely withheld in patients with suspected PE who have negative erythrocyte agglutination D-dimer test results. DESIGN: Randomized comparisons in 2 subgroups of a prospective multicenter study. SETTING: 7 university hospitals. PATIENTS: 1126 outpatients or inpatients with suspected PE; of these, 456 patients with negative erythrocyte agglutination D-dimer test results were randomly assigned to the intervention groups. Patients were classified into 2 clinical probability groups: those with a low clinical probability of PE (low-probability group) and those with a moderate or high clinical probability of PE, a nondiagnostic ventilation-perfusion lung scan, and no evidence of proximal deep venous thrombosis on bilateral ultrasonography (moderate- or high-probability group). INTERVENTIONS: The experimental intervention for both probability groups was no further diagnostic testing for PE. The control intervention for the low-probability group was a ventilation-perfusion lung scan followed by ultrasonography of the proximal deep veins of the legs on the same day. If the lung scan was nondiagnostic, ultrasonography of the legs was repeated 7 and 14 days later. The control intervention for the moderate- or high-probability group was ultrasonography of the proximal deep veins of the legs after 7 and 14 days. In the control and experimental groups, anticoagulation was withheld or withdrawn if PE was not diagnosed. MEASUREMENTS: Symptomatic venous thromboembolism (VTE) during 6 months of follow-up. RESULTS: Prevalence of VTE was 15.2% in the 1126 enrolled patients. In the low-probability group, VTE occurred during follow-up in 0 of 182 patients who had no additional diagnostic testing and in 1 of 185 patients who had additional testing (difference, -0.5 percentage point [95% CI, -3.0 to 1.6 percentage points]). In the moderate- or high-probability group, VTE occurred during follow-up in 1 of 41 patients who had no additional diagnostic testing and in 0 of 41 patients who had additional testing (difference, 2.4 percentage points [CI, -6.4 to 12.6 percentage points]). LIMITATIONS: The authors could not enroll 2000 patients as originally planned; 3 randomly assigned patients did not receive the allocated intervention, and 7 received inadequate follow-up. Personnel who performed follow-up evaluations were not blinded to the results of diagnostic testing at enrollment or to allocation group assignments. CONCLUSION: In patients with a low probability of PE who have negative D-dimer results, additional diagnostic testing can be withheld without increasing the frequency of VTE during follow-up. Low clinical probability and negative D-dimer results occur in 50% of outpatients and in 20% of inpatients with suspected PE.
In this study, the importance of different domains of the fibrinogen molecule in the binding and assembly of a surface plasminogen (plgn) activator has been analyzed. This was achieved using SELDI technology that enabled dissociation of bound fragments from intact bacteria and accurate distinction between fibrinogen fragments based on their molecular mass. These studies indicate that Streptococcus pyogenes binds directly to human fibrinogen fragment D but not fragment E. The predominant surface proteins binding to fragment D were associated with the mrp gene product. Surface-associated fibrinogen fragment D was capable of anchoring a functional surface plgn activator complex. Taken together, these data indicated that fragment D of fibrinogen is necessary and sufficient to anchor a plgn activator complex on the surface of Streptococcus pyogenes.
This review summarizes recent information about the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) using noninvasive imaging tests, clinical assessment, and D-dimer assays, and describes how these tests can be employed in diagnostic testing algorithms for the investigation of patients with suspected DVT and PE. The clinical diagnosis of deep venous thrombosis is unreliable, but clinical prediction rules based on signs and symptoms do facilitate the categorization of patients into high, low, or medium risk categories. High sensitivity D-dimer assays further help in excluding cases but do not help in ruling in venous thromboembolism. D-dimer assays and clinical prediction rules also help in the diagnosis of pulmonary embolism. These assessments, along with objective imaging studies such as compression ultrasonography for DVT or computerized tomographic pulmonary angiograms for PE can be used in a systematic way to reliably rule in or exclude venous thromboembolism.