Enzyme-linked Immunosorbent Assay D-dimer Research Articles

Safe Exclusion of Deep Vein Thrombosis by a Rapid Sensitive ELISA D-dimer and Compression Ultrasonography in 1330 Outpatients With Suspected DVT

Of 1330 outpatients with suspected deep vein thrombosis (DVT), a normal enzyme-linked immunosorbent assay (ELISA) d-dimer (VIDAS) of <500 ng/mL was true negative in 382 of 384 and false negative in compression ultrasonography (CUS) in 2, indicating a sensitivity of 99.52% and a negative predictive value (NPV) of 99.48%, with a specificity of 36% irrespective of clinical score. In 1059 outpatients with no DVT, the CUS was positive for the alternative diagnoses (AD): Bakers cyst, muscle hematoma, or old DVT in 62 (5.8%); superficial vein thrombosis without DVT in 78 (7.4%), and leg edema or varices in 17%. A second CUS in 641 patients was positive in 26 (4.0%), indicating an NPV of 96% after a first negative CUS. The NPV of the combination of a negative first CUS and a ELISA d-dimer test <1000 ng/mL was 99.1% at a specificity of 66.9%. As this strategy is cost effective by reduction in the need to repeat CUS by 67%, we designed a novel algorithm for the safe exclusion and diagnosis of DVT and AD for subsequent evaluation in a large prospective study.

Does a Clinical Decision Rule Using D-Dimer Level Improve the Yield of Pulmonary CT Angiography?

This retrospective observational study from the Los Angeles Veterans Administration analyzed the impact of incorporating a clinical decision rule on the yield of pulmonary computed tomography angiography (CTA) in studying pulmonary embolism (PE). From December 2006 to November 2008, the authors implemented guidelines into the CTA order menu in the hospital's electronic medical record system. The ordering physician completed a checklist that generated a Wells score. If the Wells score was 5 or more, a pulmonary CTA using a 64-multi-detector CT scanner was ordered. If the Wells score was 4 or less, the ordering physician was required to obtain an enzyme-linked immunosorbent assay D-dimer level. For D-dimer levels≤500 ng/mL, no CTA was performed. For D-dimer>500, the patient went on to CTA. Patients had 3-month follow-up. During the study period, 261 pulmonary CTA studies were performed on 252 patients (8 patients underwent multiple CT scans), with 43 examinations (16.5%) positive for PE. In the 2 years before the implementation of the clinical decision rule, 196 CTAs were ordered, and 6 (3.1%) were positive for PE. Implementation of the study protocol resulted in a statistically significant increase in the positivity rate of 13.4%, (p<0.0001). In the positive-CTA group, the Wells score was significantly higher than in the negative-CTA group (5.5±2.4 vs 4.5±2.1, p=0.007). The mean D-dimer level was also significantly higher in the positive-CTA group (4956±2892 vs. 2398±2100, p<0.0001). In the study population, the authors found that a combination of a Wells score<4 and a D-dimer<1000 ng/mL had a negative predictive value of 1.0.

Diagnosis of Pulmonary Thromboembolism in Psychiatric Patients

To the Editor: Mortality from cardiovascular causes, including pulmonary thromboembolism, is the second most common cause of mortality in psychiatric patients.1 Intermittent shortness of breath, chest pain, and tachycardia are the most common symptoms of pulmonary thromboembolism,2 but many of these symptoms also accompany the experience of anxiety. The diagnosis of pulmonary thromboembolism in psychiatric patients is substantially confounded by the presence of anxiety symptoms. Case report. We treated a 21-year-old woman following an overdose of 40 mg of diazepam. At presentation in 2010, apart from tachycardia (105 bpm), examination revealed no abnormalities. She gave a history of depressive and anxiety symptoms since the birth of her son 18 months before presentation and was on duloxetine 60 mg/d. During her admission, on 4 occasions she reported feeling anxious and tired and was found to be hyperventilating. On those occasions, she was tachycardic (110–123 bpm) and tachypneic (20–24 breaths/min) and had an oxygen saturation of 97%–99% on room air. On each occasion, it was explained to her that she was experiencing anxiety and was given 2.5 mg of diazepam with good effect. She was reviewed by the ward physician, and apart from tachycardia examinations, revealed no abnormalities. A few hours prior to her discharge (after a 3-day admission), she again reported similar symptoms and collapsed. All efforts to resuscitate her failed. Pulmonary thromboembolism was identified on postmortem examination as responsible for causing her death. This patient had an intermediate clinical probability of pulmonary thromboembolism as per the Revised Geneva Score for the prediction of pulmonary thromboembolism, although she had none of the risk factors or symptoms defined therein.3 However, both the presence of a psychiatric disorder and exposure to antidepressants are risk factors for pulmonary thromboembolism not considered in this risk stratification.4 Also, as clarified from her family after her death, she had never experienced hyperventilation or tiredness when anxious previously. It is important to note that most psychiatric patients with anxiety can describe the experience of anxiety that is typical for them. On the basis of the above, we suggest that even in psychiatric patients with low or intermediate clinical probabilities for pulmonary thromboembolism, the presence of atypical anxiety symptoms should lead to a high index of suspicion for pulmonary thromboembolism. In this setting, a normal enzyme-linked immunosorbent assay D-dimer result avoids further testing.5 Further studies are needed to appropriately incorporate the presence of psychiatric disorder and exposure to antidepressants and/or antipsychotics in scoring systems for pulmonary thromboembolism.

Cost-Effectiveness of Strategies for Diagnosing Pulmonary Embolism Among Emergency Department Patients Presenting With Undifferentiated Symptoms

Symptoms associated with pulmonary embolism can be nonspecific and similar to many competing diagnoses, leading to excessive costly testing and treatment, as well as missed diagnoses. Objective studies are essential for diagnosis. This study evaluates the cost-effectiveness of different diagnostic strategies in an emergency department (ED) for patients presenting with undifferentiated symptoms suggestive of pulmonary embolism. Using a probabilistic decision model, we evaluated the incremental costs and effectiveness (quality-adjusted life-years gained) of 60 testing strategies for 5 patient pretest categories (distinguished by Wells score [high, moderate, or low] and whether deep venous thrombosis is clinically suspected). We performed deterministic and probabilistic sensitivity analyses. In the base case, for all patient pretest categories, the most cost-effective diagnostic strategy is to use an initial enzyme-linked immunosorbent assay D-dimer test, followed by compression ultrasonography of the lower extremities if the D-dimer is above a specified cutoff. The level of the preferred cutoff varies with the Wells pretest category and whether a deep venous thrombosis is clinically suspected. D-dimer cutoffs higher than the current recommended cutoff were often preferred for patients with even moderate and high Wells categories. Compression ultrasonography accuracy had to decrease below commonly cited levels in the literature before it was not part of a preferred strategy. When pulmonary embolism is suspected in the ED, use of an enzyme-linked immunosorbent assay D-dimer assay, often at cutoffs higher than those currently in use (for patients in whom deep venous thrombosis is not clinically suspected), followed by compression ultrasonography as appropriate, can reduce costs and improve outcomes.

Pretest probability estimation in the evaluation of patients with possible deep vein thrombosis

Introduction An estimation of pretest probability is integral to the proper interpretation of a negative compression ultrasound in the diagnostic assessment of lower-extremity deep vein thrombosis. We sought to determine the rate, method, and predictors of pretest probability estimation in such patients. Methods This cross-sectional study of outpatients was conducted in a suburban community hospital in 2006. Estimation of pretest probability was done by enzyme-linked immunosorbent assay d-dimer, Wells criteria, and unstructured clinical impression. Using logistic regression analysis, we measured predictors of documented risk assessment. A cohort analysis was undertaken to compare 3-month thromboembolic outcomes between risk groups. Results Among 524 cases, 289 (55.2%) underwent pretest probability estimation using the following methods: enzyme-linked immunosorbent assay d-dimer (228; 43.5%), clinical impression (106; 20.2%), and Wells criteria (24; 4.6%), with 69 (13.2%) patients undergoing a combination of at least two methods. Patient factors were not predictive of pretest probability estimation, but the specialty of the clinician was predictive; emergency physicians ( P < .0001) and specialty clinicians ( P = .001) were less likely than primary care clinicians to perform risk assessment. Thromboembolic events within 3 months were experienced by 0 of 52 patients in the explicitly low-risk group, 4 (1.8%) of 219 in the explicitly moderate- to high-risk group, and 1 (0.4%) of 226 in the group that did not undergo explicit risk assessment. Conclusions Negative ultrasounds in the workup of deep vein thrombosis are commonly interpreted in isolation apart from pretest probability estimations. Risk assessments varied by physician specialties. Opportunities exist for improvement in the diagnostic evaluation of these patients.

Pulmonary Embolism Despite Negative ELISA D-Dimer: A Case Report

Pulmonary embolus (PE) can be fatal, but is often treatable if recognized early. Unfortunately, the clinical presentation of PE is often variable and misleading. The D-dimer assay has recently come into favor as a method to exclude PE; however, this test has an acceptable safety margin only in low-risk populations. What is unclear is the exact composition of this low risk population. This is the report of a 26-year-old woman with over 2 weeks of chest pain and intermittent dyspnea. The patient was initially seen in the Emergency Department (ED) and hospitalized. She returned to the ED 2 weeks later with similar symptoms. Although enzyme-linked immunosorbent assay (ELISA) D-dimer assays were normal on the initial and subsequent ED visits, pulmonary embolism (PE) was diagnosed by computed tomography scan on the second visit. This report highlights the risk of misdiagnosing PE if relying solely on ELISA D-dimer for exclusion. The approach to PE should include a measure of clinical probability. This report documents the presentation of PE despite having two unremarkable ELISA D-dimer measurements, and highlights the importance of clinical suspicion.

Outcomes of High Pretest Probability Patients Undergoing D-Dimer Testing for Pulmonary Embolism: A Pilot Study

ELISA (enzyme-linked immunosorbent assay) D-dimer testing is commonly used in the evaluation of possible pulmonary embolism (PE) in the emergency department, but is not recommended in high pretest probability patients. Whether a negative ELISA D-dimer can safely rule out PE in these patients is not known, as there have been no large studies comparing ELISA D-dimer results and outcomes in high pretest probability patients. This was a prospective observational pilot study of emergency department patients evaluated for PE. Patients evaluated for PE had pretest probability assessed by the Wells PE Score. High pretest probability was defined as: dichotomized Wells Score > 4 points and patients with trichotomized Wells Score > 6 points. Patients had an ELISA D-dimer ordered by the treating physician. Pulmonary embolism was defined as: positive computed tomography scan, high probability ventilation/perfusion scan, positive pulmonary angiogram, or PE on 3-month follow-up. We calculated sensitivity, specificity, positive and negative predictive value, and likelihood ratios for the ELISA D-dimer. We prospectively enrolled 541 patients who underwent D-dimer testing for PE, of whom 130 patients had Wells Score > 4 and 33 patients had Wells Score > 6 (not mutually exclusive). Of subjects with Wells Score > 4, 23 (18%) were diagnosed with PE and 40 (31%) had a negative D-dimer. No patient with Wells Score > 4 (sensitivity 100%, 95% confidence interval [CI] 82%–100%; specificity 37%, 95% CI 28%–47%) or Wells Score > 6 (sensitivity 100%, 95% CI 63%–100%; specificity 56%, 95% CI 35%–76%) who had a negative D-dimer was diagnosed with PE. The likelihood ratio for a negative D-dimer was 0 for both the Wells > 4, and Wells > 6 groups, however, the upper limits of the confidence interval around the post-test probability for PE were 16% and 33%, respectively, for these high probability groups. In this pilot study, the rapid ELISA D-dimer had high sensitivity and negative predictive value even when applied to patients with high pretest probability for PE. However, with the post-test probability of PE still as high as 16–33% in the negative D-dimer groups, this precludes applying the results to patient care at present. Further testing is warranted to determine whether these findings can be safely incorporated into practice.

Managing suspected venous thromboembolism in a mixed primary and secondary care setting using standard clinical assessment and D-dimer in a noninvasive diagnostic strategy

Venous thromboembolism is a potentially lethal disease if not properly treated. Noninvasive strategies have become an attractive clinical option for effective diagnosis. There has been controversy, however, regarding the use of standard clinical rules in a primary care setting. The objective of the present study was to validate a noninvasive diagnostic strategy in an emergency unit giving assistance to patients with primary and secondary care needs. A total of 291 outpatients (primary and secondary care needs) with suspected venous thromboembolism attending the emergency unit of a general hospital from August 2002 to 2004 were retrospectively evaluated. The diagnostic strategy included assessment of risk for venous thromboembolism and a rapid quantitative enzyme-linked immunosorbent assay D-dimer test. Venous thromboembolism was ruled out in patients with a low-probability or intermediate-probability risk (or an unlikely diagnosis) and a negative D-dimer. The prevalence of venous thromboembolism was 8.2%. Patients with an unlikely diagnosis comprised 93.8% of the evaluations for deep venous thrombosis, and those with a low probability for pulmonary embolism comprised 81.4%. Proportions of patients with venous thromboembolic events observed were 7.2% in patients with an unlikely diagnosis of deep venous thrombosis and 3.0% in those with low probability for pulmonary embolism. The percentage of patients with a thrombotic event excluded using this strategy was 37% (positive predictive value 13%, negative predictive value 100%). In conclusion, this noninvasive clinical strategy is safe for ruling out venous thromboembolism, and excludes the need for imaging tests in about one-third of the patients in the population studied.

The role of enzyme-linked immunosorbent assay D-dimer in patients with acute coronary syndrome presenting with normal cardiac enzymes

Plasma D-dimer levels, the primary degradation product of cross-linked fibrin, are elevated in acute coronary syndrome (ACS). However, the role of D-dimer in patients presenting to the Emergency Department with ACS and normal cardiac enzymes is unknown. We conducted a prospective, observational study in the Emergency Department of a major tertiary university-affiliated center. The study included 124 patients presented to the Emergency Department with ACS and normal cardiac enzymes. Blood samples were collected and assayed for D-dimer levels with the enzyme-linked immunosorbent assay (ELISA) test. The D-dimer values were correlated with the clinical, laboratory and electrocardiographic findings on admission, as well as with the catheterization findings and with hospital length of stay. ELISA D-dimer levels positively correlated with sex, hypertension and smoking (r = -0.27, P = 0.002; r = 0.33, P = 0.0002; and r = -0.24, P = 0.007, respectively). Significant correlation was also observed between ELISA D-dimer and cardiac medications including beta-blocker (r = 0.22, P = 0.01), aspirin (r = 0.18, P = 0.04), nitrate (r = 0.20, P = 0.002), acute phase reactants fibrinogen (r = 0.45, P = 0.0001) and C-reactive protein (r = 0.29, P = 0.004), ischemic electrocardiographic changes (r = 0.21, P = 0.02) and length of stay (r = 0.29, P = 0.001). The catheterization findings were also correlated with the ELISA D-dimer levels (r = 0.31, P = 0.02). The ELISA D-dimer test may add important clinical data concerning patients with ACS and normal cardiac enzymes.

A Highly Sensitive ELISA D‐Dimer Increases Testing but Not Diagnosis of Pulmonary Embolism

To determine the effect of introducing a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer on the percentage of emergency department (ED) patients evaluated for pulmonary embolism (PE), the use of associated laboratory testing, pulmonary vascular imaging, and the diagnoses of PE. Patients evaluated for PE during three 120-day periods were enrolled: immediately before (period 1), immediately after (period 2), and one year after the introduction of a rapid ELISA D-dimer in the hospital. The frequency of ED patients evaluated for PE with any test, with D-dimer testing, and with pulmonary vascular imaging and the frequency of PE diagnosis during each time period were determined. The percentage of patients evaluated for PE nearly doubled; from 1.36% (328/24,101) in period 1 to 2.58% (654/25,318) in period 2 and 2.42% (583/24,093) in period 3. The percentage of patients who underwent D-dimer testing increased more than fourfold; from 0.39% (93/24,101) in period 1 to 1.83% (464/25,318) in period 2 and 1.77% (427/24,093) in period 3. The percentage of patients who underwent pulmonary vascular imaging increased from 1.02% (247/24,101) in period 1 to 1.36% (344/25,318) in period 2 and to 1.39% (334/24,093) in period 3. There was no difference in the percentage of patients diagnosed as having PE in period 1 (0.20% [47/24,101]), period 2 (0.27% [69/25,318]), and period 3 (0.24% [58/24,093]). In the study's academic ED, introduction of ELISA D-dimer testing was accompanied by an increase in PE evaluations, D-dimer testing, and pulmonary vascular imaging; there was no observed change in the rate of PE diagnosis.

Referent d-dimer enzyme-linked immunosorbent assay testing is of limited value in the exclusion of thromboembolic disease: result of a practical study in an ED

Objective The aim of this study was to assess in clinical practice the accuracy of a referent d-dimer enzyme-linked immunosorbent assay for the exclusion of venous thromboembolic disease (VTED). Patients and Methods An observational prospective study took place in an emergency department; 205 consecutive outpatients suspected of having VTED were included. Blood samples were collected at admission for VIDAS DD measurement. Venous thromboembolic disease was confirmed by standard clinical imaging. All patients were followed up at 3 months. Results Venous thromboembolic disease was confirmed in 57 patients (28%). The sensitivity and negative predictive value of a DD assay lower than 500 ng/mL were 78% (95% confidence interval = 67%-87%) and 84% (95% confidence interval = 73%-90%), respectively. Twelve patients had a false-negative DD with one or more of the following: ( a) symptoms reported for more than 15 days (n = 2), ( b) prior anticoagulation (n = 3), ( c) distal VTED (n = 5), or ( d) high clinical probability (n = 3). Conclusion In our cohort of patients, DD was less accurate than previously reported, with an upper estimate of the sensitivity of only 87%.

Value of D-Dimer Testing for the Exclusion of Pulmonary Embolism in Patients With Previous Venous Thromboembolism

D-dimer levels remain elevated in many patients after completion of a 6-month anticoagulant drug course for a first episode of venous thromboembolism (VTE), which may limit the clinical usefulness of D-dimer testing for ruling out a possible recurrence. We assessed the safety and usefulness of D-dimer testing in patients with suspected pulmonary embolism (PE) who had experienced a previous VTE. We analyzed data from 2 outcome studies that enrolled 1721 consecutive emergency department patients with clinically suspected PE. Information on the existence of a previous episode of VTE was abstracted from the database. All the patients underwent a sequential diagnostic workup, including an enzyme-linked immunosorbent assay D-dimer test and a 3-month follow-up. The proportion of confirmed PE was 24.1% (415/1719); PE was ruled out by a negative D-dimer test result in 32.7% (462/1411) of the patients without previous VTE but in only 15.9% (49/308) of the patients with previous VTE (P<.001). The 3-month thromboembolic risk was 0% (95% confidence interval, 0.0%-7.9%) in patients with previous VTE and a negative D-dimer test result. The 2-fold lower chance of a negative D-dimer test result in patients with previous VTE was independent of older age, active malignancy, fever, and recent surgery. In patients with suspected PE and previous VTE, a negative D-dimer test result seems to allow safely ruling out a recurrent event. However, the proportion of negative results is lower in such patients, definitely reducing the clinical usefulness of the D-dimer test in that subgroup.

Screening for Deep Vein Thrombosis and Pulmonary Embolism in Outpatients with Suspected DVT or PE by the Sequential Use of Clinical Score: A Sensitive Quantitative D-Dimer Test and Noninvasive Diagnostic Tools

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month follow-up. The negative predictive value (NPV) during 3 months of follow-up is 98.1 to 99% after a normal venogram, 97 to 98% after a normal compression ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is safe but 100 CUS must be repeated to find one or two CUS positive for deep vein thrombosis (DVT), which is not cost-effective and indicates the need to improve the diagnostic workup of DVT by the use of clinical score assessment and D-dimer testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to 99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than 99% for a negative CUS followed by either a negative SimpiRED test or an ELISA VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within 1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40 to 60%. Large prospective outcome studies demonstrate that with one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT, it is safe to withhold anticoagulant treatment, with a negative predictive value of 99.5%. This may indicates that CCUS is equal to serial CUS or the combined use of clinical score, D-dimer testing, and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with suspected PE and can replace both the ventilation perfusion scan and pulmonary angiography to safely rule in PE and to rule out PE with an NPV of > 99%. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for helical spiral CT by 40 to 50%.

The Effect of Changing from a Latex-agglutination D-dimer to an Enzyme-linked Immunosorbent Assay D-dimer on Emergency Physicians' Ordering Imaging Studies Practices to Evaluate for Pulmonary Embolism

The Effect of Changing from a Latex-agglutination D-dimer to an Enzyme-linked Immunosorbent Assay D-dimer on Emergency Physicians' Ordering Imaging Studies Practices to Evaluate for Pulmonary Embolism

Is the Current Diagnostic Cutoff for Enzyme-linked Immunosorbent Assay D-dimer Too Low?

Is the Current Diagnostic Cutoff for Enzyme-linked Immunosorbent Assay D-dimer Too Low?

An Emergency Department Guideline for the Diagnosis of Pulmonary Embolism: An Outcome Study

Objective: To assess the clinical outcome of patients suspected of pulmonary embolism (PE) following implementation of an emergency department (ED) diagnostic guideline. Methods: A prospective observational study of all patients suspected of PE who presented to the ED during a four-month study period. The authors' modification of the Charlotte criteria recommended D-dimer testing in those younger than 70 years of age with a low clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The negative predictive value of the overall diagnostic strategy and the test characteristics of D-dimer were calculated. Results: A total of 1,207 consecutive patients were evaluated for suspected PE; 71 (5.8%) were diagnosed with venous thromboembolism. One missed case of PE was identified on follow-up, yielding a negative predictive value of 99.9% (95% confidence interval [CI] = 99.5% to 100%). The missed case was a patient who presented with pleuritic chest pain and shortness of breath; a chest radiograph revealed pneumothorax, and the physician decided not to pursue the positive D-dimer result. The patient returned six weeks later with PE. Subgroup analysis of patients having D-dimer performed (n= 677) yields a sensitivity of 0.93 (95% CI = 0.77 to 0.98) and a specificity of 0.74 (95% CI = 0.70 to 0.77). Conclusions: Implementation of a PE diagnostic guideline in a community ED setting is safe and has improved the specificity of the enzyme-linked immunosorbent assay D-dimer test when compared with previous studies.

An Emergency Department Guideline for the Diagnosis of Pulmonary Embolism: An Outcome Study

To assess the clinical outcome of patients suspected of pulmonary embolism (PE) following implementation of an emergency department (ED) diagnostic guideline. A prospective observational study of all patients suspected of PE who presented to the ED during a four-month study period. The authors' modification of the Charlotte criteria recommended D-dimer testing in those younger than 70 years of age with a low clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The negative predictive value of the overall diagnostic strategy and the test characteristics of D-dimer were calculated. A total of 1,207 consecutive patients were evaluated for suspected PE; 71 (5.8%) were diagnosed with venous thromboembolism. One missed case of PE was identified on follow-up, yielding a negative predictive value of 99.9% (95% confidence interval [CI] = 99.5% to 100%). The missed case was a patient who presented with pleuritic chest pain and shortness of breath; a chest radiograph revealed pneumothorax, and the physician decided not to pursue the positive D-dimer result. The patient returned six weeks later with PE. Subgroup analysis of patients having D-dimer performed (n = 677) yields a sensitivity of 0.93 (95% CI = 0.77 to 0.98) and a specificity of 0.74 (95% CI = 0.70 to 0.77). Implementation of a PE diagnostic guideline in a community ED setting is safe and has improved the specificity of the enzyme-linked immunosorbent assay D-dimer test when compared with previous studies.

Clinical Usefulness of D-Dimer Depending on Clinical Probability and Cutoff Value in Outpatients With Suspected Pulmonary Embolism

We evaluated whether a highly sensitive D-dimer test is clinically useful and safe for ruling out pulmonary embolism (PE) in patients with a high clinical probability and whether adopting different cutoff values according to the clinical probability category might increase the proportion of patients in whom PE is ruled out. We retrospectively analyzed the databases of 2 outcome studies on the diagnosis of PE with a 3-month follow-up that included 1409 patients. We evaluated the usefulness of D-dimer testing by calculating the number needed to test to rule out one PE, and its safety by measuring the 3-month thromboembolic risk in patients not treated by anticoagulant agents based on a normal D-dimer level. The sensitivity of D-dimer was 100% in all clinical probability categories, but the number needed to test increased with increasing clinical probability of PE. The 95% confidence interval (0%-23%) of the 3-month thromboembolic risk (0%) among 13 of 121 patients with a normal D-dimer level and a high clinical probability of PE was wide. Increasing the cutoff value to 700 mug/L in patients with a low clinical probability would rule out PE in an additional 5% of the entire patient cohort at the expense of a lower sensitivity (93% [95% confidence interval, 83%-97%]). The safety of D-dimer testing in patients with a high clinical probability of PE is not established, and testing results are rarely negative in such patients. Increasing the enzyme-linked immunosorbent assay D-dimer cutoff value only marginally increased the test's usefulness.

A new rapid point-of-care D-dimer enzyme-linked immunosorbent assay (Stratus CS D-dimer) for the exclusion of venous thromboembolism.

To evaluate the performances of a new D-dimer assay, Stratus CS D-dimer (Dade Behring, Newark, Delaware, USA), for the exclusion of venous thromboembolism and to determine the best cut-off values. This test relies on a sandwich enzyme-linked immunosorbent assay with a fluorogenic substrate in a radial partition immunoassay system in a dedicated device. It does not require laboratory staff and the results are available within 18 min. Two hundred and ninety-one frozen samples from patients suspected of either deep venous thrombosis (n = 137) or pulmonary embolism (n = 154) were measured and the results compared with the VIDAS D-dimer New assay. There were 37 deep venous thrombosis (27%) and 49 pulmonary embolism (32%) samples. Receiver-operating characteristic curve analysis indicated that the cut-off value could be set at either 300 or 400 ng/ml Fibrinogen Equivalent Units (FEU). The coefficient of variation determined with a lyophilized low-level control plasma (305 ng/ml FEU) was 6%. With a cut-off at 300 ng/ml FEU, the sensitivity, the specificity and the negative predictive value were 100% [95% confidence interval (CI), 95.8-100], 33.1% (95% CI, 26.8-40) and 100% (95% CI, 94.7-100), respectively. Raising the cut-off to 400 ng/ml FEU, the corresponding figures were 96.5% (95% CI, 90.1-99.3), 46.3% (95% CI, 39.4-53.2) and 96.9% (95% CI, 91.3-99.4), respectively. At 400 ng/ml, three results were false-negative, one with both devices and two with the Stratus D-dimer only. Stratus D-dimer appears to be suitable for the exclusion of venous thromboembolism in the emergency room setting.

Volumetric Capnography as a Screening Test for Pulmonary Embolism in the Emergency Department

To compare the diagnostic performance of volumetric capnography (VCap), which is the plot of the expired CO(2) partial pressure against the expired volume during a single breath, with the PaCO(2) to end-tidal CO(2) (EtCO(2)) gradient, in the case of suspected pulmonary embolism (PE). Single-center, prospective study. Emergency department of a teaching hospital. A total of 45 outpatients with positive enzyme-linked immunosorbent assay d-dimer levels of > 500 ng/mL. The diagnosis of PE was confirmed in 18 outpatients according to a validated procedure based on the ventilation-perfusion lung scan and/or spiral CT scanning. Curves of VCap were obtained from a compact monitor connected to a computer. A sequence of four to six stable breaths allowed the calculation of the following several variables: alveolar dead space fraction; the ratio of alveolar dead space (VDalv) to airway dead space (VDaw); the VDalv to physiologic dead space (VDphys) fraction; the slope of phase 3; and the late dead space fraction (Fdlate) corresponding to the extrapolation of the capnographic curve to a volume of 15% of the predicted total lung capacity. The mean (+/- SD) PaCO(2)-EtCO(2) gradient was 5.3 +/- 0.7 mm Hg in the PE-positive group and 2.8 +/- 0.7 mm Hg in the PE-negative group (p = 0.019). Four variables of the VCap exhibited a statistical difference between both groups, as follows: the VDalv/VDaw fraction(;) the slope of phase 3; the VDalv/VDphys fraction; and the Fdlate, which was 8.2 +/- 3.3% vs -7.7 +/- 2.8%, respectively (p = 0.000011). The diagnostic performance expressed as the mean area under a receiver operating characteristic curve comparison was 75.9 +/- 7.4% for the PaCO(2)-EtCO(2) gradient and 87.6 +/- 4.9% for the Fdlate (p = 0.02). Fdlate, a variable of VCap, had a statistically better diagnostic performance in suspected PE than the PaCO(2)-EtCO(2) gradient. VCap is a promising computer-assisted bedside application of pulmonary pathophysiology. Future research should define the place of this technique in the diagnostic workup of PE, especially in the presence of positive d-dimers.