Non-high Clinical Probability Research Articles

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Systematic Review and Meta-analysis.

Background:Pulmonary embolism (PE), depending on the severity, carries a high mortality and morbidity. Proper evaluation, especially in patients with low probability for PE, is important to avoid unnecessary diagnostic testing.Objective:To review the diagnostic utility of conventional versus age-adjusted D-dimer cutoff values in patients 50 years and older with suspected pulmonary embolism.Methods:Systematic review with univariant and bivariant meta-analysis.Data sources:We searched PubMed, MEDLINE, and EBSCO for studies published before September 20th, 2020. We cross checked the reference list of relevant studies that compares conventional versus age-adjusted D-dimer cutoff values in patients with suspected pulmonary embolism.Study selection:We included primary published studies that compared both conventional (500 µg/L) and age-adjusted (age × 10 µg/L) cutoff values in patients with non-high clinical probability for pulmonary embolism.Results:Nine cohorts that included 47 720 patients with non-high clinical probability were included in the meta-analysis. Both Age-adjusted D-dimer and conventional D-dimer have high sensitivity. However, conventional D-dimer has higher false positive rate than age-adjusted D-dimer.Conclusion:Age-adjusted D-dimer cutoffs combined with low risk clinical probability assessment ruled out PE diagnosis in suspected patients with a decreased rate of false positive tests.

Cultivating a Better Understanding of COVID-19 Amidst a Shifting Landscape.

As COVID-19 swept across the globe, emergency physicians stood on the front lines of a pandemic unlike any seen in our lifetimes. In areas where cases surged, we rapidly assessed and stabilized large numbers of critically ill patients using the limited data available to us, for that is, fundamentally, what we do. In the beginning, we relied on first principles. Vital signs are vital. Isolate the infected. Intubate ARDS early.

Rapid Systematic Review: Age-Adjusted D-Dimer for Ruling Out Pulmonary Embolism

BackgroundPulmonary embolism (PE) is a disease diagnosed relatively frequently in emergency departments (EDs). Evidence suggests that improved decision making may decrease inappropriate testing, unnecessary radiation exposure, and non-beneficial treatment. Several studies have looked at the utility and safety of age-adjusting the D-dimer levels used to safely rule out PE. ObjectiveThis rapid systematic review sought to answer the question: Can an age-adjusted D-dimer be used to safely rule out PE in patients over 50 years old? MethodsWe performed a structured review of PubMed from January 2012 to January 2018 limited to reports involving human subjects and written in the English language and containing relevant keywords. The highest-quality studies were then reviewed in a structured format. ResultsOne hundred and eleven papers were identified for further review. Eight articles were determined to be appropriate for inclusion in this summary. These studies all used patient age (in years over 50) × 10 μg/L (fibrinogen equivalent units) as their definition of an age-adjusted D-dimer. ConclusionsAge-adjusted D-dimer cutoff values, in combination with a non-high clinical probability, is safe and effective to essentially rule out PE in ED patients.

P161 Assessment Of Age-adjusted D-dimer Cut-off Values In Investigating Venous Thromboembolism In Older Patients: A Retrospective Analysis

Introduction and objectives The specificity of D-dimer testing in detecting venous thromboembolism (VTE) appears to fall in older patients as D-dimer concentrations increase with age. There has been interest in the use of age-adjusted D-dimer cut-off values to increase the specificity in older patients. The objective of this study was to review the diagnostic accuracy of D-dimer testing in older patients with suspected VTE in our population, comparing conventional and age-adjusted D-dimer cut-off values. Methods A retrospective study from a large teaching hospital in the UK was undertaken. 389 data episodes were compiled from suspected VTE presentations during two months in 2013. Patients were assessed using a combination of clinical probability scores and D-dimer measurement (D-dimer HS assay, Instrumentation Laboratories). Conventional (230 ng/ml) and age-adjusted (age x 10 ng/ml) cut-off values were applied to patients ≥50 years, and specificity and sensitivity were calculated. Results (Table 1) Of the 389 presentations, 229 (58.9%) were from patients aged ≥50 years. 13 (11.5%) patients with positive D-dimers using the conventional cut-off, had VTE as confirmed by imaging tests. The sensitivity of the conventional D-dimer cut-off value was 100% in this older cohort, with a specificity of 53.7%. The age x10-adjusted cut-off improved specificity to 84.7%; however sensitivity was markedly reduced to 76.9%, with 3 patients (23.1%) with non-high clinical probability of VTE missed. Further analysis suggested that an age-adjusted cut-off factor of x3 would maintain sensitivity at 100%; however specificity was only 47.7%. Conclusions We have identified that an age-adjusted cut-off factor of x10 significantly increased D-dimer specificity in older patients; however the sensitivity of this test was unacceptably compromised. A cut-off factor of x3 maintained sensitivity, but specificity was unsatisfactory compared to conventional values, although still higher than in most published series. We conclude that we cannot use an age-adjusted cut-off of x10 in our ≥50 year old population using this assay. Further work is required to identify an appropriate cut-off, concentrating on the >75 year old patients only. This would help to reduce the number of unnecessary tests and anxiety in this vulnerable group of patients.

Biomarkers for diagnosis and prognostic stratification of aortic dissection: challenges and perspectives.

Aortic dissection (AD) is a severe vascular disease associated with major morbidity and mortality. The diagnosis of AD requires the performance of urgent aortic imaging exams such as computed tomography angiography, but the decision to perform these exams now essentially relies on clinical judgment. Several studies have identified a range of potential biomarkers stemming from the aortic extracellular matrix (matrix metalloproteinases, TGF-β, soluble elastin fragments), vascular smooth muscle cells (smooth muscle myosin heavy chain, creatine kinase, calponin), coagulation (D-dimer, platelets) and inflammation (C-reactive protein), whose circulating levels increase in patients affected by AD. Biomarkers of AD could be potentially used to screen patients with compatible symptoms, to identify patients at higher risk of AD, to rule out AD in patients with non-high clinical probability of AD and/or to obtain prognostic stratification of affected patients. This review will summarize available data and discuss present and future perspectives of circulating biomarkers for the diagnosis and prognostic stratification of AD.

Effects of impaired renal function on levels and performance of D-dimer in patients with suspected pulmonary embolism.

Clinical probability and D-dimer measurement play an essential role in the non-invasive diagnostic strategies for pulmonary embolism (PE). PE can be ruled out without further imaging in patients with non-high clinical probability and negative D-dimer. D-dimer level is increased in patients with renal impairment. Whether its diagnostic usefulness is maintained in these patients is not well determined. We aimed to evaluate the effects of renal impairment on diagnostic performances of D-dimer in patients with suspected PE. A retrospective analysis of 1,625 patients with suspected PE included in a multicentre prospective study was performed. D-dimer levels and percentages of patients with a negative D-dimer were compared between three subgroups according to glomerular filtration rate (GFR) estimated by the MDRD formula: ≥90 ml/min (normal renal function), 60-89 ml/min (mild renal impairment), 30-59 ml/min (moderate renal impairment). D-dimer levels increased and the proportion of negative D-dimer decreased significantly according to renal status: 46% negative D-dimer in patients with normal GFR, 31% in patients with mild renal impairment, 11% in those with moderate renal impairment, corresponding to number of patients needed to test to obtain one negative test of 2.2, 3.2 and 9, respectively. In conclusion, the clinical usefulness of D-dimer decreases with renal impairment. However, PE can still be ruled out by negative D-dimer in a substantial proportion of patients with non-high clinical probability, avoiding exposure to contrast media.

Age-Adjusted D-Dimer Cut-off Levels to Rule out Pulmonary Embolism: A Prospective Outcome Study

IntroductionD-dimer testing allows to safely rule out pulmonary embolism (PE) without imaging test in approximately one third of outpatients. However, D-Dimer test is less useful as age increases because of a lower specificity. We recently derived an age-adjusted D-dimer cut-off value (age-adjusted cut-off = patient's age x 10 in patients aged > 50 years, in μg/L), which allowed to significantly increase the proportion of patients in whom PE could be non-invasively excluded, without compromising safety. However, before being implemented in clinical practice, the safety of the age-adjusted cut-off should be verified in a management outcome study. MethodsWe designed a multicentre multinational prospective management outcome study. All consecutive outpatients seen in the emergency room of 22 centres in 4 countries with clinically suspected PE were assessed by a sequential diagnostic strategy based on the assessment of clinical probability, D-dimer measurement and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the usual threshold of 500 μg/L and their age-adjusted cut-off did not undergo CTPA and were left untreated and formally followed for a three-month period. ResultsBetween January 1, 2010 and February 28, 2013, we included 3,377 patients. Mean age was 62 years, and 57% were females. Overall, the proportion of confirmed PE was 18%. Among the 2,927 patients with a non-high clinical probability, 832 (28.4%) had a D-Dimer < 500 μg/L, and 345 additional patients (11.8%) had a D-Dimer comprised between 500 μg/L and their age-adjusted cut-off. During the 3-month follow-up period, out of the 345 patients with a D-Dimer between 500 μg/L and their age-adjusted cut-off, 18 patients received anticoagulation for another indication than PE. Of the remaining 327 patients, 7 died, and 7 underwent testing for suspected venous thromboembolism (VTE), of which one was confirmed. Therefore, the failure rate of the age-adjusted cut-off was 1/327: 0.3%, (95% CI 0.1 to 1.7%).Overall, 789 patients were aged 75 years or more, of them 697 had a non-high clinical probability. The proportion of patients with D-Dimer < 500 μg/L was 50/697 (7.2%). Another 161 patients had a D-Dimer above 500 μg/L and under their age-adjusted cut-off. Therefore, the proportion of patients > 75 with a negative D-Dimer using the age-adjusted cut-off was 211/697 (30.3%), of them none had a confirmed VTE during follow-up: 0.0%, (95%CI: 0.0 to 1.9%). ConclusionsOur study demonstrates that the age-adjusted D-Dimer cut-off may now be used in clinical practice in emergency room patients with suspected PE. Combined with clinical probability, it increases the number of patients in whom PE can be excluded without imaging test, and this is particularly true among elderly patients, with a four-fold increased yield of D-dimer. A D-Dimer above 500 μg/L but under the age-adjusted cut-off safely excludes the diagnosis of PE, with a 3-month risk of VTE in line with that observed in patients with a D-Dimer under 500 μg/L or after a negative pulmonary angiography, the gold-standard test for PE. Disclosures:No relevant conflicts of interest to declare.

Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis

Objective To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.Design Systematic review and bivariate...

The use of age-dependent D-dimer cut-off values to exclude deep vein thrombosis. Reply to "Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded". Haematologica 2012;97(10):1507-13

Following on from recent studies which suggest in patients over 50 years of age an age-dependent D-dimer cut off of ‘age multiplied by 10’, in conjunction with a non-high clinical probability, can be used to safely exclude pulmonary embolism (PE),[1][1]-[3][2] we read with interest the

Evaluation of the Stratus® CS Acute Care™ D-dimer assay (DDMR) using the Stratus® CS STAT Fluorometric Analyzer: A prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis

BackgroundD-dimer testing is an integral part of the diagnostic algorithm in excluding patients with venous thromboembolism. In this study, we prospectively evaluated the Stratus DDMR D-dimer test in patients suspected of pulmonary embolism (PE) and deep vein thrombosis (DVT). MethodsPatients suspected of venous thromboembolism were prospectively enrolled at four different clinical sites, with sodium citrate and lithium heparin plasma was tested using the DDMR D-dimer test on the Stratus CS analyzer. Results1,012 patients were enrolled for analysis, with 85/603 (14.1%) patients with PE and 80/443 (18.1%) with DVT, and four of the patients (0.4%) with PE and DVT. For the samples collected in 3.2% sodium citrate, the DDMR method had a sensitivity, specificity, and negative predictive value for VTE of 98.0%, 38.1%, and 99.1%, respectively. For the samples collected in lithium heparin, the DDMR method had a sensitivity, specificity, and negative predictive value (NPV) for VTE of 98.9%, 28.8%, and 99.4%, respectively. In PE, DDMR testing on citrate plasma had a sensitivity, specificity, and NPV of 98.8%, 39.5%, and 99.6%, respectively, while heparin samples had a sensitivity, specificity, and NPV for PE of 98.0%, 28.4%, and 99.1%, respectively. In DVT, citrate plasma had a sensitivity, specificity, and NPV for DVT of 97.5%, 32.0%, and 98.3%, respectively, while heparin samples had a sensitivity, specificity, and NPV for DVT of 100%, 27.8%, and 100%, respectively. ConclusionThe Stratus CS DDMR D-dimer can be used in those patients with non-high clinical pre-test probability for the exclusion of PE.

A positive compression ultrasonography of the lower limb veins is highly predictive of pulmonary embolism on computed tomography in suspected patients

The presence of a clot-- even asymptomatic-- in the proximal lower limb veins of a patient with clinically suspected pulmonary embolism (PE) provides evidence for venous thromboembolism and indicates anticoagulant therapy in such patients. We aimed at assessing the diagnostic performance of compression ultrasonography as compared to multi-slice computed tomography (MSCT) for the diagnosis of PE. We analyzed data from a large outcome management study that included consecutive outpatients referred to the emergency ward with clinically suspected PE. All high clinical probability patients, and all non-high clinical probability patients with a positive D-dimer test underwent both MSCT and CUS. Of the 756 included patients, 232 had PE ruled out on the basis of a negative D-dimer test, and 524 patients underwent both MSCT and CUS. PE was found in 187 out of the 511 patients with a conclusive MSCT. The sensitivity of CUS for the presence of PE on MSCT was 39% (95% confidence interval: 32 to 46%), and its specificity was 99% (95% CI:97 to 100%). Positive and negative likelihood ratios were 42.2 (95% CI: 13.5 to 131.9) and 0.6 (95% CI: 0.5 to 0.7), respectively. We conclude from that large study of unselected patients that CUS has high specificity but low sensitivity, for the diagnosis of PE at MSCT in suspected patients. It allows ruling in the diagnosis of PE without further invasive and/or expensive testing in suspected patients.

Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries

The objective of the study was to assess the clinical validity of a non-invasive diagnostic strategy for acute pulmonary embolism using clinical assessment combined with both ELISA D-dimer and complete lower limb ultrasound (US) examination of proximal and distal veins, before single-detector helical computed tomography (CT) of pulmonary arteries. We expected the strategy to have a high diagnostic exclusion power and to safely decrease the number of CT scans. This prospective, multicenter outcome study included 274 consecutive outpatients. All underwent a priori clinical probability, D-dimer and bilateral complete lower limb US assessments. Only patients with a high clinical probability and both tests negative, or positive D-dimer and negative US assessments, underwent CT. This was deemed necessary in 114 patients (42%). At baseline, venous thromboembolism (VTE) was detected in 110 patients (40%), either by US showing proximal (n=65) or distal (n=36) thrombosis, or by CT (n=9). Anticoagulant was withheld in the remaining patients with negative results in both D-dimer and US but a non-high clinical probability (n=59), or in both US and CT (n=90), or with negative US (n=6) and inadequate CT (n=9). All patients underwent a three-month clinical follow-up. VTE occurred in one patient with inadequate CT, yielding an incidence of 0.6% [95% confidence interval: 0.1-3.4]. No patient died from VTE or had major bleeding. Using clinical probability, ELISA D-dimer and complete US before helical CT is a safe strategy resulting in a substantial reduction in CT scans.

D-dimer Assays for the Exclusion of Venous Thromboembolism: Which Test for which Diagnostic Strategy?

SummaryD-dimer measurement has proven to be very useful to rule out deep vein thrombosis (DVT) and pulmonary embolism (PE) in symptomatic outpatients (1). The problem faced by many physicians is the choice and the position of the D-Dimer tests in the diagnostic work-up of patients suspected of venous thromboembolism (VTE). In the last and present issues of Thrombosis and Haemostasis, two very interesting studies addressing these questions were published.In the first paper (2), de Groot and colleagues evaluated, in a management study, the clinical utility of incorporating the SimpliRED assay in the diagnostic work-up of patients with suspected PE. Of the 245 study subjects, 59 did not receive anticoagulant therapy on the basis of a nondiagnostic lung scan, a normal D-dimer and a non-high clinical probability of PE. In the follow-up, only one patient experienced a thromboembolic event (which can be compared with the 6% of subsequent rate of VTE in the follow-up of the 54 patients with a normal perfusion lung scan). However, if SimpliRED D-dimer would have been used alone as a first exclusion step, 6 of 61 patients with proven PE had been missed (9.8%, 95% CI 3.7-20.2).