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Introduction:  Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking., Objectives:  To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m 2 ) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients., Methods:  We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia., Results:  We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%)., Conclusion:  BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Validated diagnostic algorithms are used to manage patients with suspected pulmonary embolism (PE). The recently published YEARS study proposed a simplified diagnostic strategy to reduce the use of computed tomography pulmonary angiography., Objectives: To externally validate this strategy in an independent cohort., Methods: We analyzed data from three previous prospective cohort studies of outpatients with suspected PE. We retrospectively applied the YEARS algorithm. The three YEARS clinical criteria are: clinical signs of deep vein thrombosis, hemoptysis, and PE as the most likely diagnosis. If zero YEARS criteria are met, a D-dimer < 1000 ng/mL will rule out PE. If ≥1 YEARS criteria are met, a D-dimer < 500 ng/mL will rule out PE., Results: Of the 3314 patients, 731 (22.1%) had PE. Applying the YEARS diagnostic algorithm, 1423 (42.9%) patients could have had PE ruled out without imaging. Of these patients, 17 (1.2%; 95% confidence interval 0.8-1.9) were diagnosed with PE at initial testing. All 17 had no YEARS item and a D-dimer < 1000 ng/mL. All 17 had a D-dimer level above their age-adjusted cutoff. Among the 272 patients with no YEARS criteria and a D-dimer < 1000 ng/mL but above their age-adjusted D-dimer cutoff, PE was diagnosed in 6.3% (17/272; 95% confidence interval 3.9-9.8)., Conclusion: We provide external validation of the YEARS diagnostic algorithm in an independent cohort. The rule appears to safely exclude PE. However, caution is required in patients with no YEARS item and a D-dimer < 1000 ng/mL but above their age-adjusted D-dimer cutoff., (© 2020 International Society on Thrombosis and Haemostasis.)

Background: In patients with suspected pulmonary embolism (PE) and a non-high pretest probability, the use of an age-adjusted D-dimer cutoff (AADD, <500 ng/mL up to 50 years, then $200 000/lost QALY was 79.4%. In sensitivity analyses, the DCER became <+$200 000/lost QALY only if, among patients with D-dimer below the AADD cutoff, the mortality of an undiagnosed PE was >6% or the prevalence of PE was >0.6%., Conclusions: The AADD cutoff results in a clinically nonsignificant decrease in QALY but important costs reductions. It is a decrementally cost-effective innovation, with a potential of cost savings of >$80 million per year for the United States health care system., (© 2020 International Society on Thrombosis and Haemostasis.)

Background: Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP., Methods: We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism., Results: A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9)., Conclusions: A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Multiple D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity for venous thromboembolism. These approaches are better established for pulmonary embolism., Objectives: We evaluated the diagnostic performance and compared the health system cost for previously suggested cutoffs and a new D-dimer cutoff for low-risk emergency department (ED) deep venous thrombosis (DVT) patients., Methods: We conducted a retrospective cohort study in two large EDs involving patients aged > 50 years who had low pretest probability for DVT and had a D-dimer performed. The outcome was a diagnosis of DVT at 30 days. We evaluated the diagnostic accuracy and estimated the difference in cost for cutoffs of 500 ng/mL and the age-adjusted (age × 10) rule. A derived cutoff of 1000 ng/mL was also assessed., Results: Nine hundred and seventy-two patients were included (median age 66 years; 59.5% female); 63 (6.5%) patients were diagnosed with DVT. The conventional cutoff of < 500 ng/mL demonstrated a sensitivity of 100% (95% confidence interval [CI] 94.3-100%) and a specificity of 35.6% (95% CI 32.5-38.8%). The age-adjusted approach increased specificity while maintaining high sensitivity. A new cutoff of 1000 ng/mL demonstrated improved performance: sensitivity 100% (95% CI 94.3-00%) and specificity 66.3% (95% CI 63.2-69.4%). Compared to the conventional approach, both the 1000 ng/mL cutoff and the age-adjusted cutoffs could save healthcare dollars. A cutoff of 1000 ng/mL could have saved 310 ED length of stay hours and $166,909 (Canadian dollars) in our cohort, or an average savings of 0.32 h and $172 per patient., Conclusions: Among patients aged > 50 years with suspected DVT, the age-adjusted D-dimer and a cutoff of 1000 ng/mL improved specificity without compromising sensitivity, and lowered the health care system cost compared to that for the conventional approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The "HERDOO2 rule" is a prospectively validated clinical decision rule used to identify low-risk women who can safely discontinue anticoagulants after completing 5-12 months of anticoagulant treatment for unprovoked venous thromboembolism. The VIDAS ® d-Dimer (DD) assay, a component of the rule, was used in the derivation and validation of the rule at half the usual diagnostic cut-point for exclusion of venous thrombosis. It is unknown if other commercial DD assays used at a corresponding cut-point will categorize patients at high concordance with the VIDAS ® DD., Objective: To determine if other available automated quantitative DD assays have high enough concordance with the VIDAS ® DD assay to allow their use within the "HERDOO2" clinical decision rule., Methods: Frozen plasma samples from a sub-set (n = 248) of female participants in the "HERDOO2" validation study were tested using five DD assays: VIDAS ® , Innovance ® , HemosIL ® , Tina-quant ® and Liatest ® , with duplicate testing for 50 samples. First, using the mean DD for 50 samples with duplicate results, we determined the optimal cut-point values for each test that corresponded with a VIDAS ® DD result of 250 μg/L using linear regression analysis. Next, kappa analysis was conducted on the DD results of the remaining 198 samples to determine concordance between each tested DD at the respective optimal cut-point and the VIDAS ® DD at 250 μg/L. In a separate analysis we determined the concordance at half the usual venous thrombosis exclusion cut-point., Results: Regression analysis of the DD results in 50 samples identified the optimal cut-point for each DD assay to match a VIDAS ® DD cut-point of 250 μg/L: Innovance ® 177 μg/L, Liatest ® 233 μg/L, Tina-quant ® 48 μg/L and HemosIL ® 56 μg/L. Next, in 198 different samples, the concordance of VIDAS ® DD (≥250 μg/L or <250 μg/L) was explored at the optimal cut-point of the other DD assays. The concordance was poor for all DD assays: Innovance ® (kappa 0.38 (95% CI, 0.26-0.51)), Liatest ® (kappa 0.38 (95% CI, 0.25-0.50)), HemosIL ® (kappa 0.36 (95% CI, 0.23-0.49)) and Tina-quant ® (kappa 0.30 (95% CI, 0.16-0.43)). Similar poor concordance was identified using half of the diagnostic DD cut-point for each tested assay: Innovance ® (kappa 0.44 (95% CI, 0.32-0.56)), Liatest ® (kappa 0.38 (95% CI, 0.25-0.51)), HemosIL ® (kappa 0.04 (95% CI, -0.01-0.08)) and Tina-quant ® (kappa 0.04 (95% CI, -0.004-0.07))., Conclusion: The "HERDOO2 rule" is the only prospectively validated clinical decision rule that can be used to identify low-risk women with unprovoked venous thrombosis who can safely discontinue anticoagulants. An important implementation issue is whether any commercial DD assay can be used in the HERDOO2 rule, and at what cut-point. Our analysis shows that the HemosIL ® , Innovance ® , Liatest ® and Tina-quant ® DD assays should not be used in the "HERDOO2" rule due to poor concordance with the VIDAS ® DD assay and unacceptable misclassification of women at high and low risk of recurrent venous thrombosis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Essentials The simplified Geneva score allows easier pretest probability assessment of pulmonary embolism (PE). We prospectively validated this score in the ADJUST-PE management outcome study. The study shows that it is safe to manage patients with suspected PE according to this score. The simplified Geneva score is now ready for use in routine clinical practice., Summary: Background Pretest probability assessment by a clinical prediction rule (CPR) is an important step in the management of patients with suspected pulmonary embolism (PE). A limitation to the use of CPRs is that their constitutive variables and corresponding number of points are difficult to memorize. A simplified version of the Geneva score (i.e. attributing one point to each variable) has been proposed but never been prospectively validated. Aims Prospective validation of the simplified Geneva score (SGS) and comparison with the previous version of the Geneva score (GS). Methods In the ADJUST-PE study, which had the primary aim of validating the age-adjusted D-dimer cut-off, the SGS was prospectively used to determine the pretest probability in a subsample of 1621 study patients. Results Overall, PE was confirmed in 294 (18.1%) patients. Using the SGS, 608 (37.5%), 980 (60.5%) and 33 (2%) were classified as having a low, intermediate and high clinical probability. Corresponding prevalences of PE were 9.7%, 22.4% and 45.5%; 490 (30.1%) patients with low or intermediate probability had a D-dimer level below 500 μg L -1 and 653 (41.1%) had a negative D-dimer test according to the age-adjusted cut-off. Using the GS, the figures were 491(30.9%) and 650 (40.9%). None of the patients considered as not having PE based on a low or intermediate SGS and negative D-dimer had a recurrent thromboembolic event during the 3-month follow-up. Conclusions The use of SGS has similar efficiency and safety to the GS in excluding PE in association with the D-dimer test., (© 2017 International Society on Thrombosis and Haemostasis.)

Over the last decades, important advances have been made in the diagnosis of venous thromboembolism (VTE). Current diagnostic strategies rely on the sequential use of non-invasive diagnostic tests, based on the pretest clinical probability of disease. Diagnostic tests include D-dimer measurement, leg vein compression ultrasonography, chest computed tomography pulmonary angiography, or ventilation perfusion (V/Q) lung scan. The safety and cost-effectiveness of these strategies have been extensively validated. They have been widely implemented in clinical practice and have replaced the historical gold standard diagnostic tests (venography and pulmonary angiography). However, new challenges arise, including a lower clinical suspicion threshold and concerns on potential over-diagnosis of VTE. Moreover, the diagnostic management remains suboptimal in many subgroups of patients with suspected VTE: patients with prior VTE, pregnant women, or elderly patients., (© 2015 International Society on Thrombosis and Haemostasis.)

Venous thromboembolism (VTE) is a potentially lethal clinical condition that is suspected in patients with common clinical complaints, in many and varied, clinical care settings. Once VTE is diagnosed, optimal therapeutic management (thrombolysis, IVC filters, type and duration of anticoagulants) and ideal therapeutic management settings (outpatient, critical care) are also controversial. Clinical prediction tools, including clinical decision rules and D-Dimer, have been developed, and some validated, to assist clinical decision making along the diagnostic and therapeutic management paths for VTE. Despite these developments, practice variation is high and there remain many controversies in the use of the clinical prediction tools. In this narrative review, we highlight challenges and controversies in VTE diagnostic and therapeutic management with a focus on clinical decision rules and D-Dimer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

Importance: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients., Objective: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE., Design, Settings, and Patients: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013., Interventions: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period., Main Outcomes and Measures: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result., Results: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings., Conclusions and Relevance: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism., Trial Registration: clinicaltrials.gov Identifier: NCT01134068.

D-dimer measurement is an important step in diagnostic strategies for venous thromboembolism. It allows the safe ruling out of the diagnosis with no need for imaging tests in approximately 30% of outpatients. However, the usefulness of d-dimer is limited in elderly patients; the likelihood of a negative d-dimer strongly decreases with age, making physicians reluctant to order the test. Several attempts to improve the performance of D-dimer in elderly patients have been pursued. Recently, an age-adjusted cutoff was derived; the optimal cutoff value (in µg/l) appears to be equal to the patient's age (in years) multiplied by ten in patients over 50 years of age with a low pretest clinical risk of venous thromboembolism. This age-adjusted cutoff value has been extensively and externally validated in retrospective studies that included mostly outpatients with suspected deep vein thrombosis or pulmonary embolism and used various quantitative D-dimer assays. All available studies confirmed the increased usefulness and similar safety of the age-adjusted cutoff compared with the conventional cutoff, the most important benefit being obtained in elderly patients. However, before any recommendation for clinical practice can be made, a prospective diagnostic management outcome study is lacking, in which all low clinical risk patients with D-dimer levels below their age-adjusted cutoff would be left untreated with no further diagnostic testing.

Background: D-dimer testing to rule out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in whom pulmonary embolism could be excluded. We retrospectively validated the efficacy of this cut-off combined with clinical probability for the exclusion of deep vein thrombosis., Design and Methods: Five management study cohorts of 2818 consecutive outpatients with suspected deep vein thrombosis were used. Patients with non-high or unlikely probability of deep vein thrombosis were included in the analysis; four different D-dimer tests were used. The proportion of patients with a normal D-dimer test and the failure rates were calculated using the conventional (500 μg/L) and the age-adjusted D-dimer cut-off (patient's age x 10 μg/L in patients >50 years)., Results: In 1672 patients with non-high probability, deep vein thrombosis could be excluded in 850 (51%) patients with the age-adjusted cut-off value versus 707 (42%) patients with the conventional cut-off value. The failure rates were 7 (0.8; 95% confidence interval 0.3-1.7%) for the age-adjusted cut-off value and 5 (0.7%, 0.2-1.6%) for the conventional cut-off value. The absolute increase in patients in whom deep vein thrombosis could be ruled out using the age-adjusted cut-off value was largest in patients >70 years: 19% among patients with non-high probability., Conclusions: The age-adjusted cut-off of the D-dimer combined with clinical probability greatly increases the proportion of older patients in whom deep vein thrombosis can be safely excluded.

Background: Age-adjusted D-dimer cut-off has recently been proposed to increase D-dimer usefulness in older patients suspected of pulmonary embolism (PE)., Objective: We externally validated this age-adjusted D-dimer cut-off using different D-dimer assays in a multicenter sample of emergency department patients., Methods: Secondary analysis of three prospectively collected databases (two European, one American) of patients suspected of having PE. D-dimer performance for ruling out PE was assessed by calculating negative likelihood ratio (nLR) for D-dimer with age-adjusted D-dimer cut-off (< age × 10 in patients over 50 years) and with conventional cut-off (< 500 μg dL(-1)). Test efficiency was assessed by the number needed to test (NNT) to rule out PE in one patient., Results: Among 4537 patients included, overall PE prevalence was 10.1%. In the overall population, nLR was 0.06 (95% confidence interval, 0.03-0.09) with conventional cut-off and 0.08 (0.05-0.12) with age-adjusted cut-off. Using age-adjusted cut-off, nLR was 0.08, 0.09 and 0.06 for Vidas(®) , Liatest(®) and MDA(®) assays, respectively. Use of age-adjusted cut-off produced a favorable effect on NNT in the elderly; the greatest decrease was observed in patients > 75 years: NTT halved from 8.1 to 3.6. The proportion of patients over 75 years with normal D-dimer was doubled (27.9% vs. 12.3%)., Conclusions: Our study shows that age-adjusted D-dimer had low nLR, allowing its use as a rule-out PE strategy in non-high pretest clinical probability patients, as well as using Vidas(®), Liatest(®) or MDA(®) assays. This age-adjusted cut-off increased clinical usefulness of D-dimer in older patients. A large prospective study is required to confirm these results., (© 2012 International Society on Thrombosis and Haemostasis.)

Objectives: In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed., Design: Retrospective multicentre cohort study., Setting: General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland. Patients 5132 consecutive patients with clinically suspected pulmonary embolism., Intervention: Development of a new D-dimer cut-off point in patients aged >50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets., Main Outcome Measures: The proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates., Results: The new D-dimer cut-off value was defined as (patient's agex10) microg/l in patients aged >50. In 1331 patients in the derivation set with an "unlikely" score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (<500 microg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged >70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets., Conclusions: The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded.

Clinical outcome studies have shown that it is safe to withhold anticoagulant therapy in patients with suspected pulmonary embolism (PE) who have a negative D-dimer result and a low pretest probability (PTP) either using a PTP model or clinical gestalt. It was the objective of the present study to assess the safety of the combination of a negative VIDAS D-dimer result in combination with a non-high PTP using the Wells or Geneva models to exclude PE. A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Seven studies (6 prospective management studies and 1 randomised controlled trial) reporting failure rates at three months were included in the analysis. Non-high PTP was defined as "unlikely" using the Wells' model, or "low/intermediate" PTP using either the Geneva score, the Revised Geneva Score, or clinical gestalt. Two reviewers independently extracted data onto standardised forms. A total of 5,622 patients with low/intermediate or unlikely PTP were assessed using the VIDAS D-dimer. PE was ruled out by a negative D-dimer test in 2,248 (40%, 95% confidence intervals [CI] 38.7 to 41.3%) of them. The three-month thromboembolic risk in patients left untreated on the basis of a low/intermediate or unlikely PTP and a negative D-dimer test was 3/2,166 (0.14%, 95% CI 0.05 to 0.41%). In conclusion, the combination of a negative VIDAS D-dimer result and a non-high PTP effectively and safely excludes PE in an important proportion of outpatients with suspected PE.

Background: Deep vein thrombosis (DVT) can be safely and reliably excluded in patients with a low clinical probability and a negative D-dimer result but the accuracy and utility of such a strategy is unclear in elderly patients., Objectives: We sought to compare the performance of the Wells pretest probability (PTP) model and D-dimer testing between patients of different age groups and to examine the utility of the two PTP model classification schemes (low/moderate/high vs. unlikely/likely) in excluding DVT in elderly outpatients., Patients/methods: Pooled analysis of databases from three prospective diagnostic studies evaluating consecutive outpatients with suspected DVT., Results: A total of 2696 patients were evaluated. DVT was diagnosed in 400 (15%) patients overall and in 50 out of 325 (15.5%) patients > or = 60 years old. The PTP distribution and the prevalence of DVT in each PTP category were similar among the different age groups. The negative predictive values of a low or unlikely PTP score in combination with a negative D-dimer result were 99% for all groups. A negative D-dimer in combination with a low or unlikely PTP excluded 21.7% and 31% of patients > or = 80 years old, respectively., Conclusions: The combination of a low or unlikely PTP with a negative D-dimer result can effectively and safely exclude DVT in a significant proportion of elderly outpatients. However, this clinical prediction rule needs to be prospectively validated with different D-dimer assays in this specific population.

Background: Multislice CT (MSCT) combined with D-dimer measurement can safely exclude pulmonary embolism in patients with a low or intermediate clinical probability of this disease. We compared this combination with a strategy in which both a negative venous ultrasonography of the leg and MSCT were needed to exclude pulmonary embolism., Methods: We included 1819 consecutive outpatients with clinically suspected pulmonary embolism in a multicentre non-inferiority randomised controlled trial comparing two strategies: clinical probability assessment and either D-dimer measurement and MSCT (DD-CT strategy [n=903]) or D-dimer measurement, venous compression ultrasonography of the leg, and MSCT (DD-US-CT strategy [n=916]). Randomisation was by computer-generated blocks with stratification according to centre. Patients with a high clinical probability according to the revised Geneva score and a negative work-up for pulmonary embolism were further investigated in both groups. The primary outcome was the 3-month thromboembolic risk in patients who were left untreated on the basis of the exclusion of pulmonary embolism by diagnostic strategy. Clinicians assessing outcome were blinded to group assignment. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00117169., Findings: The prevalence of pulmonary embolism was 20.6% in both groups (189 cases in DD-US-CT group and 186 in DD-CT group). We analysed 855 patients in the DD-US-CT group and 838 in the DD-CT group per protocol. The 3-month thromboembolic risk was 0.3% (95% CI 0.1-1.1) in the DD-US-CT group and 0.3% (0.1-1.2) in the DD-CT group (difference 0.0% [-0.9 to 0.8]). In the DD-US-CT group, ultrasonography showed a deep-venous thrombosis in 53 (9% [7-12]) of 574 patients, and thus MSCT was not undertaken., Interpretation: The strategy combining D-dimer and MSCT is as safe as the strategy using D-dimer followed by venous compression ultrasonography of the leg and MSCT for exclusion of pulmonary embolism. An ultrasound could be of use in patients with a contraindication to CT.

Limited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE). Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients with a malignancy. At cut-off values varying from 500 to 900 microg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI: 11% to 24%) to 30% (95% CI: 22% to 39%). The 3-month thromboembolic risk was 0% (95% CI: 0% to 18%) in cancer patients with a negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test's clinical usefulness.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Background: Single-detector-row computed tomography (CT) has a low sensitivity for pulmonary embolism and must be combined with venous-compression ultrasonography of the lower limbs. We evaluated whether the use of D-dimer measurement and multidetector-row CT, without lower-limb ultrasonography, might safely rule out pulmonary embolism., Methods: We included 756 consecutive patients with clinically suspected pulmonary embolism from the emergency departments of three teaching hospitals and managed their cases according to a standardized sequential diagnostic strategy. All patients were followed for three months., Results: Pulmonary embolism was detected in 194 of the 756 patients (26 percent). Among the 82 patients with a high clinical probability of pulmonary embolism, multidetector-row CT showed pulmonary embolism in 78, and 1 patient had proximal deep venous thrombosis and a CT scan that was negative for pulmonary embolism. Of the 674 patients without a high probability of pulmonary embolism, 232 (34 percent) had a negative D-dimer assay and an uneventful follow-up; CT showed pulmonary embolism in 109 patients. CT and ultrasonography were negative in 318 patients, of whom 3 had a definite thromboembolic event and 2 died of possible pulmonary embolism during follow-up (three-month risk of thromboembolism, 1.7 percent; 95 percent confidence interval, 0.7 to 3.9). Two patients had proximal deep venous thrombosis and a negative CT scan (risk, 0.6 percent; 95 percent confidence interval, 0.2 to 2.2). The overall three-month risk of thromboembolism in patients without pulmonary embolism would have been 1.5 percent (95 percent confidence interval, 0.8 to 3.0) if the D-dimer assay and multidetector-row CT had been the only tests used to rule out pulmonary embolism and ultrasonography had not been performed., Conclusions: Our data indicate the potential clinical use of a diagnostic strategy for ruling out pulmonary embolism on the basis of D-dimer testing and multidetector-row CT without lower-limb ultrasonography. A larger outcome study is needed before this approach can be adopted., (Copyright 2005 Massachusetts Medical Society.)