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      Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts

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          Abstract

          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 age×10) μg/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 μg/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.

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          Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.

          P. S. Wells, D Anderson, M. Rodger … (2000)
          We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was 4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
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            Prediction of pulmonary embolism in the emergency department: the revised Geneva score.

            Grégoire Le Gal, Marc Righini, Pierre-Marie Roy … (2006)
            Diagnosis of pulmonary embolism requires clinical probability assessment. Implicit assessment is accurate but is not standardized, and current prediction rules have shortcomings. To construct a simple score based entirely on clinical variables and independent from physicians' implicit judgment. Derivation and external validation of the score in 2 independent management studies on pulmonary embolism diagnosis. Emergency departments of 3 university hospitals in Europe. Consecutive patients admitted for clinically suspected pulmonary embolism. Collected data included demographic characteristics, risk factors, and clinical signs and symptoms suggestive of venous thromboembolism. The variables statistically significantly associated with pulmonary embolism in univariate analysis were included in a multivariate logistic regression model. Points were assigned according to the regression coefficients. The score was then externally validated in an independent cohort. The score comprised 8 variables (points): age older than 65 years (1 point), previous deep venous thrombosis or pulmonary embolism (3 points), surgery or fracture within 1 month (2 points), active malignant condition (2 points), unilateral lower limb pain (3 points), hemoptysis (2 points), heart rate of 75 to 94 beats/min (3 points) or 95 beats/min or more (5 points), and pain on lower-limb deep venous palpation and unilateral edema (4 points). In the validation set, the prevalence of pulmonary embolism was 8% in the low-probability category (0 to 3 points), 28% in the intermediate-probability category (4 to 10 points), and 74% in the high-probability category (> or =11 points). Interobserver agreement for the score items was not studied. The proposed score is entirely standardized and is based on clinical variables. It has sustained internal and external validation and should now be tested for clinical usefulness in an outcome study.
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              Effects of age on the performance of common diagnostic tests for pulmonary embolism.

              Marc Righini, Catherine Goehring, Henri Bounameaux … (2000)
              The diagnosis of pulmonary embolism in the elderly is often difficult because of comorbid medical conditions, and perhaps also because diagnostic tests have a lower yield. We analyzed the diagnostic performance of common diagnostic tests for pulmonary embolism in different age groups. We analyzed data from two large studies that enrolled 1,029 consecutive patients presenting to the emergency department with clinically suspected pulmonary embolism. The clinical probability of pulmonary embolism (high [>/=80%], intermediate, or low [ /=80 years of age. The positive predictive value of a high clinical probability of pulmonary embolism was greater in the elderly (71% to 78% in those >/=60 years old versus 40% to 64% in those /=80 years old. The diagnostic yield of lower limb compression ultrasonography was greater in the elderly. The proportion of lung scans that were diagnostic (normal, near-normal, or high probability) decreased from 68% to 42% with increasing age. Age affects the performance of common diagnostic tests for pulmonary embolism and should be kept in mind when evaluating patients suspected of having this condition.
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                Author and article information

                Contributors
                : Role: physician
                : Role: physician
                : Role: physician
                : Role: physician
                : Role: physician
                : Role: professor
                : Role: physician
                : Role: professor
                : Role: professor
                : Role: professor
                Journal
                Journal ID (nlm-ta): BMJ
                Journal ID (publisher-id): bmj
                Title: BMJ : British Medical Journal
                Publisher: BMJ Publishing Group Ltd.
                ISSN (Print): 0959-8138
                ISSN (Electronic): 1468-5833
                Publication date Collection: 2010
                Publication date (Print): 2010
                Publication date (Electronic): 30 March 2010
                Volume: 340
                Electronic Location Identifier: c1475
                Affiliations
                [1 ]Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands
                [2 ]Department of Internal Medicine and Chest Diseases, CHU la Cavale Blanche, Equipe d’accueil 3878 (GETBO), Brest University Hospital, 29609 Brest, France
                [3 ]Division of Angiology and Haemostasis, Department of Internal Medicine, Geneva Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
                [4 ]Division of Internal General Medicine, Geneva Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
                [5 ]Department of Haematology, Erasmus Medical Centre, ‘s-Gravendijkwal 230, 3015 CE Rotterdam, Netherlands
                [6 ]Department of Emergency Medicine, University of Angers, F-49933 Angers Cedex 9, France
                Author notes
                Correspondence to: R A Douma R.A.Douma@ 123456amc.uva.nl
                Article
                Publisher ID: dour707976
                DOI: 10.1136/bmj.c1475
                PMC ID: 2847688
                PubMed ID: 20354012
                SO-VID: 4494f5e3-f3fd-4019-aa34-c28e04590a66
                Copyright © © Douma et al 2010
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                Date accepted : 6 January 2010
                Categories
                Subject: Research
                Subject: Epidemiologic studies
                Subject: Venous thromboembolism
                Subject: Pulmonary embolism

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

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