Douma, R. A. et al. 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. BMJ 340, c1475

Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
BMJ (online) (Impact Factor: 17.45). 03/2010; 340(mar30 3):c1475. DOI: 10.1136/bmj.c1475
Source: PubMed


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.
Retrospective multicentre cohort study.
General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland. Patients 5132 consecutive patients with clinically suspected pulmonary embolism.
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.
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.
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.
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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    • "As current diagnostic strategies for PE include imaging (most often CTPA) in patients with positive D-dimers, lack of specificity of D-dimers in the elderly leads to a high proportion of these patients undergoing CTPA. The question of a higher D-dimer cut-off in elderly patients was raised a decade ago [34], but studies confirming the potential security of such a strategy by retrospectively applying age-adjusted cut-offs to large prospective cohorts of consecutive patients with suspected VTE were published between 2010 and 2012 [35] [36] [37] [38] [39]. A recent systematic review and meta-analysis of studies in patients with suspected VTE (PE and DVT) showed a dramatic decrease of the pooled specificity from 66.8% (95% CI 61.3–72) in patients b50 years to 14.7% (95% CI 11.3–18.6) in patients N80 years with the conventional D-dimer cut-off [40]. "
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    ABSTRACT: Elderly patients are a population not only at particularly high risk of venous thromboembolism including pulmonary embolism (PE), but also at high risk of adverse clinical outcomes and treatment-related complications. Major progresses have been achieved in the diagnosis and treatment of PE over the last two decades. Nevertheless, some of elderly patients' specificities still represent important challenges in the management of PE in this population, from its suspicion to its diagnosis and treatment, and are discussed in this review. Perspectives for the future are from a diagnostic point of view the potential implementation of age-adjusted d-dimer cut-offs that will allow ruling out PE in a greater proportion of elderly patients without the need for thoracic imaging. From a therapeutic point of view, acquisition of post-marketing clinical experience with the use of new oral anticoagulants is still necessary, and in the meantime, these drugs should be prescribed with great caution in thoroughly selected elderly patients.
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    • "The clinical PTP assessment using the Wells score provides greater accuracy in estimating the clinical PTP score, independent of clinician's experience, and allows the option for alternative diagnosis.[612] Although the sensitivity of the D-dimer test is high, the specificity is not sufficiently high enough for the test to be diagnostic;[13] however, D-dimer is a valuable tool in the exclusion of PE, as the negative predictive value of D-dimer is high.[14] The advantage of the VQ scan are a lower radiation dose than CTPA and the lack of need for iodinated contrast; therefore, VQ scanning is often considered as the preferred alternative chest imaging to CTPA.[1415] "
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    ABSTRACT: Aim of the study was to determine the accuracy of the clinical pretest probability (PTP) score and its association with lung ventilation and perfusion (VQ) scan. A retrospective analysis of 510 patients who had a lung VQ scan between 2008 and 2010 were included in the study. Out of 510 studies, the number of normal, low, and high probability VQ scans were 155 (30%), 289 (57%), and 55 (11%), respectively. A total of 103 patients underwent computed tomography pulmonary angiography (CTPA) scan in which 21 (20%) had a positive scan, 81 (79%) had a negative scan and one (1%) had an equivocal result. The rate of PE in the normal, low-probability, and high-probability scan categories were: 2 (9.5%), 10 (47.5%), and 9 (43%) respectively. A very low correlation (Pearson correlation coefficient r = 0.20) between the clinical PTP score and lung VQ scan. The area under the curve (AUC) of the clinical PTP score was 52% when compared with the CTPA results. However, the accuracy of lung VQ scan was better (AUC = 74%) when compared with CTPA scan. The clinical PTP score is unreliable on its own; however, it may still aid in the interpretation of lung VQ scan. The accuracy of the lung VQ scan was better in the assessment of underlying pulmonary embolism (PE).
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    • "In addition, even if the prognostic value of the D-dimer is independent of patient age and comorbidity [78], D-dimer levels are higher, on average, in the elderly [67] and age-specific D-dimer cut-points may increase its specificity [77]. Age-specific D-dimer cut-points, as proposed for the diagnostic use of D-dimer [79], may be helpful. Overall, additional research is needed to identify the optimal manner in which D-dimer can be used as a predictor of recurrent VTE. "
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    ABSTRACT: Opinion statement The management of patients with unprovoked venous thromboembolism is a common and challenging clinical problem. Although the initial antithrombotic management is well-established, there is uncertainty about the optimal long-term anticoagulant management, specifically whether patients should receive a short (i.e., 3- to 6-month) duration of anticoagulant therapy or indefinite anticoagulation. Factors that may be considered to estimate patients' risk for recurrent thromboembolism include the mode of initial clinical presentation, as deep vein thrombosis or pulmonary embolism, patient sex, antecedent hormonal therapy use, thrombophilia, D-dimer levels, and residual vein occlusion in patients with deep vein thrombosis. Many of these factors have been integrated into clinical prediction guides which stratify patients with unprovoked venous thromboembolism according to their risk for disease recurrence and, thereby, can assist clinicians in decisions about the duration of anticoagulation. The objective of this review is to consider the evidence relating to the clinical significance of purported risk factors and provide a practical case-based approach to guide decisions on duration of anticoagulation for patients with unprovoked venous thromboembolism.
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