Original article
Causes of elevated D-dimer in patients admitted to a large urban emergency department

https://doi.org/10.1016/j.ejim.2013.07.012Get rights and content

Highlights

  • D-dimer was examined in ED patients with suspected venous thromboembolism (VTE).

  • A significant correlation was found between age and D-dimer.

  • Infection was the most frequent diagnosis, followed by VTE and syncope.

  • As compared with values < 1000 ng/mL, the OR for VTE was 8.5 for D-dimer > 3000 ng/mL.

  • D-dimer lacks specificity for diagnosing VTE in elderly patients with comorbidities.

Abstract

Background

Although the request for D-dimer is widespread in emergency departments (EDs), the causes of elevation and their relationship with D-dimer levels in patients with diagnostic values are uncertain.

Methods

In this retrospective investigation, the study population consisted of all patients who visited our large urban ED in the year 2012, for whom a D-dimer test was requested for excluding or diagnosing venous thromboembolism (VTE). Only patients with D-dimer values > 243 ng/mL were included, regardless of their pre-test clinical probability for VTE.

Results

The final study population consisted of 1647 patients. A significant positive correlation was found between age and D-dimer. Infection was the most frequent diagnosis (15.6%), followed by VTE (12.1%), syncope (9.4%), heart failure (8.9%), trauma (8.2%) and cancer (5.8%). D-dimer was higher in patients with VTE than in those with other diagnoses (2541 ng/mL vs 1030 ng/mL; p < 0.001). The frequency of VTE gradually increased from patients with values < 1000 ng/mL to those with D-dimer > 3000 ng/mL (4.1 vs 26.7%; p < 0.001). As compared with D-dimer values < 1000 ng/mL, the Odds Ratio for VTE was 8.5 for values > 3000 ng/mL.

Conclusions

These results show that D-dimer lacks specificity for diagnosing VTE, especially in elderly patients admitted to the ED with significant co-morbidities. In older patients, elevated values (> 1000 ng/mL) are more frequently associated with VTE, so the use of higher cut-offs may be advantageous.

Introduction

Venous thromboembolism (VTE), which comprehends deep venous thrombosis (DVT) and/or pulmonary embolism (PE), is an important cause of death and disability worldwide. According to recent statistics, the overall prevalence of VTE is around 422 cases per 100,000, with a constant trend of increase of approximately 26 cases per 100,000 every new year [1]. Nearly one third of the patients with symptomatic VTE are diagnosed with PE, whereas two thirds are diagnosed with DVT alone [2]. Although the prevalence is reportedly heterogeneous among different racial or ethnic cohorts, the frequency seems higher in Blacks, intermediate in Caucasians, and lower in Asians. The prevalence is also age-dependent, with an approximately 90-fold increase in patients older than 80 as compared with those aged less than 15 years. Although no definitive conclusions can be drawn about gender prevalence, it has been hypothesized that sex may not be an independent risk factor [3]. The severity of this pathology is confirmed by studies showing that mortality can be as high as 6% in patients with DVT and 12% in those with PE, respectively [2].

Several lines of evidence attest that a consistent number of emergency department (ED) visits are made by patients with a primary diagnosis of VTE [4], thus emphasizing the need to obtain an early and accurate diagnosis in order to establish appropriate care, optimize outcome and decrease overcrowding in emergency room. It has now been clearly established that the appropriate use of laboratory resources, along with clinical prediction rules, has greatly improved the diagnostic workout in patients presenting with suspected VTE [5], [6]. Despite some inherent limitations, comprehensively reviewed elsewhere [7], [8], D-dimer is now widely recognized as the biochemical gold standard in the diagnostic approach of VTE among the various diagnostic biomarkers that have been proposed and tested over the past decades [9], [10]. Although the request of D-dimer testing has thus become commonplace in all patients admitted to the ED with a consistent suspicion of VTE, irrespective of their pre-test probability of disease, analysis of clinical outcomes and relationship with D-dimer levels in large number of patients with diagnostic values is still limited, to the best of our knowledge [5]. As such, the aim of this study was to analyze D-dimer values and causes of an elevated D-dimer in patients admitted to a large urban emergency department.

Section snippets

Materials and methods

In this retrospective investigation, the study population consisted of all patients who visited the ED of the academic hospital of Parma in the year 2012, for whom a D-dimer test was requested by an emergency physician in order to exclude or reinforce a diagnostic suspicion of VTE according to clinical signs and symptoms (i.e., prediction rule based on Revised Geneva score or on Wells score), and displaying a value above the 243 ng/mL diagnostic cut-off for VTE of the local immunoassay,

Results

Overall, data about 1819 patients with a D-dimer value measured upon ED admission and exceeding the 243 ng/mL diagnostic cut-off for VTE were retrieved throughout the study period. One hundred seventy two patients were excluded from the analysis because the final diagnosis was unavailable, unclear or mixed, so the final study cohort was represented by 1647 patients (mean age = 77 ± 15 years, range = 25–102 years; 756 men and 891 women). The leading reasons for ED admission were suspected pneumonia

Discussion

The incorporation of D-dimer testing in the diagnostic approach of patients admitted to the ED with suspected VTE is now almost unavoidable [7], [8], [9]. According to current ACCP guidelines, D-dimer testing should be preferentially used over diagnostic imaging (CUS and/or TC) for the initial assessment of patients with suspected VTE, when pre-test probability (assessed either with the Revised Geneva score or the Wells score) is low. A non-diagnostic value of D-dimer in patients with low to

Conclusions

D-dimer lacks specificity for diagnosing VTE, especially in elderly patients admitted to the ED with significant co-morbidities. In older patients, elevated values are more 35 frequently associated with VTE, so the use of higher cut-offs may be considered.

Learning points

  • D-dimer was examined in ED patients with suspected venous thromboembolism (VTE).

  • A significant correlation was found between age and D-dimer.

  • Infection was the most frequent diagnosis, followed by VTE and syncope.

  • As compared with values < 1000 ng/mL, the OR for VTE was 8.5 for D-dimer > 3000 ng/mL.

  • D-dimer lacks specificity for diagnosing VTE in elderly patients with comorbidities.

Conflict of interests

All authors have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.

References (19)

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