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Correspondence |

Simplify d-Dimer Assay for Pulmonary EmbolismResponse FREE TO VIEW

Franck Verschuren, MD, PhD; Nicolas Delvau, MD; Frédéric Thys, MD, PhD
Author and Funding Information

Affiliations: Cliniques Universitaires Saint-Luc, Brussels, Belgium,  Carolinas Medical Center, Charlotte, NC

Correspondence to: Franck Verschuren, MD, PhD Acute Medicine, Cliniques Universitaires Saint-Luc, Av. Hippocrate, 1200 Brussels, Belgium; e-mail: Franck.verschuren@clin.ucl.ac.be



Chest. 2007;131(2):633-634. doi:10.1378/chest.06-1859
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Published online

We read with interest the article by Kline and coworkers1 (June 2006) regarding the diagnostic performance of the Simplify D-dimer assay (Agen Biomedical; Brisbane, Australia) for pulmonary embolism.1 The authors enrolled 2,302 emergency department patients and concluded that such a d-dimer could exclude this diagnosis with a posttest clinical probability of < 1% only in patients with a very low pretest clinical probability.

We agree with the authors that the diagnostic performance of the qualitative Simplify D-dimer, as expressed with a negative likelihood ratio of 0.27, is inferior to quantitative enzyme-linked immunosorbent d-dimer assays, which have been recently validated in a metaanalysis with a negative likelihood ratio of 0.08 (95% confidence interval, 0.04 to 0.18), allowing ruling out pulmonary embolism in all patients with low or moderate clinical pretest probability.2

But another disadvantage for the qualitative Simplify D-dimer, which has not been emphasized in the article, concerns its potential influence on the study population itself. Indeed, the low mean age of 44 years as well as the low rate of comorbid clinical conditions in the studied population do not match with the real situation of patients presenting a pulmonary embolism, as it has been evaluated by Aujesky et al3from > 10,000 embolic cases. Moreover, the very low prevalence of pulmonary embolism in the study (4.7%), the 99% rate of patients with low or intermediate clinical probability, as well as the 70% rate of negative d-dimer results, do not correspond to previously published outpatient populations.4We therefore suspect that this extremely low threshold for suspecting pulmonary embolism and ordering a d-dimer test is the consequence of using a “too” fast, easy, and cheap d-dimer assay, leading to excessive and inappropriate prescriptions, as it has been previously suggested, but to a lesser extent, even with enzyme-linked immunosorbent d-dimers.5 Too much feasibility may decrease efficiency.

The authors have no conflicts of interest to disclose.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Kline, JA, Runyon, MS, Webb, WB, et al (2006) Prospective study of the diagnostic accuracy of the Simplify D-dimer assay for pulmonary embolism in emergency department patients.Chest129,1417-1423. [PubMed] [CrossRef]
 
Roy, PM, Colombet, I, Durieux, P, et al Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism.BMJ2005;331,259-263. [PubMed]
 
Aujesky, D, Obrosky, DS, Stone, RA, et al Derivation and validation of a prognostic model for pulmonary embolism.Am J Respir Crit Care Med2005;172,1041-1046. [PubMed]
 
Perrier, A, Roy, PM, Sanchez, O, et al Multidetector-row computed tomography in suspected pulmonary embolism.N Engl J Med2005;352,1760-1768. [PubMed]
 
Verschuren, F, Hainaut, P, Thys, F, et al ELISA d-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician’s prescription.Acta Clin Belg2003;58,233-240. [PubMed]
 
To the Editor:

The authors appreciate the thoughtful letter by Dr. Verschuren. We acknowledge here, again, that the Simplify test (Agen; Brisbane, QLD, Australia) can safely rule out pulmonary embolism (PE) only in very low-risk patients. Dr. Vershuren’s main worry appears to focus on the young age of our cohort and the low prevalence of PE in it, citing work by Aujesky et al1 for comparison. The work by Aujesky et al1 was a retrospective, risk-stratification analysis of patients in the Pennsylvania Health Counsel database who had a International Classification of Diseases, ninth revision, discharge code indicating the diagnosis of PE. Inasmuch as advanced age confers an increased risk of PE, it is not surprising that patients in whom PE is diagnosed are older than the patients in our cohort, 95% of whom had been evaluated for possible PE but did not have PE.

That European researchers consistently find a prevalence of PE of > 20%, compared with the 5 to 10% observed in the United States, has previously provoked dialogues similar to this one.24 Several reasons explain this difference in prevalence. First, our sample was truly consecutive with virtually no missed subjects, such that we included even the lowest of low-suspicion workups, as long as the patient had a d-dimer test ordered for the purpose of excluding PE. Our research protocol played no role in the physicians’ decisions to order a d-dimer test. Second, when compared with the health-care system in the United States, the European health-care system enjoys a more functional primary care network, affording the opportunity for physician referral of many of the patients who are evaluated for PE in European emergency departments (EDs). Therefore, these partially prescreened populations who are evaluated for PE in European EDs should ostensibly have a higher underlying prevalence of PE compared with those in the United States. In urban America, emergency physicians evaluate an almost entirely unscreened population. Very few of our patients have reliable access to a primary care physician. Most patients have no choice except to visit the ED when they seek medical evaluation for symptoms such as chest pain or shortness of breath (or “breathing difficulties”). Finally, following hospital discharge, most of our patients are unable to access a physician if they have continued symptoms. As a result, the careful and diligent emergency physician in urban America must test liberally for PE, leading to a low prevalence. Indeed, approximately 3% of the 115,000 patients whom we care for each year in our own ED receive some type of diagnostic test for PE. In this setting, a rapid and safe point-of-care diagnostic test for PE remains an unmet imperative.

References
Aujesky, D, Obrosky, DS, Stone, RA, et al Derivation and validation of a prognostic model for pulmonary embolism.Am J Respir Crit Care Med2005;172,1041-1046. [PubMed] [CrossRef]
 
Le Gal, G, Bounameaux, H Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients.J Thromb Haemost2004;2,1244-1246. [PubMed]
 
Righini, M, Le Gal, G, Perrier, A, et al More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.J Thromb Haemost2005;3,188-189. [PubMed]
 
Kline, JA, Mitchell, AM, Kabrhel, C, et al More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.J Thromb Haemost2005;3,190-191
 

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References

Kline, JA, Runyon, MS, Webb, WB, et al (2006) Prospective study of the diagnostic accuracy of the Simplify D-dimer assay for pulmonary embolism in emergency department patients.Chest129,1417-1423. [PubMed] [CrossRef]
 
Roy, PM, Colombet, I, Durieux, P, et al Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism.BMJ2005;331,259-263. [PubMed]
 
Aujesky, D, Obrosky, DS, Stone, RA, et al Derivation and validation of a prognostic model for pulmonary embolism.Am J Respir Crit Care Med2005;172,1041-1046. [PubMed]
 
Perrier, A, Roy, PM, Sanchez, O, et al Multidetector-row computed tomography in suspected pulmonary embolism.N Engl J Med2005;352,1760-1768. [PubMed]
 
Verschuren, F, Hainaut, P, Thys, F, et al ELISA d-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician’s prescription.Acta Clin Belg2003;58,233-240. [PubMed]
 
Aujesky, D, Obrosky, DS, Stone, RA, et al Derivation and validation of a prognostic model for pulmonary embolism.Am J Respir Crit Care Med2005;172,1041-1046. [PubMed] [CrossRef]
 
Le Gal, G, Bounameaux, H Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients.J Thromb Haemost2004;2,1244-1246. [PubMed]
 
Righini, M, Le Gal, G, Perrier, A, et al More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.J Thromb Haemost2005;3,188-189. [PubMed]
 
Kline, JA, Mitchell, AM, Kabrhel, C, et al More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.J Thromb Haemost2005;3,190-191
 
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