Abstract
Background:
The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear.
Purpose:
To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older.
Data Sources:
MEDLINE and EMBASE from 1 January 1988 to 13 February 2016.
Study Selection:
6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing.
Data Extraction:
Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool.
Data Synthesis:
The proportion of patients in whom imaging could be withheld based on a “PE-unlikely” Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged >50 years) d-dimer thresholds; their 3-month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) d-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted d-dimer testing was less than 3% in all examined subgroups.
Limitation:
Post hoc analysis, between-study differences in patient characteristics, use of various d-dimer assays, and limited statistical power to assess failure rate.
Conclusion:
Age-adjusted d-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed d-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies.
Primary Funding Source:
None.
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Author, Article, and Disclosure Information
Nick van Es,
From the Academic Medical Center, Amsterdam, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands; MD Anderson Cancer Center, Madrid, Spain; and University Medical Center Groningen, Groningen, the Netherlands.
Presented in part at the International Society of Thrombosis and Haemostasis in Toronto, Ontario, Canada, on 22 June 2015.
Acknowledgment: The authors thank Prof. Zwinderman (Academic Medical Center) for his valuable statistical advice and Prof. M. Righini (Geneva University Hospital, Geneva, Switzerland) for the use of patient data from the ADJUST-PE (Age-Adjusted d-Dimer Cut-off Levels to Rule Out Pulmonary Embolism) study.
Disclosures: Dr. Kamphuisen reports grants from the Dutch Thrombosis Foundation during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0031.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: See the Supplement. Statistical code: See the Methods section, Appendix, and Supplement. Data set: Requests can be sent to Dr. N. van Es (e-mail, n.
Corresponding Author: Nick van Es, MD, Academisch Medisch Centrum, Afdeling Vasculaire Geneeskunde, Room F4-136, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Current Author Addresses: Dr. N. van Es: Academisch Medisch Centrum, Afdeling Vasculaire Geneeskunde, Room F4-136, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Drs. van der Hulle, den Exter, Mos, Huisman, and Klok: Leids Universitair Medisch Centrum, Afdeling Trombose en Hemostase, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, Netherlands.
Dr. J. van Es: Onze Lieve Vrouwe Gasthuis Oost, Afdeling Longziekten, Oosterpark 9, 1091 AC, Amsterdam, the Netherlands.
Dr. Douma: Academisch Medisch Centrum, Afdeling Interne Geneeskunde, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Dr. Goekoop: HagaZiekenhuis, Afdeling Interne Geneeskunde, Leyweg 275, 2545 CH, Den Haag, the Netherlands.
Dr. Galipienzo: MD Anderson Cancer Center, Servicio de Anestesiologia y Reanimacion, Calle de Arturo Soria, 270, 28033 Madrid, Spain.
Dr. Kamphuisen: Universitair Medisch Centrum Groningen, Afdeling Interne Geneeskunde, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Dr. Büller: Academisch Medisch Centrum, Afdeling Vasculaire Geneeskunde, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Dr. Bossuyt: Academisch Medisch Centrum, Afdeling Klinische Epidemiologie, Biostatistiek en Bioinformatica, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Author Contributions: Conception and design: H.R. Büller, M.V. Huisman, P.W. Kamphuisen, F.A. Klok, T. van der Hulle, N. van Es.
Analysis and interpretation of the data: P.M. Bossuyt, H.R. Büller, P.L. den Exter, R.A. Douma, J. Galipienzo, R.J. Goekoop, M.V. Huisman, P.W. Kamphuisen, F.A. Klok, I.C.M. Mos, T. van der Hulle, J. van Es, N. van Es.
Drafting of the article: P.M. Bossuyt, H.R. Büller, N. van Es.
Critical revision for important intellectual content: H.R. Büller, P.L. den Exter, R.A. Douma, J. Galipienzo, R.J. Goekoop, P.W. Kamphuisen, F.A. Klok, I.C.M. Mos, T. van der Hulle, N. van Es.
Final approval of the article: P.M. Bossuyt, H.R. Büller, P.L. den Exter, R.A. Douma, J. Galipienzo, R.J. Goekoop, M.V. Huisman, P.W. Kamphuisen, F.A. Klok, I.C.M. Mos, T. van der Hulle, J. van Es, N. van Es.
Provision of study materials or patients: P.L. den Exter, R.A. Douma, J. Galipienzo, R.J. Goekoop, I.C.M. Mos.
Statistical expertise: P.M. Bossuyt, N. van Es.
Obtaining of funding: M.V. Huisman, P.W. Kamphuisen.
Administrative, technical, or logistic support : P.M. Bossuyt, H.R. Büller, P.W. Kamphuisen, T. van der Hulle, N. van Es.
Collection and assembly of data: P.W. Kamphuisen, F.A. Klok, T. van der Hulle, N. van Es.
This article was published at www.annals.org on 17 May 2016.
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