Issues Surrounding Age-Adjusted <scp>D</scp>-Dimer Cutoffs That Practicing Physicians Need to Know When Evaluating Patients With Suspected Pulmonary Embolism
Authors: Andrew J. Goodwin, Russell A. Higgins, Karen A. Moser, Kristi J. Smock, Wayne L. Chandler, Kandice Kottke-Marchant, Sarah K. Hartman, Oksana Volod, Alan F. Brown, Vandita P. Johari, Sharon Burr, Nataliya Polyakov, Dong Chen
Journal: Annals of Internal Medicine (2016)

Ideas and Opinions7 March 2017Issues Surrounding Age-Adjusted d-Dimer Cutoffs That Practicing Physicians Need to Know When Evaluating Patients With Suspected Pulmonary EmbolismCorrection(s) for this article:CorrectionsJul 2018Correction: Issues Surrounding Age-Adjusted D-Dimer CutoffsFREEAndrew J. Goodwin, MD, Russell A. Higgins, MD, Karen A. Moser, MD, Kristi J. Smock, MD, Wayne L. Chandler, MD, Kandice Kottke-Marchant, MD, PhD, Sarah K. Hartman, MD, Oksana Volod, MD, Alan F. Brown, MD, Vandita P. Johari, MD, Sharon Burr, MBA, MT, Nataliya Polyakov, MT, and Dong Chen, MD, PhDAndrew J. Goodwin, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Russell A. Higgins, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Karen A. Moser, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Kristi J. Smock, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Wayne L. Chandler, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Kandice Kottke-Marchant, MD, PhDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Sarah K. Hartman, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Oksana Volod, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Alan F. Brown, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Vandita P. Johari, MDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Sharon Burr, MBA, MTFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., Nataliya Polyakov, MTFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota., and Dong Chen, MD, PhDFrom University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2030 SectionsSupplemental MaterialAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This article has been corrected. The original version (PDF) is appended to this article as a Supplement.A recent best-practice advice paper from the Clinical Guidelines Committee of the American College of Physicians (ACP) provides an algorithmic approach that uses an initial clinical pretesting risk assessment (such as Wells or Geneva scores and Pulmonary Embolism Rule-out Criteria [PERC]), d-dimer testing for intermediate- and low-risk patients with positive PERC scores, and evaluation by imaging studies for high-risk patients and patients with positive d-dimer results (1). The authors recommend age-adjusted d-dimer (AADD) cutoffs based on several recently published studies (2), which demonstrated ...References1. Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD; Clinical Guidelines Committee of the American College of Physicians. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015;163:701-11. [PMID: 26414967]. doi:10.7326/M14-1772 LinkGoogle Scholar2. Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, et al. Diagnostic accuracy of conventional or age adjusted d-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ. 2013;346:f2492. [PMID: 23645857] doi:10.1136/bmj.f2492 CrossrefMedlineGoogle Scholar3. College of American Pathologists. Hematology and Coagulation Checklist. Northfield, IL: Coll American Pathologists; 2015. Google Scholar4. Olson JD, Adcock DM, Bush TA, De Moerloose P, Gardiner C, Ginyard VR, et al. Quantitative d-dimer for the exclusion of venous thromboembolic disease; approved guideline. CLSI document H59-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2011. Google Scholar5. Dempfle CE. Validation, calibration, and specificity of quantitative d-dimer assays. Semin Vasc Med. 2005;5:315-20. [PMID: 16302152] CrossrefMedlineGoogle Scholar6. Olson JD, Cunningham MT, Higgins RA, Eby CS, Brandt JT. d-Dimer: simple test, tough problems. Arch Pathol Lab Med. 2013;137:1030-8. [PMID: 23899057] doi:10.5858/arpa.2012-0296-CP CrossrefMedlineGoogle Scholar7. Longstaff C, Adcock D, Olson JD, Jennings I, Kitchen S, Mutch N, et al. Harmonisation of d-dimer—a call for action [Letter]. Thromb Res. 2016;137:219-20. [PMID: 26620264] doi:10.1016/j.thromres.2015.11.031 CrossrefMedlineGoogle Scholar8. Riley RS, Gilbert AR, Dalton JB, Pai S, McPherson RA. Widely used types and clinical applications of d-dimer assay. Lab Med. 2016;47:90-102. [PMID: 27016528] doi:10.1093/labmed/lmw001 CrossrefMedlineGoogle Scholar9. Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A, et al. Age-adjusted d-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014;311:1117-24. [PMID: 24643601] doi:10.1001/jama.2014.2135 CrossrefMedlineGoogle Scholar10. Mullier F, Vanpee D, Jamart J, Dubuc E, Bailly N, Douxfils J, et al. Comparison of five d-dimer reagents and application of an age-adjusted cut-off for the diagnosis of venous thromboembolism in emergency department. Blood Coagul Fibrinolysis. 2014;25:309-15. [PMID: 24247319] doi:10.1097/MBC.0000000000000020 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Vermont Medical Center, Burlington, Vermont; University of Texas Health San Antonio, San Antonio, and Baylor College of Medicine, Houston, Texas; Saint Louis University School of Medicine, St. Louis, Missouri; University of Utah and ARUP Laboratories, Salt Lake City, Utah; Seattle Children's Hospital, Seattle, Washington; Cleveland Clinic Foundation, Cleveland, Ohio; Cedars-Sinai Medical Center, Los Angeles, California; Baystate Medical Center, Springfield, Massachusetts; College of American Pathologists, Northfield, Illinois; and Mayo Clinic, Rochester, Minnesota.Disclosures: Dr. Goodwin reports personal fees from Haematologic Technologies outside the submitted work. Dr. Higgins reports personal fees from Werfen Instrumentation Laboratory and nonfinancial support from CAP outside the submitted work. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2030.Corresponding Author: Dong Chen, MD, PhD, 200 First Street, Southwest, Special Coagulation Laboratory, Division of Hematopathology, Mayo Clinic, Rochester, MN 55905; e-mail, chen.[email protected]edu.Current Author Addresses: Dr. Goodwin: Department of Pathology, University of Vermont Medical Center, 111 Colchester Avenue, Burlington, VT 05401.Dr. Higgins: Department of Pathology and Laboratory Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229.Dr. Moser: Department of Pathology, St. Louis University Medical School, 1402 South Grand Boulevard, St. Louis, MO 63104.Dr. Smock: ARUP Laboratories, 500 Chipeta Way, MSC 115-G04, Salt Lake City, UT 84108.Dr. Chandler: Department of Laboratories, Seattle Children's Hospital, OC 8 720, 4800 Sand Point Way Northeast, Seattle, WA 98105.Dr. Kottke-Marchant: Cleveland Clinic Foundation, 9500 Euclid Avenue, L-21, Cleveland, OH 44195.Dr. Hartman: Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USA 77030.Dr. Volod: Cedars–Sinai Medical Center, Beverly Pathology, 8700 Beverly Boulevard, Room 4711, Los Angeles, CA 90048.Dr. Brown: ARUP Laboratories, 1166 East Garfield Avenue, Apartment 3, Salt Lake City, UT 84105.Dr. Johari: Department of Pathology, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199.Ms. Burr and Ms. Polyakov: College of American Pathologists, 325 Waukegan Road, Northfield, IL 60093.Dr. Chen: Special Coagulation Laboratory, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905.Author Contributions: Conception and design: A.J. Goodwin, R.A. Higgins, K.A. Moser, K.J. Smock, W.L. Chandler, O. Volod, D. Chen.Analysis and interpretation of the data: A.J. Goodwin, R.A. Higgins, W.L. Chandler, D. Chen.Drafting of the article: A.J. Goodwin, R.A. Higgins, A.F. Brown, D. Chen.Critical revision for important intellectual content: A.J. Goodwin, R.A. Higgins, K.A. Moser, K.J. Smock, W.L. Chandler, D. Chen.Final approval of the article: A.J. Goodwin, R.A. Higgins, K.A. Moser, K.J. Smock, W.L. Chandler, K. Kottke-Marchant, S.K. Hartman, O. Volod, A.F. Brown, V.P. Johari, S. Burr, N. Polyakov, D. Chen.Administrative, technical, or logistic support: S. Burr, N. Polyakov.Collection and assembly of data: A.J. Goodwin, R.A. Higgins, K.J. Smock, D. Chen.This article was published at Annals.org on 27 December 2016. 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Wesorick, MD and Vineet Chopra, MD, MScReview of D-dimer testing: Good, Bad, and Ugly 7 March 2017Volume 166, Issue 5Page: 361-363KeywordsClinical laboratoriesD-dimerDisclosureFibrinogenFood and Drug AdministrationPathologistsPulmonary embolismResearch laboratoriesSafetySalts ePublished: 27 December 2016 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...