Age Adjusted D-dimer

For our next installment of Clinical Conundrums, we are going to address the issue of the Age Adjusted D-dimer in our hospital. Can we age adjust the SIUH (230) D-dimer for appropriate patients with suspected PE?Take a read and, perhaps, your practice will be changed!

Can you age adjust the SIUH D-dimer for appropriate patients with suspected PE?

Bottom Line Up Top: You can age adjust both D-dimer assays for appropriate patients with suspected pulmonary embolism. Link to age adjusted Calculator for both assays: MD Calc

Clinical Scenario: An 81-year-old female PMHx HTN, DM, remote history of breast cancer who presents to the ED with shortness for the past 2 days. She denies any recent fever, chills, or sick contacts. Patient has no history of DVT or PE. On exam, VS unremarkable except for a heart rate of 105. The resident identifies the patient as low-risk for PE via Wells score and orders a D-dimer. The attending is upset that the resident sent the test without telling them because “it’s always positive” but lets the resident ride it out. The D-dimer comes back “high” from the lab at 270 ng/mL. The resident asks the attending if we could age-adjust the D-dimer and end the workup for PE. What Your Gut Says: You can age adjust the D-dimer assay that other hospitals have, which have a cut off of 0.5 µ/mL or 500 ng/mL, but cannot be used in D-dimers with cutoffs of 230 µg/mL. Maybe in a different life or different hospital system this would work.

Background: D-dimer is a protein fragment found in the blood after a blood clot is broken down. This test is highly sensitive and can be used to “rule out” appropriate patients for Venous Thromboembolism (VTE). However, specificity is low, leading to a high number of false-positives and can increase the CTPA rate. D-dimer levels increase with age further reducing the specificity of the test in patients over 50. Most labs, and thus the vast majority of published studies, report D-dimer in fibrinogen equivalent units (FEUs). The common cutoff for this test is 500 ng/ml. Some laboratories use assays that report D-dimer units (DDU) where the cutoff is commonly set at 230 ng/ml. Thus, roughly 2 FEUs are equal to 1 DDU.

What The Evidence Says:

The Age-Adjusted D-dimer

There is strong evidence that we can safely use the age-adjusted D-dimer for appropriate patients for work up for VTE. Numerous studies have shown that using an age adjusted D-dimer could improve the specificity of the test while preserving its sensitivity. A summary of studies looking at the conventional D-dimer against the age-adjusted D-dimer was done by Wolf et al. showing comparable sensitivities for the conventional and age-adjusted values:

Bottom Line: The available evidence supports the use of an age-adjusted D-dimer, with either assay (FEUs or DDUs), to rule out VTE in patients that are low risk by Wells criteria. The use of the age-adjusted D-dimers decreases the number of PE studies needed in the Emergency Department and does not significantly increase false negatives. Choose the appropriate assay when age-adjusting this test.

Bonus Pearls: The 230 µg/mL D-dimer Reference Card

Read More

CORE EM: Age Adjusted D-dimer

REBEL EM: The YEARS Study – Simplified Diagnostic Approach to PE

REBEL EM:The Pragmatic Combination of YEARS Score and Age-Adjusted D-Dimer

References

American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Thromboembolic Disease:; Wolf SJ, Hahn SA, Nentwich LM, Raja AS, Silvers SM, Brown MD. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease. Ann Emerg Med. 2018 May;71(5):e59-e109. Doi: 10.1016/j.annemergmed.2018.03.006. PMID: 29681319.

Jaconelli T, Eragat M, Crane S. Can an age-adjusted D-dimer level be adopted in managing venous thromboembolism in the emergency department? A retrospective cohort study. Eur J Emerg Med. 2018 Aug;25(4):288-294. doi: 10.1097/MEJ.0000000000000448. PMID: 28079562.

Parks C, Bounds R, Davis B, Caplan R, Laughery T, Zeserson E. Investigation of age-adjusted D-dimer using an uncommon assay. Am J Emerg Med. 2019 Jul;37(7):1285-1288. doi: 10.1016/j.ajem.2018.09.035. Epub 2018 Sep 27. PMID: 30291035; PMCID: PMC8006071.

Gutovitz S, Phelps K, Broussard I, Shah V, Hart L, Root P. A Tale of Two D-Dimers: Comparison of Two Assay Methods to Evaluate Deep Vein Thrombosis or Pulmonary Embolism. J Emerg Med. 2022 Sep;63(3):389-398. doi: 10.1016/j.jemermed.2022.04.006. Epub 2022 Sep 10. PMID: 36096961.

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