Written by Amanda Mathews
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This systematic review and meta-analysis looked at diagnostic failures in patients with suspected acute PE and age-adjusted or clinical probability-adjusted D-dimer strategies. The pooled failure rate was 0.12% (95%CI 0.06–0.26%), leading the authors to conclude this is a safe and acceptable method for ruling out PE without CTPA.
D-dimer thresholds going up
Meta-analysis occurred for six studies including 12,194 patients. These were prospective diagnostic management studies enrolling at least 50 patients and applying an adaptive D-dimer strategy to select patients with suspected acute PE for imaging. Adaptive D-dimer strategies were classified as age-adjusted D-dimer thresholds or clinical probability-adjusted D-dimer thresholds (e.g., YEARS and PEGeD), applied in conjunction with a clinical prediction rule. Furthermore, a clinical follow-up of at least one month to identify any missed PE at baseline had to be scheduled. Primary outcome was diagnostic failure (PE, proximal DVT, or PE/unexplained death within 3 months). Studies including children or pregnant women were excluded.
When stratified by strategy, the pooled overall failure rate was 0.24% (95%CI, 0.10%–0.56%; pooled baseline prevalence of 12%, 95%CI 4%–29%; I2 98%) for YEARS-like strategies and 0.13% (95%CI, 0.03%–0.53%, pooled baseline prevalence of 11%, 95%CI 10%–12%; I2 94.7%) for age-adjusted D-dimer strategies. The pooled failure rate for patients with a D-dimer in the “adaptive window” (i.e. 500 ng/mL to age- or YEARS-adjusted upper limit) was 0.50% (95%CI 0.20–1.11%). The authors concluded, “These findings are consistent with the notion that the absolute number of missed clinically relevant events remains low when management is guided by validated adaptive algorithms.”
How will this change my practice?
The 2026 AHA guidelines support the use of age-adjusted D-dimer in the workup of suspected acute PE. I have been utilizing this in my clinical practice, and many of my colleagues and learners I work with have been doing the same. Included studies were conducted outside the United States, so national clinical guidelines may differ. It is great to see data that supports the very low miss rate of PEs when utilizing this approach. Age-adjusted D-dimer, in conjunction with the recent recommendation for the use of YEARS criteria to a broader range of patients (D-dimer threshold up to 1000 ng/mL for patients with no criteria), will lead to fewer patients needing CTPA to safely rule out acute PE.
Source
Safety of Age-Adjusted and Clinical Probability-Adjusted D-Dimer Cutoffs in Suspected Pulmonary Embolism: A Systematic Review and Meta-Analysis. Chest. 2026 Sep 25:S0012-3692(26)06720-6. doi: 10.1016/j.chest.2026.09.030. Epub ahead of print. PMID: 42790624.
