Background

Risk stratification tools like the Well’s and Geneva scores are useful for identifying patients in whom a venous thromboembolism (VTE) can be excluded with a negative D-dimer. This allows for decreased utilization of computed tomographic pulmonary angiography, V/Q scans and lower limb ultrasounds. However, the poor specificity of the D-dimer is associated with more patients getting imaged and the increased identification of sub-segmental clots of questionable significance. Additionally, it has been established the D-dimer levels increase with age further reducing the specificity of the test in patients over 50. Numerous studies have suggested that using an age adjusted D-dimer could improve the specificity of the test while preserving its sensitivity.

D-dimer is a protein fragment found in the blood after a blood clot is broken down by fibrin. 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.

Clinical Question

Can an age adjusted D-dimer assay using DDU (cut off 5x age for patients > 50 and 250 ng/ml < 50) be safely used instead of a standard cutoff in the diagnosis of VTE?

Population

All patients evaluated for possible VTE for whom a D-dimer level was sent who presented to the Emergency Department at York Hospital from 11/1/2013 and 7/31/14.

Outcomes

Primary: Diagnosis of VTE (DVT or PE) defined as a positive radiological test


Design

Single center retrospective review

Excluded

Patients who were not low risk by Wells criteria

Primary Results

  • Average age was 54; 43% were male and 79% had symptoms for 1 week
  • 1667 had a D-Dimer test sent
    • 1649 of those were sent to evaluate for VTE
    • PE evaluation: 986
    • DVT evaluation: 663
  • 1324 were thought to be low risk Wells
    • DVT: 384/663
    • PE: 940/986
  • Of the 1324 low risk Wells, 60 had confirmed VTE

Effect of Age-Adjusted D-dimer (Primary Outcome)

  • Use of age-adjusted D-dimer increased proportion of patients in whom VTE could be excluded without imaging
    • Standard cut-off: 64.9% with a negative D-dimer (859/1324)
    • Age-adjusted cut-off: 74.7% with a negative D-dimer (989/1324)
    • Absolute difference = 9.8%
  • Additional proportion excluded increased in age > 75
    • Standard cut-off: 37.6% with a negative D-dimer (91/242)
    • Age-adjusted cut-off: 63.6% with a negative D-dimer (154/242)
    • Absolute difference = 26%
  • No additional VTE were diagnosed in the group whose dimer went from positive using the standard cutoff to negative with age adjustment
  • Of the 130 patients with a negative age adjusted D-Dimer 25 CTPAs, 1 V/Q scan and 52 US were performed all of which were negative

Strengths

  • Uses a D-dimer assay in DDU as opposed to FEU as in other studies
  • Commonly used and well validated tools were applied
  • Assessed test characteristics in real world clinical setting

Limitations

  • This study took place at a single hospital center.
  • The study was a retrospective chart review
    • Wells score was only documented in 82% of patients being evaluated for DVT and 12% of patients being evaluated for PE
    • Reviewers extracted data to derive the Wels score but were aware of their clinical course, perhaps influencing what Wells group they were placed in
  • Limited demographics data reduces generalizability
  • Lack of imaging: Only about 50% of D-Dimer + had PE imaging
  • The follow up was limited to returns to this particular hospital, no mention of provider phone calls, local health systems data or other ways of tracking patient outcomes were made

Author's Conclusions

“For patients over the age of 50 years suspected of having VTE with a low pretest probability, increasing the D-dimer cut-off level to 5x the age increases the proportion of patients in whom VTE can safely be excluded without radiological imaging.”

Our Conclusions

Although this retrospective study has significant limitations, it provides evidence that an age adjusted D-dimer did not miss VTE in this group of patient’s. The effect of the age-adjusted D-dimer was more pronounced in the > 75 year old age group. This confirms the results of prior prospective studies looking at this question and adds to the existing literature through the use of a different assay.

Potential Impact To Current Practice

Emergency providers may consider using an age adjusted D-dimer with either FEUs or DDUs to rule out VTE in patient’s low risk for VTE using Wells criteria.

Bottom Line

Use of the age-adjusted D-dimer (with either FEUs or D-dimer units) increases the amount of low risk VTE patients who can be "ruled-out" for VTE without imaging and does not significantly increase false negatives.

Read More

Core EM: Age-Adjusted D-dimer in PE – The ADJUST-PE Study