• Appropriate use of D-dimer can save hospital resources and patient exposure to CT radiation/contrast in working up PE and DVT.
• D dimer is a byproduct of blood clotting and breakdown process.
• High sensitivity but low specificity for PE or DVT in low-risk populations
  • Always a “rule out” test – never used to “rule in” VTE.
• There are specific cases in which D-dimer can be helpful, and many in which it is useless or can potentially lead to patient harm through over investigation.
• There are many causes of D-dimer elevation other than VTE:
  • Thromboembolism (ex. stroke, MI, intracardiac thrombus, DIC).
  • Inflammation: infections, sepsis, COVID-19.
  • Surgery/Trauma.
  • Hepatic disease, renal disease.
  • Malignancy.
  • Vascular malformations, aortic dissection.
  • Pregnancy.

When to use D-dimer

• PE/DVT on differential diagnosis but:
  • PE unlikely based on Well’s Criteria for PE (<4.5).
  • DVT unlikely based on Well’s Criteria for DVT (<2).
• In the above situations, if d-dimer is negative, PE/DVT is rule out. If positive, further investigation via imaging is required.

Table 1. Well’s Scores. Adapted from Thrombosis Canada DVT and PE guidelines (2021)

When NOT to use D-dimer

• PE on differential but:
  • All PERC criteria are met – satisfactorily ruling out PE.
  • Well’s score for PE is >4.5.
  • Clinical suspicion is high enough for PE that CTPE or thoracic imaging will be ordered anyway.
  • Patient is hypotensive/unstable with SBP<= 90.
• DVT is on differential but:
  • Well’s score for DVT is ≥ 2.
  • Clinical suspicion is high enough for DVT that compressive ultrasound will be ordered anyway.

Table 2. Adapted from Thrombosis Canada Pulmonary Embolism Guidelines (2021)

Pearls

• Age adjustment for high sensitivity D-dimer increases the specificity of D-dimer testing for PE (evidence lacking for DVT).
  • In patients >50, D dimer is negative if less than patient age multiplied by 10 – for example if 80-year-old patient, negative is <800 µg/L..
    • If <50, cut off is <500 µg/L.
  • There is mounting evidence for a 3-tiered Well’s score for PE and DVT modifying D-dimer cut-off based on pre-test probability to further reduce unnecessary imaging:
    • PE: If low clinical probability (Wells score 0 to 4) and D-dimer <1000 µg/L, or moderate clinical probability (Wells score 4.5 to 6) and D-dimer <500 µg/L, PE can be ruled out.
    • DVT: If low clinical probability (Wells score -2 to 0) and D-dimer <1000 µg/L, or moderate clinical probability (Wells score 1 to 2) and D-dimer <500 µg/L, DVT can be ruled out.
      • Note: This idea has been cited in Thrombosis Canada guidelines as “safe” for both PE and DVT but has not yet implemented in their suggested algorithms for PE/DVT diagnosis.

Pitfalls:

• Over-reliance on clinical decision tools
  • Well’s score criteria for “alternative diagnosis more likely than PE” can change management in nearly all patients, which is entirely based on clinical judgement.
• Reflexive ordering of D-dimer without proper rationale to justify change in management based on results.
• There is insufficient evidence to support routine use of D-dimer in screening for aortic dissection.
• The use of D-dimer for DVT and PE has not been validated in pediatric populations.

1. PE: https://thrombosiscanada.ca/wp-uploads/uploads/2021/11/4.-Pulmonary-Embolism-Diagnosis_14November2021.pdf

   
   

2. DVT:https://thrombosiscanada.ca/wp-content/uploads/2021/07/2.-Deep-Vein-Thrombosis-Diagnosis_20July2021.pdf

   
   

3. Likelihood ratios/statistical analysis of clinical scoring systems combined with D-Dimers: http://blog.clinicalmonster.com/2020/02/28/working-up-pe-in-the-ed-negative-likelihood-ratios-and-fagan-nomograms/

   
   

1. Thrombosis Canada. (2021). Deep Vein Thrombosis: Diagnosis. https://thrombosiscanada.ca/wp-content/uploads/2021/07/2.-Deep-Vein-Thrombosis-Diagnosis_20July2021.pdf

   
   

2. Thrombosis Canada. (2021). Pulmonary Embolism: Diagnosis. https://thrombosiscanada.ca/wp-uploads/uploads/2021/11/4.-Pulmonary-Embolism-Diagnosis_14November2021.pdf

   
   

3. Kearon C, de Wit K, Parpia S, Schulman S, Afilalo M, Hirsch A, et al. Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability. New England Journal of Medicine. 2019 Nov 28;381(22):2125–34.

   
   

4. Kearon C, de Wit K, Parpia S, Schulman S, Spencer FA, Sharma S, et al. Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: prospective diagnostic management study. BMJ. 2022 Feb 15;376:e067378.

   
   

1. Thrombosis Canada DVT discharge sheet: https://thrombosiscanada.ca/wp-content/uploads/2016/05/M159-You-Have-a-DVT.pdf

   Thrombosis Canada PE discharge sheet: https://thrombosiscanada.ca/wp-content/uploads/2016/10/M159-You-Have-a-PE_Oct2016.pdf