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    D-Dimer

    Hematological / Oncological, Respiratory

    Last Reviewed on Dec 16, 2022
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    By John Ward,Jethro Moneo

    Context

    • 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:
    • 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)

    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)

    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.

    Quality Of Evidence?

    Justification

    • The Well’s scores for DVT and for PE have high quality evidence as clinical decision-making tools which has been validated in numerous subsequent studies and meta-analyses.
    High
    • The 3-tiered approach for both adjusted-d-dimer DVT and PE diagnosis is moderate quality evidence based on excellent study design and magnitude of effect but lacks replication in subsequent trials.
    Moderate

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    Reference List

    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.


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