D-Dimer

Aka: D-Dimer, D Dimer, D-Dimer Discriminatory Values in Pulmonary Embolism

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II. Indication

  1. Suspected Venous Thrombosis (DVT)
  2. Suspected Pulmonary Embolism (Low PE Probability)
    1. See Pulmonary Embolism Diagnosis
    2. Used in conjunction with non-invasive studies
    3. Reduces the need for angiography
  3. Consider using to risk stratify after Thromboembolism
    1. High D-Dimer at one month predicts recurrence

III. Efficacy

  1. Precautions
    1. Negative D-Dimer is reassuring if low probability
      1. Use more specific tests if suspicion is high
    2. Positive D-Dimer has minimal clinical value
      1. Positive does not raise DVT or PE Probability
  2. Test Sensitivity: 93% for Venous Thromboembolism
  3. Test Specificity: 25% for Venous Thromboembolism
  4. Negative Predictive Value: 99.5% if Low PE Probability
    1. Wells (2001) Ann Intern Med 135:98-107 [PubMed]

IV. Labs: Measurement

  1. ELISA assay and advanced turbidimetric
    1. Most sensitive D-Dimer Assays
  2. Rapid Latex Agglutination
    1. First generation tests were variable
    2. Second generation tests appear to be adequate and similar to ELISA

V. Labs: Quantitative Assay Units

  1. Fibrinogen Equivalent Units (FEU)
    1. Newer measurement units that replace the older DDU
    2. FEU = 2 * DDU
    3. FEU Units are used for cutoffs described below
  2. D-Dimer Units (DDU)
    1. Older standard units replaced by the newer FEU

VI. Mechanism

  1. Marker for intravascular coagulation
  2. D-Dimer is degradation product of Fibrin
  3. Indicates plasmin lysis of Fibrin
  4. Presence of D-Dimer suggests thrombosis

VII. Labs: Normal

  1. Negative Test: D-Dimer <500 ng/ml (default, lab reported normal cutoff)
  2. Discriminatory value in low risk Pulmonary Embolism
    1. Cutoff <500 ng/ml
      1. Adults at age <50 years
      2. First trimester pregnancy
      3. Any age with YEARS Score with any of 3 criteria present
      4. Moderate Probability on Wells Clinical Prediction Rule for PE (PEGeD protocol)
    2. Cutoff <600 ng/ml
      1. Adults at age 60 to 70 years (ACP age-adjusted D-Dimer)
    3. Cutoff <700 ng/ml
      1. Adults at age 70 to 75 years (ACP age-adjusted D-Dimer)
    4. Cutoff <750 ng/ml
      1. Second trimester pregnancy
    5. Cutoff <1000 ng/ml
      1. Adults at age >75 years
      2. Third trimester pregnancy
      3. Low Probability on Wells Clinical Prediction Rule for PE (PEGeD protocol)
      4. Any age with YEARS Score with all criteria absent
        1. In addition to YEARS Score, several studies have used D-Dimer 1.0 for low risk cases at any age
        2. Kearon (2019) N Engl J Med 381(22): 2125-34 +PMID:31774957 [PubMed]
        3. Freund (2021) JAMA 326(21): 2141-9 [PubMed]
  3. References
    1. ACP recommends Adult, age-adjusted D-Dimer cut-off
      1. Age >50 years old: Threshold = Age X 10 ng/ml
      2. Raja (2015) Ann Intern Med 163(9): 701-11 +PMID:26414967 [PubMed]
    2. D-Dimer Cutoff of 1000 ng/ml in age over 80 years old has 100% Test Sensitivity
      1. Polo Friz (2014) Thromb Res 133(3): 380-3 [PubMed]
    3. Pregnancy related D-Dimer cutoffs
      1. Chan (2010) J Thromb Haemost 8(5): 1004-11 +PMID:20128870 [PubMed]
      2. Ercan (2014) J Matern Fetal Neonatal Med 25:1-5 +PMID:25060670 [PubMed]
      3. Kovac (2010) Eur J Obstet Gynecol Reprod Biol 148(1): 27-30 +PMID:19804940 [PubMed]
    4. Pulmonary Embolism Graduated D-Dimer (PEGeD) Protocol
      1. Kearon (2019) N Engl J Med 381(22): 2125-34 [PubMed]

VIII. Causes: Increased D-Dimer (not specific)

  1. Venous Thromboembolism (true positive)
    1. Pulmonary Embolism
    2. Deep Vein Thrombosis
  2. Other causes (False Positives)
    1. Recent surgery (within prior 1 week)
    2. Myocardial Infarction
    3. Atrial Fibrillation
    4. Infection or Sepsis
    5. Cancer
    6. Concurrent systemic illness
    7. Oral Anticoagulant use
    8. Pregnancy
    9. Ongoing blood loss
    10. Decreased Renal Function
      1. Increased False Positive Rate when eGFR <60 ml/min (and esp. when <30 ml/min)

IX. Disadvantages: Circumstances in which D-Dimer is less useful

  1. Concurrent Anticoagulant use
  2. Comorbid cancer
  3. Age over 70 years
  4. Post-surgical status
  5. References
    1. Schutgens (2002) Am J Med 112:617-21 [PubMed]
    2. Lippi (2001) Clin Exp Med 1(3):161-4 [PubMed]

X. References

  1. Orman and Berg in Herbert (2015) EM:Rap 15(5): 10-11

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