From the Guidelines
D-dimers are small protein fragments produced when blood clots break down in the body, serving as biomarkers for active blood clotting and measured through a blood test commonly used in clinical settings. They are particularly valuable for ruling out conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE) due to their high sensitivity, as noted in the guidelines for the diagnosis and management of patients with thoracic aortic disease 1. A normal or negative D-dimer result (typically less than 500 ng/mL, though reference ranges may vary between laboratories) generally indicates that a person is unlikely to have a blood clot. However, D-dimer levels can be elevated in many other conditions besides blood clots, including pregnancy, inflammation, cancer, recent surgery, and infections, which limits the test's specificity, as discussed in the American College of Chest Physicians evidence-based clinical practice guidelines 1.
Some key points to consider about D-dimers include:
- They are a sensitive but nonspecific marker for venous thromboembolism (VTE) 1
- A positive result is not useful in confirming the diagnosis of DVT, but a negative result can aid in the exclusion of this diagnosis 1
- D-dimer testing has less usefulness in hospitalized and other acutely ill patients due to the high frequency of false-positive results 1
- The test works because when fibrin (a protein involved in clot formation) is broken down by enzymes, it creates these distinctive fragments containing two D domains connected together, hence the name "D-dimer"
- Clinicians typically use D-dimer testing alongside clinical assessment tools and sometimes additional imaging studies to make diagnostic decisions about thrombotic disorders, as seen in the evaluation of acute aortic dissection (AoD) where significant elevations of D-dimer were seen in all patients with documented acute AoD 1.
In clinical practice, the use of D-dimer assays should be considered in patients where clinical suspicion of thrombotic disorders exists, to help identify those who do not require definitive imaging studies, although the efficacy and safety of this strategy have not been tested in a large clinical trial 1.
From the Research
Definition and Origin of D-Dimers
- D-Dimers derive from the degradation of cross-linked fibrin by plasmin 2
- They serve as a marker of coagulation and fibrinolytic system activation 2
Clinical Use of D-Dimers
- D-Dimer levels are used to exclude venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), especially when the pretest probability is low or intermediate 2, 3, 4, 5
- Guidelines recommend determining D-Dimer levels to avoid unnecessary imaging tests 2
- D-Dimer assays offer high sensitivity but low specificity, as levels can be elevated in conditions other than thrombosis and increase with age 2
Diagnostic Performance and Adjustments
- The diagnostic performance of D-Dimer assays can be improved by adjusting cutoffs according to patient characteristics such as age, pretest probability, pregnancy, renal function, or cancer 2
- Age-adjusted D-Dimer cutoffs can enhance the negative predictive value for DVT and PE 3
- Clinical probability-adjusted analyses can decrease false positive rates 3
D-Dimers in Disease Management and Prognosis
- D-Dimer levels can predict the clinical severity of COVID-19 and guide anticoagulation therapy 2
- Elevated D-Dimer levels during fibrinolytic therapy may serve as an early prognostic parameter for successful thrombolysis in PE 6
- D-Dimer levels are incorporated into prediction models for recurrent VTE to identify patients who may benefit from prolonged anticoagulation 2