D-dimer is a soluble fibrin degradation product generated by plasmin-mediated breakdown of cross-linked fibrin, and its presence in plasma reflects activation of both coagulation and fibrinolysis. The clinical significance of D-dimer levels lies primarily in its use as a sensitive marker for the exclusion of acute venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, when combined with a low or intermediate pretest probability. In this context, a normal D-dimer level has a high negative predictive value, allowing safe exclusion of VTE without the need for imaging in appropriately selected patients.
D-dimer is also a key component in the diagnosis and monitoring of disseminated intravascular coagulation (DIC), as elevated levels indicate ongoing fibrin formation and breakdown, and is incorporated into the ISTH DIC scoring system. However, D-dimer is a nonspecific marker and can be elevated in numerous other conditions, including infection, inflammation, malignancy, trauma, pregnancy, and advanced age, which limits its positive predictive value for thrombosis.
In summary, the main clinical significance of D-dimer is its utility as a rule-out test for VTE in low-risk patients and as a marker of coagulation activation in DIC and other prothrombotic states. Elevated D-dimer levels are not specific for thrombosis and must be interpreted in the context of the clinical scenario and pretest probability.
For larger image, click here.
What is a D-dimer?
- D-dimer is a fibrin degradation product — a small protein fragment that results from the breakdown of a blood clot.
- Specifically, it comes from crosslinked fibrin that has been cleaved by plasmin during fibrinolysis.
- Its name comes from the fact that it’s composed of two D fragments of the fibrin protein.
How is it measured?
- Typically by ELISA-based or latex agglutination assays.
- Reported in ng/mL, μg/mL, or fibrinogen equivalent units (FEU).
- Most labs use a cutoff of 500 ng/mL FEU to rule out clot.
When is D-dimer useful?
- Ruling out venous thromboembolism (VTE) in low pretest probability patients
- Pulmonary embolism (PE)
- Deep vein thrombosis (DVT)
- If D-dimer is negative, VTE is very unlikely.
- Evaluating for Disseminated Intravascular Coagulation (DIC)
- Elevated D-dimer is part of the ISTH DIC scoring system
- Monitoring some disease states
- D-dimer may be tracked in COVID-19, cancer, or disseminated malignancy as a surrogate marker for thrombotic activity
When is it not helpful? (i.e., nonspecific elevations):
- D-dimer can be elevated in many conditions, including:
- Recent surgery or trauma
- Pregnancy
- Inflammation or infection
- Liver disease
- Cancer
- Aging (baseline levels rise with age)
- That’s why it’s best used when the pretest probability is low — a normal D-dimer can safely exclude clot, but a positive result does not confirm it.
Key Takeaway:
- D-dimer is best used as a rule-out test, not a rule-in test.