From the Guidelines
D-dimer can be elevated due to various conditions, primarily those involving blood clot formation and breakdown, and it is essential to consider these causes in the context of patient care to prioritize morbidity, mortality, and quality of life outcomes. The most recent and highest quality study, 1, highlights that D-dimer levels are elevated in plasma in the presence of acute thrombosis due to simultaneous activation of coagulation and fibrinolysis. Common causes of elevated D-dimer include:
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Disseminated intravascular coagulation (DIC)
- Recent surgery
- Pregnancy, especially in the third trimester
- Cancer
- Severe infections or sepsis
- Heart attacks
- Advanced age
- Inflammatory conditions like rheumatoid arthritis
- Trauma
- Burns
- Liver disease
It is crucial to note that while D-dimer is sensitive for detecting clotting disorders, it is not specific, and an elevated level requires clinical correlation and often additional testing to determine the underlying cause. The test is most valuable when negative, as it helps rule out thrombotic conditions rather than definitively diagnosing them when positive. According to 1, the negative predictive value of D-dimer testing is high, and a normal D-dimer level renders acute PE or DVT unlikely. However, the positive predictive value of elevated D-dimer levels is low, and D-dimer testing is not useful for confirmation of PE.
In clinical practice, it is essential to consider the patient's overall clinical presentation and medical history when interpreting D-dimer results, as the test is not diagnostic on its own. The European Society of Cardiology guidelines, 1, emphasize the importance of clinical correlation and additional testing to determine the underlying cause of elevated D-dimer levels. By prioritizing morbidity, mortality, and quality of life outcomes, healthcare providers can use D-dimer testing as a valuable tool in the diagnosis and management of patients with suspected thrombotic conditions.
From the Research
Reasons for Elevated D-Dimer Levels
- D-Dimer is a biomarker of fibrin formation and degradation, and an elevated level can be associated with various clinical conditions, including:
- Elevated D-Dimer levels can also be associated with increased mortality and subsequent VTE across a broad variety of disease states 2
- Markedly elevated D-Dimer levels (> 5.0 µg/mL) can indicate the presence of coagulopathy, and rapid differential diagnosis is crucial for these patients 3
- Extremely elevated D-Dimer levels (> 5000 μg/l) are specific for serious illness, including VTE, sepsis, and/or cancer 5
Clinical Significance of Elevated D-Dimer Levels
- Elevated D-Dimer levels can be used as a negative predictor for thrombosis, with a negative predictive value (NPV) of 100% in patients with low D-Dimer levels 4
- D-Dimer testing has a reputation for being very non-specific, but an extremely elevated D-Dimer is uniquely associated with severe disease 5
- The interpretation of D-Dimer test results requires caution, and understanding the significance of D-Dimer in various disorders is necessary to avoid errors in diagnosis and treatment 6