From the Guidelines
Elevated D-dimer levels are a significant indicator of increased thrombin generation and potential mortality, particularly in patients with COVID-19, and hospital admission should be considered even in the absence of other severe symptoms if D-dimer levels are markedly raised. This is based on the findings of a study published in the Journal of Thrombosis and Haemostasis in 2020, which noted that a D-dimer ≥0.5 mg/L was present in 46.4% of patients with COVID-19, with higher levels associated with severe illness and mortality 1. The study also highlighted that patients with markedly raised D-dimers, defined as a three- to four-fold increase, should be considered for hospital admission due to the increased risk of thrombotic complications.
The clinical significance of elevated D-dimer levels is further supported by the 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism, which state that D-dimer testing has a high negative predictive value, but a low positive predictive value due to its elevation in various conditions such as cancer, infection, and inflammation 1. Additionally, the ACR Appropriateness Criteria for acute chest pain-suspected pulmonary embolism emphasize the importance of considering clinical and laboratory evidence, including D-dimer levels, in the diagnostic workup of patients with suspected pulmonary embolism 1.
In terms of management, patients with elevated D-dimer levels should undergo further diagnostic testing, such as imaging studies, to determine the underlying cause of the elevation. The specific follow-up depends on the patient's clinical presentation and risk factors, and may include monitoring for worsening symptoms such as increasing leg pain/swelling, chest pain, or shortness of breath, which would warrant immediate medical attention. It is also important to note that the threshold for what is considered an elevated D-dimer level may be adjusted based on age, with some studies suggesting that an age-adjusted threshold (age × 10 μg/L for patients over 50) may improve specificity 1.
Key points to consider in the management of patients with elevated D-dimer levels include:
- The need for further diagnostic testing to determine the underlying cause of the elevation
- The importance of considering clinical and laboratory evidence, including D-dimer levels, in the diagnostic workup
- The potential for elevated D-dimer levels to be associated with increased thrombin generation and potential mortality, particularly in patients with COVID-19
- The need for hospital admission in patients with markedly raised D-dimer levels, even in the absence of other severe symptoms.
From the Research
Elevated D Dimer Levels
Elevated D dimer levels are a marker of coagulation and fibrinolytic system activation, and can be an indicator of serious underlying disease, including venous thromboembolism (VTE), sepsis, and cancer 2.
Causes of Elevated D Dimer Levels
Some of the causes of elevated D dimer levels include:
- Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism 3, 4
- Sepsis 2
- Cancer 2
- Trauma or surgery 2
- COVID-19 3
Diagnosis and Management
D dimer testing is often used in the diagnosis and management of thrombotic and bleeding disorders, including VTE 3, 5. However, the test has limitations, including low specificity and potential for diagnostic errors 6.
Clinical Implications
Extremely elevated D dimer levels (> 5000 μg/l) are uniquely associated with severe disease, mainly including VTE, sepsis, and/or cancer 2. Therefore, even if sharply elevated D dimers are a seemingly solitary finding, clinical suspicion of severe underlying disease should be maintained.
D Dimer Assays
D dimer assays can be used to predict clinical severity of COVID-19 and to identify patients who may benefit from prolonged anticoagulation 3. However, assay standardization remains problematic, and clinicians need to be aware of variability in D dimer assay performance and the characteristics of their institution's test when making clinical decisions 5.