What are the causes of an elevated D-dimer (D-dimer) level, indicating hypercoagulability or thrombosis?

From the Guidelines

Elevated D-dimer levels can be caused by various conditions, including deep vein thrombosis (DVT), pulmonary embolism (PE), disseminated intravascular coagulation (DIC), recent surgery, pregnancy, cancer, severe infections, and heart attacks, as well as inflammatory conditions like COVID-19, rheumatoid arthritis, and systemic lupus erythematosus 1. The most recent and highest quality study, published in 2020, highlights the importance of considering D-dimer levels in the context of venous thromboembolism treatment and management 1. Some key points to consider when evaluating elevated D-dimer levels include:

• D-dimer is a fibrin degradation product formed when the body breaks down blood clots, which explains why any condition involving clot formation or significant inflammation can lead to elevated levels 1.
• Advanced age naturally increases baseline D-dimer values, and even minor injuries, bruising, or recent vaccinations may cause temporary elevations 1.
• While a normal D-dimer can help rule out thrombotic conditions, an elevated result requires further investigation to determine the specific cause, as it lacks specificity on its own 1.
• Inflammatory conditions, such as COVID-19, rheumatoid arthritis, and systemic lupus erythematosus, can also raise D-dimer levels, making it essential to consider the patient's overall clinical presentation and medical history when interpreting D-dimer results 1.
• The American Society of Hematology 2020 guidelines for management of venous thromboembolism emphasize the importance of considering D-dimer levels in the context of treatment and management of deep vein thrombosis and pulmonary embolism 1.

From the Research

Causes of Elevated D-Dimer

• Venous thromboembolism (VTE) is a major cause of elevated D-dimer levels, with pulmonary embolism and deep vein thrombosis being the most common conditions 2, 3, 4, 5
• Sepsis is another significant cause of elevated D-dimer levels, with a high prevalence among patients with extremely elevated D-dimer results 2
• Cancer is also a common cause of elevated D-dimer levels, with various types of cancer associated with an increased risk of VTE and subsequent elevation of D-dimer levels 2, 3, 4
• Trauma and surgery can also lead to elevated D-dimer levels, due to tissue injury and the resulting inflammatory response 6
• Other conditions, such as infection and inflammation, can also cause elevated D-dimer levels, although the evidence is less clear-cut 2

Mechanisms of D-Dimer Elevation

• Tissue injury and inflammation can lead to the activation of coagulation pathways, resulting in the formation of fibrin and subsequent elevation of D-dimer levels 6
• Cancer can lead to the activation of coagulation pathways, resulting in the formation of thrombi and subsequent elevation of D-dimer levels 2, 3, 4
• Sepsis can lead to the activation of coagulation pathways, resulting in the formation of thrombi and subsequent elevation of D-dimer levels 2

Clinical Implications

• Elevated D-dimer levels can be used as a diagnostic tool to rule out VTE, but extremely elevated levels may indicate a more severe underlying condition 2, 3, 4, 5
• The use of D-dimer testing in patients with trauma or surgery may be limited, due to the potential for false positives and the lack of a clear trend for gradual decrease to normal within the first three days after trauma 6
• Anticoagulation therapy may be indicated in patients with elevated D-dimer levels, particularly those with VTE or cancer, to prevent progression and reduce the risk of post-thrombotic syndrome and pulmonary embolism 3, 4, 5