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 or sepsis, heart attack, stroke, and severe trauma or burns, as well as inflammatory conditions and certain medications, with the most recent evidence suggesting that COVID-19 can also lead to elevated D-dimer levels 1.
Causes of Elevated D-dimer
The causes of elevated D-dimer levels can be categorized into several groups, including:
- Thrombotic conditions, such as DVT and PE, which are associated with the formation of blood clots in the deep veins or lungs, respectively 1
- Inflammatory conditions, such as rheumatoid arthritis and systemic lupus erythematosus, which can lead to increased clotting activity and elevated D-dimer levels
- Infectious conditions, such as severe infections or sepsis, which can cause disseminated intravascular coagulation (DIC) and elevated D-dimer levels 1
- Traumatic conditions, such as severe trauma or burns, which can lead to increased clotting activity and elevated D-dimer levels
- Medications, such as oral contraceptives, which can contribute to elevated D-dimer levels
- Age-related increases, which can occur naturally with rising age
- COVID-19, which has been shown to lead to elevated D-dimer levels, particularly in severe cases 1
Clinical Significance
Elevated D-dimer levels are not specific to any particular condition and can be caused by a variety of factors. However, a negative D-dimer test can be useful in ruling out conditions such as DVT or PE, particularly in low-risk patients 1. On the other hand, a positive D-dimer test requires further evaluation to determine the underlying cause of the elevated levels.
Management
The management of elevated D-dimer levels depends on the underlying cause and may involve anticoagulation therapy, treatment of the underlying condition, or further evaluation to determine the cause of the elevated levels. In patients with COVID-19, elevated D-dimer levels may indicate increased thrombin generation and require admission to hospital for further management 1.
From the Research
Causes of Elevated D-Dimer
- Elevated D-dimer levels can be caused by various conditions, including:
- It is essential to note that D-dimer levels can be elevated in several other conditions, and the test has low specificity 3, 4
- The diagnostic accuracy of D-dimer levels can be improved by adjusting the cutoffs according to patient characteristics, such as age, pretest probability, pregnancy, renal function, or cancer 4
Conditions Associated with Elevated D-Dimer
- Pulmonary embolism: D-dimer testing can be used to rule out PE, especially when combined with a clinical pretest probability assessment 2, 5, 6
- Deep vein thrombosis: D-dimer testing can be used to rule out DVT, especially when combined with a clinical pretest probability assessment 2, 5
- Sepsis: Elevated D-dimer levels can be associated with sepsis, and the test can be used as a marker of coagulation and fibrinolytic system activation 2
- Cancer: Elevated D-dimer levels can be associated with cancer, especially in patients with a high pretest probability 2, 4
Interpretation of D-Dimer Results
- D-dimer results should be interpreted with caution, taking into account the patient's clinical presentation, pretest probability, and other laboratory results 3, 6
- The intended use of the D-dimer test depends largely on the assay used, and local guidance should be applied 6
- Diagnostic errors can occur throughout the pre-analytical, analytical, and post-analytical phases of the testing process, and it is essential to be aware of these potential pitfalls 6