What are the causes of elevated D-dimer (D-dimer) levels?

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 vasculitis. The most recent and highest quality study, published in 2020 in the Journal of Thrombosis and Haemostasis 1, highlights the significance of D-dimer elevation in COVID-19 patients, where markedly elevated D-dimers were identified as one of the predictors of mortality.

Conditions Associated with Elevated D-dimer

• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Disseminated intravascular coagulation (DIC)
• Recent surgery
• Pregnancy
• Cancer
• Severe infections
• Heart attacks
• Inflammatory conditions like COVID-19, rheumatoid arthritis, and vasculitis

According to the 2020 study in the European Heart Journal 1, D-dimer levels are also elevated in patients with cancer, hospitalized patients, severe infection or inflammatory disease, and during pregnancy. The study notes that the number of patients in whom D-dimer must be measured to exclude one PE (number needed to test) rises from 3 in the general population of an emergency department to >10 in specific situations like cancer, hospitalization, or pregnancy.

Clinical Implications

The elevation of D-dimer levels indicates active clotting and fibrinolysis, but due to its low specificity for thrombotic disorders, it is more useful for ruling out conditions like DVT or PE when levels are normal rather than confirming their presence when elevated, as stated in the 2010 guidelines published in Circulation 1. Therefore, a negative D-dimer result can be useful in ruling out thrombotic disorders in low-risk patients, but a positive result should be interpreted with caution and considered in the context of the patient's overall clinical presentation.

From the Research

Causes of Elevated D-Dimer

• Elevated D-dimer levels are associated with various conditions, including:
  • Venous thromboembolism (VTE) 2, 3, 4
  • Sepsis 2
  • Cancer 2
  • Trauma/surgery 2
  • Deep vein thrombosis (DVT) 5, 3, 4
  • Pulmonary embolism (PE) 5, 3, 6, 4
  • Disseminated intravascular coagulation (DIC) 5
• A study found that 89% of patients with extremely elevated D-dimer levels (> 5000 μg/l) had a diagnosis of VTE, sepsis, and/or cancer 2
• Elevated plasma D-dimer levels are also associated with an increased risk of future incident VTE, with participants in the highest quartile of D-dimer levels having an odds ratio of 1.65 for VTE compared to those in the lowest quartile 4

Conditions Associated with Elevated D-Dimer

• The conditions associated with elevated D-dimer levels can be categorized into:
  • Thrombotic disorders: VTE, DVT, PE, DIC 2, 5, 3, 4
  • Inflammatory conditions: sepsis, cancer 2
  • Traumatic conditions: trauma/surgery 2
• It is essential to consider these conditions when interpreting elevated D-dimer levels, as they may indicate a severe underlying disease 2