What are the causes of an elevated D-dimer (D-dimer)

From the Guidelines

D-dimer can be elevated due to numerous conditions beyond just blood clots, including deep vein thrombosis (DVT), pulmonary embolism (PE), disseminated intravascular coagulation (DIC), pregnancy, advancing age, surgery or trauma, cancer, infections or inflammation, liver disease, heart failure, COVID-19 infection, and certain medications like oral contraceptives. The most common causes of elevated d-dimer levels are:

• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Disseminated intravascular coagulation (DIC)
• Pregnancy
• Advancing age
• Surgery or trauma
• Cancer
• Infections or inflammation
• Liver disease
• Heart failure
• Recent COVID-19 infection
• Certain medications like oral contraceptives
• Stroke
• Myocardial infarction
• Aortic dissection
• Vasculitis
• Prolonged immobility or long flights 1. This wide range of potential causes explains why d-dimer is considered highly sensitive but not specific for blood clots. The test works by detecting fibrin degradation products that form when blood clots break down, which occurs in many clinical scenarios beyond thrombosis. This is why positive d-dimer results typically require follow-up testing like ultrasound or CT scans to confirm the specific underlying cause. It is essential to consider the clinical context and use d-dimer testing in conjunction with other diagnostic tools to accurately diagnose the underlying condition 1. In patients with suspected acute pulmonary embolism, d-dimer testing can be used as an initial step, but it is crucial to consider the pretest probability and use a combination of clinical risk stratification and imaging studies to confirm the diagnosis 1. The Pulmonary Embolism Rule-Out Criteria (PERC) can be used to guide clinicians in identifying low-risk patients in whom the risks of any testing, including a plasma d-dimer level, outweigh the risk for PE 1. Overall, elevated d-dimer levels should be interpreted with caution, and a comprehensive diagnostic approach should be taken to determine the underlying cause.

From the Research

Causes of Elevated D-Dimer

• Venous thromboembolism (VTE) 2, 3, 4
• Sepsis 2, 3
• Cancer 2, 3, 5
• Trauma/surgery 2
• Deep vein thrombosis (DVT) 2, 6, 4
• Pulmonary embolism (PE) 2, 6, 4
• Disseminated intravascular coagulation (DIC) 6
• Infectious diseases 5
• Physiologic conditions, including:
  • Aging 5
  • Pregnancy 5
  • Strenuous physical activity 5
• Intracranial hemorrhage 6
• Gastrointestinal (GI) bleed 6

Disease States Associated with Elevated D-Dimer

• Medically ill subjects with elevated D-dimer constitute a high-risk subgroup for adverse outcomes, including incident VTE, recurrent VTE, and mortality 3
• Elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states 3