What are the causes of elevated D-dimer (D-dimer) levels, a protein fragment produced during fibrinolysis?

From the Guidelines

Elevated D-dimer levels are primarily caused by conditions that activate the coagulation system, including deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, recent surgery, trauma, malignancies, and infections, as well as inflammatory conditions like sepsis and COVID-19, as supported by recent studies 1.

Causes of Elevated D-dimer Levels

The causes of elevated D-dimer levels can be broadly categorized into several groups:

• Thrombotic disorders: deep vein thrombosis (DVT), pulmonary embolism (PE)
• Coagulation disorders: disseminated intravascular coagulation (DIC)
• Inflammatory conditions: sepsis, COVID-19, autoimmune disorders
• Trauma and surgery: recent trauma, surgery
• Malignancies: cancer
• Infections: bacterial, viral, or fungal infections
• Other conditions: pregnancy, advanced age, certain medications like oral contraceptives and hormone replacement therapy

Importance of D-dimer Measurement

D-dimer measurement is a useful tool in diagnosing and managing coagulation disorders, as it has high sensitivity but low specificity for thrombotic disorders 1. A negative D-dimer result can help rule out conditions like DVT or PE, but a positive result requires further diagnostic testing to determine the specific cause. The degree of elevation can sometimes provide clues about the underlying condition, with massive elevations often seen in DIC or severe thrombotic events.

Recent Findings

Recent studies have highlighted the importance of D-dimer measurement in patients with COVID-19, as elevated D-dimer levels have been associated with disease severity and death 1. However, the use of D-dimer assays can be limited by variability and inconsistency in their sensitivity, specificity, and reporting units, making it challenging to harmonize data from large meta-analysis-driven cohort studies.

From the Research

Causes of Elevated D-dimer Levels

Elevated D-dimer levels can be caused by various conditions, including:

• Venous thromboembolism (VTE) 2, 3, 4, 5
• Sepsis 2, 6, 5
• Cancer 2, 6, 5
• Trauma/surgery 2, 5
• Cerebrovascular accident 5
• Malignancy 6
• Infection 6
• Arrhythmias 6
• Deep vein thrombosis (DVT) 2, 4
• Pulmonary embolism (PE) 2, 4
• Disseminated intravascular coagulation (DIC) 4

Association with Adverse Outcomes

Elevated D-dimer levels have been associated with adverse outcomes, including:

• Increased risk of incident VTE 3
• Recurrent VTE 3
• Mortality 3, 6, 5
• Underlying malignancy 6

Diagnostic Value

D-dimer levels can be used as a diagnostic tool to:

• Rule out VTE in patients with low clinical probability 4
• Identify patients with high risk of thrombosis 4
• Detect coagulopathy in emergency patients 5
• Distinguish between different diagnoses, such as VTE and sepsis 5