Causes of Elevated D-dimer and Required Follow-up
When a patient presents with an elevated D-dimer level, a systematic evaluation for venous thromboembolism (VTE) should be performed first, followed by investigation of other potential causes if VTE is ruled out. 1, 2
Primary Evaluation for VTE
- For patients with elevated D-dimer, initial evaluation should focus on ruling out deep vein thrombosis (DVT) and pulmonary embolism (PE) as these represent the most common serious conditions associated with elevated D-dimer 1, 2
- Compression ultrasonography (CUS) of the lower extremities is recommended as the first-line test for suspected DVT 1
- If proximal CUS is positive in patients with suspected DVT, treatment should be initiated without further confirmatory testing 1
- For suspected PE, CT pulmonary angiography (CTPA) is the recommended imaging modality 1, 2
Other Causes of Elevated D-dimer
If VTE has been ruled out, the following conditions should be investigated:
Inflammatory and Infectious Conditions
- Sepsis and disseminated intravascular coagulation (DIC) 3, 4
- COVID-19 and other severe infections (elevated D-dimer in COVID-19 correlates with disease severity) 1
Cardiovascular Conditions
- Acute aortic dissection (D-dimer has high sensitivity but variable specificity) 2
- Chronic heart failure (can create a hypercoagulable state) 5
- Post-cardiopulmonary resuscitation status 3
Hematologic/Vascular Conditions
- Active cancer (particularly metastatic or those receiving chemotherapy) 4
- Recent surgery or trauma 4
- Massive bleeding from any source 3
Pregnancy-Related Conditions
- Normal pregnancy (D-dimer levels physiologically increase throughout pregnancy) 1
- HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) 3
Other Conditions
- Advanced age (D-dimer levels increase with age) 6
- Laboratory interference from heterophilic antibodies (can cause falsely elevated results) 5
Required Follow-up
For Confirmed VTE
- Initiate appropriate anticoagulation therapy 1
- For isolated distal DVT detected on whole-leg ultrasound, consider serial testing to rule out proximal extension 1
For Non-VTE Causes
- If sepsis or DIC is suspected: complete blood count, coagulation studies, and appropriate cultures 1, 3
- If aortic dissection is suspected: proceed directly to definitive imaging (CT angiography, MRI, or transesophageal echocardiography) 2
- If cancer is suspected: age-appropriate cancer screening and additional imaging as indicated 4
- For extremely elevated D-dimer levels (>10× upper limit of normal): thorough evaluation for VTE, sepsis, and/or malignancy is warranted as these account for 89% of such cases 4
Monitoring Recommendations
- Serial D-dimer measurements may be useful to monitor disease progression or response to therapy in certain conditions like COVID-19 1
- Be aware of D-dimer assay variability - results from different manufacturers are not directly comparable 1
- D-dimer should not be used as the sole guide for anticoagulation management decisions 1
Special Considerations
- In patients with comorbid conditions likely to cause elevated D-dimer even in the absence of VTE, initial testing with ultrasonography may be preferred over D-dimer testing 1
- For suspected upper extremity DVT with negative initial ultrasound but high clinical suspicion, consider further testing with D-dimer, serial ultrasound, or venographic-based imaging 1
- Extremely elevated D-dimer levels (>50 mg/L FEU) should prompt immediate and thorough investigation as they are highly specific for serious illness 3, 4