What is the frequency of a normal D-dimer (Deep Vein Thrombosis screening test) in patients with evidence of Deep Vein Thrombosis (DVT) on ultrasound?

From the Guidelines

D-dimer tests can come back normal in approximately 5% of patients who have evidence of deep vein thrombosis (DVT) on ultrasound, as suggested by a prospective cohort study 1. This means that while D-dimer is a useful screening tool, it is not 100% sensitive for DVT. For patients with suspected DVT, it's essential to use a combination of clinical assessment, D-dimer testing, and imaging studies like ultrasound. Even if the D-dimer is negative, if clinical suspicion is high or ultrasound shows evidence of DVT, treatment should be initiated. Some key points to consider:

• D-dimer levels appear to return to normal values within 3 months of starting treatment of acute DVT, and remain within the normal range after anticoagulant therapy is withdrawn in the majority of patients 1.
• A negative sensitive D-dimer was used either in combination with an unlikely pretest probability using the modified Wells model or a CUS at presentation that was either normal or showed an increase in residual diameter of < 4 mm to exclude recurrence, with no patients experiencing VTE during 3 months of follow-up 1.
• The combination of an unlikely pretest probability and negative D-dimer had a frequency of VTE during 3-month follow-up of 0.9% (95% CI, 0.3%-3.3%) in a randomized trial of 1,096 outpatients with suspected DVT 1. The standard treatment for DVT typically involves anticoagulation:

• Initial treatment: Low molecular weight heparin (e.g., enoxaparin 1 mg/kg twice daily) or direct oral anticoagulants (e.g., rivaroxaban 15 mg twice daily for 21 days, then 20 mg once daily)
• Duration: At least 3 months, with reassessment for longer-term needs D-dimer can be normal in DVT cases due to several factors:

1. Small clot size
2. Chronic rather than acute DVT
3. Delayed testing after symptom onset
4. Individual variations in fibrinolysis Given these limitations, clinicians should not rely solely on D-dimer results when DVT is strongly suspected. A negative D-dimer should be interpreted in conjunction with clinical probability and imaging results for accurate diagnosis and management, as supported by the American College of Chest Physicians evidence-based clinical practice guidelines 1.

From the Research

D-dimer Frequency in Deep Vein Thrombosis (DVT) Patients

• The frequency of a normal D-dimer in patients with evidence of DVT on ultrasound is not directly stated in the provided studies.
• However, the studies provide information on the sensitivity and specificity of D-dimer assays in diagnosing DVT, which can be used to estimate the frequency of normal D-dimer levels in DVT patients.
• According to 2, the sensitivity of D-dimer for the diagnosis of DVT was 97.9%, which means that approximately 2.1% of DVT patients may have a normal D-dimer level.
• Another study 3 found that initial D-dimer levels were elevated in 92.7% of patients with DVT, suggesting that around 7.3% of DVT patients may have a normal D-dimer level.
• A study published in 4 reported a sensitivity of 97.7% for D-dimer assay in diagnosing DVT, which implies that about 2.3% of DVT patients may have a normal D-dimer level.

D-dimer Levels in DVT Patients

• The studies also provide information on the D-dimer levels in patients with DVT.
• According to 3, initial D-dimer levels were associated with thrombus extent, and levels of 2000 ng/mL or greater were predictive of recurrent events.
• A study published in 5 found that the median D-dimer level in DVT-unlikely patients with positive ultrasound for DVT was significantly higher than in those with negative ultrasound results (2208 vs. 921 ng/ml FEU).
• The optimal D-dimer cut-off level for diagnosing DVT was found to be 1251 ng/ml FEU, with a sensitivity of 80% and specificity of 66.67% 5.

Ultrasound Diagnosis of DVT

• The studies highlight the importance of ultrasound in diagnosing DVT, particularly in patients with suspected recurrent DVT.
• According to 2, a diagnostic strategy combining clinical evaluation and D-dimer has proved to be useful for the exclusion of DVT in subjects with clinically suspected recurrent DVT.
• A study published in 6 found that both rapid and complete compression ultrasound (CUS) examinations are safe and efficient diagnostic strategies for DVT, with differing advantages and disadvantages.
• Another study 5 suggested that limiting proximal or thigh vein ultrasound examinations in preoperative patients with a low clinical probability of DVT may help minimize unnecessary complete venous ultrasound lower-extremity examinations.