Are D-dimer (D-dimer) levels elevated in patients with sickle cell disease (SCD)?

D-Dimer Levels in Sickle Cell Disease

D-dimer levels are significantly elevated in patients with sickle cell disease, both during the steady state and particularly during vaso-occlusive crises. This elevation reflects ongoing activation of coagulation and fibrinolysis in these patients, which is a characteristic feature of the disease.

Evidence for Elevated D-dimer in Sickle Cell Disease

The evidence strongly supports elevated D-dimer levels in sickle cell patients:

• Studies show that 97% of patients with sickle cell disease during vaso-occlusive crisis have positive D-dimer tests (>1 μg/ml) 1
• Even in the asymptomatic "steady state," 23 out of 25 sickle cell patients (92%) demonstrated elevated D-dimer levels 2
• Mean D-dimer levels are significantly higher in sickle cell patients compared to normal subjects:
  • Normal subjects: 79 ± 25 ng/ml
  • Sickle cell patients in steady state: 566 ± 739 ng/ml
  • Sickle cell patients during painful crisis: 1,038 ± 1,010 ng/ml 2

Clinical Significance of Elevated D-dimer in Sickle Cell Disease

The elevated D-dimer levels in sickle cell disease have several important clinical implications:

1. Diagnostic marker: D-dimer can serve as an objective marker for vaso-occlusive crisis and other complications of sickle cell disease 1

2. Correlation with disease activity:

   • Serial measurements show that worsening or improvement in clinical complications are reflected by increasing or decreasing D-dimer levels 1
   • D-dimer levels are higher during painful crises compared to steady state 2

3. Correlation with chest abnormalities:

   • A normal D-dimer level has a high negative predictive value (92.9%) for abnormal chest X-ray findings in sickle cell patients 3

4. Response to anticoagulation therapy:

   • Low-dose warfarin significantly reduces D-dimer levels during vaso-occlusive crisis (median 0.81 μg FEU/mL with warfarin vs. 3.1 μg FEU/mL without) 4

Mechanism of D-dimer Elevation in Sickle Cell Disease

The elevated D-dimer levels in sickle cell disease reflect:

• Increased thrombin activity and fibrin formation as features of the disease 2
• Ongoing activation of coagulation and secondary fibrinolysis
• Microvascular occlusion leading to local thrombosis and subsequent fibrinolysis

Clinical Application

When interpreting D-dimer levels in sickle cell patients:

• Expect elevated levels even in asymptomatic patients
• Higher levels during vaso-occlusive crisis may help confirm the diagnosis
• Normal levels during suspected crisis may suggest alternative diagnoses
• Serial measurements may help monitor disease activity and response to treatment

Caution in Interpretation

While D-dimer is elevated in sickle cell disease, it's important to note that D-dimer elevation is not specific and can be found in many conditions including:

• Pregnancy 5
• Inflammatory states
• Malignancy
• Liver disease
• Acute infections
• Venous thromboembolism 6

Therefore, D-dimer elevation in sickle cell patients should be interpreted in the context of their clinical presentation and other laboratory findings.