What is the management approach for a patient with COVID-19 (Coronavirus Disease 2019) and elevated D-dimer (D-dimer) levels?

Management of Patients with COVID-19 and Elevated D-dimer Levels

Patients with COVID-19 and elevated D-dimer levels should receive prophylactic anticoagulation with low molecular weight heparin (LMWH) upon hospital admission, unless contraindicated, with monitoring of coagulation parameters to guide further management. 1

Assessment and Risk Stratification

• D-dimer interpretation:

  • Mild elevation (2× upper limit of normal): Increased VTE risk and poor prognosis
  • Moderate elevation (3-4× upper limit of normal): Consider hospital admission and close monitoring
  • Severe elevation (≥6× upper limit of normal): Strong predictor of thrombotic events and mortality 1
  • Critical elevation (≥5 mg/mL): Consider therapeutic anticoagulation and thorough investigation for thrombosis 1

• Initial laboratory evaluation:

  • Complete D-dimer, prothrombin time (PT), platelet count, and fibrinogen assessment 1
  • Serial monitoring of these parameters is necessary to track disease progression 2

• Important: Do not use D-dimer alone to guide anticoagulation intensity 2, 1

  • D-dimer should be interpreted alongside clinical presentation and other coagulation parameters

Anticoagulation Protocol

For Non-ICU Hospitalized COVID-19 Patients:

• Standard prophylactic anticoagulation:
  • LMWH (preferred): Enoxaparin 40 mg daily 2, 1
  • Alternative: UFH twice or thrice daily if LMWH contraindicated 2
  • Consider intermediate-dose LMWH in selected high-risk patients 2

For ICU Hospitalized COVID-19 Patients:

• Consider intensified prophylactic dosing:
  • Enoxaparin 40 mg twice daily or heparin 7500 units three times daily 2
  • Adjust based on renal function, weight, and bleeding risk 1

Contraindications to Anticoagulation:

• Active bleeding
• Platelet count <25 × 10^9/L
• Severe renal impairment 1
• In these cases, use mechanical thromboprophylaxis (intermittent pneumatic compression devices) 2

Diagnostic Approach for Suspected VTE

• Do not perform routine screening for VTE based solely on elevated D-dimer levels 2

• Perform objective testing when clinically suspected:

  • Use standard-of-care objective testing (CTPA, V/Q scan, MRI venography, Doppler ultrasonography) 2
  • Point-of-care bedside ultrasonography or echocardiography can complement standard testing 2

• Clinical indications for VTE investigation:

  • Unexplained sudden deterioration of pulmonary status
  • Acute lower extremity erythema or swelling 2
  • D-dimer >1.5 mg/L has shown 85% sensitivity and 88.5% specificity for diagnosing VTE in COVID-19 patients 2, 3

Monitoring and Adjustment

• Serial monitoring:

  • Track D-dimer, PT, platelet count, and fibrinogen levels 1
  • Decreasing D-dimer levels suggest effective treatment
  • Persistently elevated or rising levels may indicate treatment failure or ongoing thrombosis 1

• Bleeding risk management:

  • Maintain platelet count >25 × 10^9/L in non-bleeding patients
  • Maintain platelet count >50 × 10^9/L in bleeding patients
  • Keep fibrinogen >1.5 g/L 1

Special Considerations

• Medication interactions:

  • Use caution with direct oral anticoagulants (DOACs) in COVID-19 patients receiving immunosuppressant, antiviral, or experimental therapies 2

• Weight and renal function:

  • Modify prophylaxis based on extremes of body weight
  • Adjust for severe thrombocytopenia (platelet counts <50,000 × 10^9/L)
  • Adjust for deteriorating renal function 2

Important Clinical Pitfalls

• Do not rely solely on D-dimer to guide anticoagulation decisions - this can lead to inappropriate anticoagulation intensity 2, 1

• Do not perform routine screening ultrasounds in asymptomatic COVID-19 patients - this increases unnecessary exposure to healthcare workers 4

• Do not overlook the high prevalence of PE in patients with COVID-19 pneumonia and D-dimer values >1 μg/mL (50% prevalence reported) 3

• Do not use thromboelastography (TEG) or rotational thromboelastometry (ROTEM) routinely to guide management - these are still under investigation 2

• Do not fail to adjust anticoagulation for body weight - this can lead to underdosing in obese patients and overdosing in low-weight or renally impaired patients 1