What is the risk of thrombosis in patients with elevated fibrinogen and normal D-dimer (D-dimer) levels?

Risk of Thrombosis with Elevated Fibrinogen and Normal D-dimer

Elevated fibrinogen with normal D-dimer alone does not warrant anticoagulation therapy, but should prompt further clinical risk assessment for thrombosis using validated tools like Wells score or Geneva score.

Understanding the Clinical Significance

Fibrinogen is a key component in the coagulation cascade that can contribute to thrombosis risk through various mechanisms. While elevated fibrinogen levels are associated with thrombotic complications, this association is complex and likely involves inflammatory and hypercoagulable states 1.

When evaluating thrombosis risk:

• D-dimer is widely used as a biomarker for active thrombosis, with high sensitivity but poor specificity
• Fibrinogen elevation without D-dimer elevation presents a clinical dilemma
• Multiple guidelines recommend against using isolated biomarkers to guide anticoagulation decisions

Risk Assessment Algorithm

1. Initial Biomarker Evaluation:

   • Elevated fibrinogen with normal D-dimer requires clinical context assessment
   • Do not initiate anticoagulation based solely on fibrinogen levels 2, 3

2. Clinical Risk Stratification:

   • Apply validated VTE risk assessment tools (Wells score, Geneva score) 2, 3
   • Assess for additional VTE risk factors:
     • Immobility
     • Obesity
     • History of VTE
     • Active cancer
     • Recent surgery
     • Advanced age

3. Decision Making Based on Risk Level:

   • Low clinical risk + elevated fibrinogen + normal D-dimer:

     • Clinical monitoring without anticoagulation
     • Consider mechanical prophylaxis if other minor risk factors present

   • Moderate/high clinical risk + elevated fibrinogen + normal D-dimer:

     • Consider imaging studies regardless of D-dimer 3
     • If imaging negative: standard prophylactic anticoagulation may be considered
     • If imaging positive: therapeutic anticoagulation

Special Considerations

COVID-19 Context

In COVID-19 patients, elevated fibrinogen with normal D-dimer requires special attention:

• COVID-19 creates a hypercoagulable state with endotheliopathy 4
• The ASH guideline panel suggests using prophylactic-intensity anticoagulation for COVID-19 patients with acute illness 2
• For critically ill COVID-19 patients, prophylactic-intensity over intermediate or therapeutic-intensity anticoagulation is recommended 2

Non-COVID Hospitalized Patients

For acutely ill hospitalized patients without COVID-19:

• Standard prophylactic anticoagulation with LMWH is recommended based on overall VTE risk assessment, not solely on fibrinogen levels 2, 3
• Fibrinogen >500 mg/dL has been associated with increased thrombotic risk (OR 6.19) in some studies 5

Common Pitfalls to Avoid

1. Using fibrinogen as sole decision-maker: Fibrinogen should not be used in isolation to guide anticoagulation decisions 2, 3

2. Ignoring clinical context: Elevated fibrinogen occurs in many conditions including inflammation, infection, and pregnancy

3. Overlooking other risk factors: Even with normal D-dimer, patients with multiple clinical risk factors may benefit from thromboprophylaxis

4. Failing to consider bleeding risk: Always balance thrombotic risk against bleeding risk when considering anticoagulation

Conclusion

Elevated fibrinogen with normal D-dimer represents a moderate risk factor for thrombosis that should trigger comprehensive clinical risk assessment rather than automatic anticoagulation. The decision to anticoagulate should be based on validated risk assessment tools and overall clinical picture, not solely on biomarker levels.