What to do if fibrinogen levels are elevated?

Management of Elevated Fibrinogen Levels

When fibrinogen levels are elevated, the primary approach should be to identify and treat the underlying cause rather than directly targeting the elevated fibrinogen itself, while monitoring for potential thrombotic complications. 1

Understanding Elevated Fibrinogen

Elevated fibrinogen (hyperfibrinogenemia) is often a marker of:

• Inflammatory conditions
• Acute phase reactions
• Cardiovascular risk
• Potential thrombotic predisposition

Clinical Significance

• Fibrinogen is both a marker of inflammation and a major determinant in thrombosis 2
• Even minimal increases in fibrinogen levels within reference ranges can indicate significantly increased cardiovascular risk 2
• High fibrinogen levels are associated with thrombotic complications, though the underlying causative mechanisms likely involve associated inflammatory and hypercoagulable states 3

Diagnostic Approach

1. Confirm elevation with repeat testing if initial result is unexpected

2. Evaluate for underlying causes:

   • Acute inflammation or infection
   • Chronic inflammatory conditions
   • Malignancy
   • Pregnancy
   • Liver disease
   • Genetic variants (dysfibrinogenemia)

3. Consider additional testing:

   • Complete blood count with differential
   • C-reactive protein and ESR
   • Liver function tests
   • Viscoelastic testing (TEG/ROTEM) if available to assess functional clot formation 1

Management Strategy

1. Address Underlying Causes

• Treat infections with appropriate antimicrobials
• Manage inflammatory conditions with appropriate anti-inflammatory therapy
• Address any malignancy according to oncology guidelines
• Control cardiovascular risk factors

2. Risk Assessment for Thrombosis

• Evaluate for additional thrombotic risk factors
• Consider thromboprophylaxis in high-risk patients (e.g., hospitalized, immobilized, or post-surgical)
• For patients with dysfibrinogenemia type 3B (thrombotic phenotype), thromboprophylaxis should be administered 4

3. Monitoring Recommendations

• Regular follow-up of fibrinogen levels until normalized
• Monitor for signs and symptoms of thrombosis
• In pregnancy with elevated fibrinogen, quarterly assessment of fibrinogen activity level and antigen level is recommended 4

4. Specific Clinical Scenarios

Elevated Fibrinogen in Bleeding Patients

• Focus on addressing the cause of bleeding rather than the elevated fibrinogen 1

• Elevated fibrinogen in a bleeding patient suggests:

  • Bleeding is not yet severe enough to deplete fibrinogen reserves
  • Pre-existing inflammatory condition causing hyperfibrinogenemia
  • Possible qualitative fibrinogen dysfunction despite adequate quantity 1

• Use viscoelastic monitoring (TEG/ROTEM) to guide resuscitation measures, focusing on functional assessment of clot formation rather than absolute fibrinogen levels 4, 1

Pregnancy and Delivery

• In women with dysfibrinogenemia, fibrinogen replacement is not routinely recommended during pregnancy 4
• For vaginal bleeding during pregnancy, fibrinogen replacement should target a level ≥1.5 g/L until bleeding stops 4
• During labor and delivery, maintain fibrinogen level ≥1.5 g/L in women with a bleeding phenotype 4

Cardiac Surgery

• Monitor plasma fibrinogen level in bleeding patients 4
• Consider viscoelastic tests instead of Clauss assay for estimating fibrinogen's contribution to clot formation 4
• In cardiac surgery patients with continuous, significant microvascular bleeding:
  • Strongly recommended to replace fibrinogen if levels are very low (≤4-6 mm MCF in FIBTEM)
  • Consider replacement if borderline levels (6-8 mm MCF in FIBTEM)
  • Target maintenance of physiological levels (>9 mm MCF in FIBTEM) but avoid very high levels (>14 mm MCF) 4

Therapeutic Considerations

Lifestyle Modifications

• Smoking cessation is the most effective lifestyle change to lower fibrinogen 5
• Weight reduction, stress management, and increased physical activity may have modest effects 5
• Regular, moderate alcohol consumption may result in small reductions 5

Pharmacological Interventions

• No medications are specifically indicated solely to lower fibrinogen levels
• Some medications may have fibrinogen-lowering effects as secondary benefits:
  • Fibrates (e.g., bezafibrate) may reduce elevated fibrinogen by up to 40% 5
  • Ticlopidine can induce a reduction of about 15% if fibrinogen was elevated at baseline 5

Important Caveats

• Fibrinogen appears to be more of a marker than a mediator of vascular disease, making selective fibrinogen lowering potentially less useful as a preventive strategy 6
• Post-traumatic fibrinogen levels naturally rise to approximately 7 g/L after major trauma 4
• Balance any hemostatic therapy against risk of thrombosis 1
• Genetic polymorphisms in the fibrinogen gene with higher fibrinogen levels do not necessarily increase the risk for myocardial infarction 6

Pitfalls to Avoid

• Don't focus exclusively on lowering fibrinogen without addressing the underlying cause
• Avoid overreliance on plasma fibrinogen levels without considering functional assessment
• Don't initiate anticoagulation based solely on elevated fibrinogen without other indications
• Remember that laboratory methods to measure fibrinogen concentration have methodological issues and may be affected by artificial colloids 4