In a patient with sepsis and elevated fibrinogen, how should the fibrinogen level and overall management be addressed?

Elevated Fibrinogen in Sepsis: Clinical Significance and Management

In septic patients with elevated fibrinogen, the fibrinogen level itself does not require specific correction or treatment, as hypofibrinogenemia is uncommon in sepsis-associated coagulopathy and elevated fibrinogen is an expected acute phase response. 1, 2

Understanding Fibrinogen Dynamics in Sepsis

Elevated fibrinogen in sepsis represents an acute phase reaction and is not a therapeutic target. The key pathophysiologic distinction is that sepsis-associated coagulopathy is characterized by:

• Suppression of fibrinolysis due to overproduction of plasminogen activator inhibitor-1, rather than consumptive coagulopathy 1
• Hypofibrinogenemia is uncommon in sepsis, unlike malignancy-associated DIC where fibrinolytic phenotype predominates 1, 2
• Fibrinogen elevation does not correlate with sepsis severity, whereas platelet decline and PT prolongation do correlate with mortality 1

Critical Caveat: Decreasing Fibrinogen Signals Poor Prognosis

If fibrinogen levels are decreasing during ICU stay, this indicates progression to overt DIC and is associated with significantly higher mortality (46.7% vs 10.0% in patients with stable fibrinogen), even in non-overt DIC 3. This requires:

• Serial monitoring of fibrinogen trends, not just absolute values 3
• Assessment for progression to overt DIC using ISTH criteria 2
• Heightened vigilance for platelet decline, which accompanies decreasing fibrinogen 3

Diagnostic Approach: Two-Step Strategy

The ISTH recommends a two-step diagnostic approach: first assess for Sepsis-Induced Coagulopathy (SIC), then if criteria are met, assess for overt DIC. 1

Step 1: SIC Scoring (≥4 points indicates SIC)

• Platelet count: <100 × 10⁹/L = 2 points; 100-150 × 10⁹/L = 1 point 2
• PT ratio: >1.4 = 2 points; 1.2-1.4 = 1 point 2
• SOFA score: ≥2 = 2 points; 1 = 1 point 2

Note: Fibrinogen is deliberately excluded from SIC criteria because it typically remains normal or elevated in sepsis 1

Step 2: If SIC Present, Assess for Overt DIC (≥5 points indicates overt DIC)

• Platelet count: <50 × 10⁹/L = 2 points; 50-100 × 10⁹/L = 1 point 2
• Fibrin markers (D-dimer/FDP): Strong increase = 3 points; moderate increase = 2 points 2
• PT prolongation: ≥6 seconds or ratio >1.4 = 2 points; 3-6 seconds or ratio 1.2-1.4 = 1 point 2
• Fibrinogen: <100 mg/dL = 1 point 2

Management: Focus on Underlying Sepsis, Not Coagulation Parameters

Do not attempt to correct elevated fibrinogen or other coagulation abnormalities unless the patient has active bleeding or requires invasive procedures. 1, 4

Fresh Frozen Plasma (FFP)

• Do NOT use FFP to correct laboratory coagulation abnormalities in non-bleeding patients 1, 4
• FFP transfusion typically fails to correct PT in non-bleeding patients with mild abnormalities 4
• Use FFP only for: Active hemorrhage with documented coagulation factor deficiency OR immediately before planned invasive procedures/surgery 4

Antithrombin

• Do NOT administer antithrombin for treatment of septic shock 1, 4
• The KyberSept Phase III trial showed no mortality benefit and increased bleeding risk when combined with heparin 1
• This recommendation stands regardless of measured antithrombin levels 4

Platelet Transfusion Thresholds

Transfuse platelets based on these evidence-based thresholds: 1, 4

• <10,000/mm³: Prophylactic transfusion in absence of bleeding
• <20,000/mm³: If significant bleeding risk exists
• ≥50,000/mm³: For active bleeding, surgery, or invasive procedures

Fibrinogen Replacement

Only replace fibrinogen if: 2

• Fibrinogen <1.5 g/L (150 mg/dL) persists despite FFP
• AND patient has active bleeding
• Use cryoprecipitate or fibrinogen concentrate

Clinical Algorithm for Management

1. Confirm sepsis diagnosis and initiate standard sepsis management per Surviving Sepsis Campaign guidelines 4

2. Calculate SIC score using platelet count, PT ratio, and SOFA score 1, 2

3. If SIC ≥4 points: Calculate overt DIC score 2

4. Monitor fibrinogen trends serially - decreasing levels indicate poor prognosis and progression to overt DIC 3

5. Assess for active bleeding:

   • If NO bleeding: Do not correct coagulation abnormalities; focus on treating underlying sepsis 4
   • If YES bleeding: Use FFP for factor deficiency, platelets per thresholds above, fibrinogen replacement only if <150 mg/dL despite FFP 4, 2

6. Before invasive procedures: Consider FFP if significant PT prolongation; ensure platelets ≥50,000/mm³ 4

7. Avoid antithrombin therapy regardless of levels 1, 4

Key Pitfalls to Avoid

• Do not treat elevated fibrinogen - it is an expected acute phase reactant, not a therapeutic target 1, 2
• Do not use fibrinogen level alone to assess DIC severity in sepsis - it is deliberately excluded from SIC criteria 1
• Do not ignore decreasing fibrinogen trends - this signals progression to overt DIC with high mortality 3
• Do not transfuse FFP prophylactically to "normalize" lab values in non-bleeding patients - this provides no benefit and increases risks 4
• Do not use antithrombin even if levels are low - robust evidence shows no benefit and increased bleeding 1, 4

Coagulation abnormalities typically resolve with successful treatment of the underlying sepsis, making source control and appropriate antimicrobial therapy the cornerstone of management. 4, 2