How to assess the dose of Fibryga (fibrinogen) with ROTEM (Rotational Thromboelastometry)?

Assessing Fibryga Dosing with ROTEM

For optimal dosing of Fibryga (fibrinogen concentrate) using ROTEM, administer 3-4 g (or 50 mg/kg) when FIBTEM A10 is ≤10 mm or MCF is <7 mm, with each gram of fibrinogen expected to increase FIBTEM by approximately 2 mm.

Understanding ROTEM-Guided Fibrinogen Replacement

Baseline Assessment and Indications

• ROTEM provides real-time assessment of functional fibrinogen contribution to clot formation, making it preferable to laboratory fibrinogen measurement in bleeding patients 1
• Hypofibrinogenemia is the biomarker most predictive of severe postpartum hemorrhage and is often the first coagulation factor to critically decrease during massive blood loss 2, 1
• Fibrinogen supplementation is indicated when there are thromboelastometric signs of a functional fibrinogen deficit or plasma fibrinogen levels <1.5-2.0 g/L in the presence of significant bleeding 2, 3

ROTEM Parameters for Fibryga Dosing

• In trauma patients, a Maximum Clot Firmness (MCF) of 7 mm on ROTEM correlates with a fibrinogen level of approximately 2 g/L 2, 1
• FIBTEM A10 ≤10 mm is considered the threshold for fibrinogen replacement in bleeding patients 4
• For acquired fibrinogen deficiency, the FDA-approved dosing for Fibryga is:
  • Adults: 4 g
  • Adolescents ≥12 years: 50 mg/kg
  • Children <12 years: 70 mg/kg 4

Expected Response to Fibryga Administration

• For every gram of fibrinogen concentrate administered, expect approximately a 2-mm increase in the FIBTEM assay 1
• A single dose of Fibryga significantly increases MCF from baseline, with a mean change of 9.7 mm one hour post-infusion 4
• Fibryga contains a higher concentration of factor XIII (0.2 IU factor XIII per mg fibrinogen) compared to other fibrinogen concentrates, which may enhance clot firmness 1

Practical Algorithm for Fibryga Dosing with ROTEM

1. Initial Assessment:

   • Perform baseline ROTEM assessment focusing on FIBTEM A10 or MCF 2, 1
   • If possible, obtain plasma fibrinogen level simultaneously 3

2. Decision to Administer Fibryga:

   • Administer when FIBTEM A10 ≤10 mm or MCF <7 mm 4, 1
   • Alternatively, administer when plasma fibrinogen <1.5-2.0 g/L with significant bleeding 2, 3

3. Initial Dosing:

   • Adults: 4 g Fibryga 4
   • Adolescents ≥12 years: 50 mg/kg 4
   • Children <12 years: 70 mg/kg 4

4. Post-Administration Monitoring:

   • Repeat ROTEM assessment 1 hour after administration 4
   • Target FIBTEM A10 >10 mm or MCF >7 mm 1, 5
   • Target plasma fibrinogen level >200 mg/dL to limit massive transfusion requirements 5

5. Additional Dosing:

   • Administer additional doses if FIBTEM A10 remains ≤10 mm or plasma fibrinogen ≤200 mg/dL with continued bleeding 4, 5
   • For ongoing bleeding, maintain fibrinogen levels above 200 mg/dL 5

Clinical Considerations and Caveats

Efficacy Considerations

• A single dose of Fibryga is often sufficient to correct fibrinogen and FIBTEM A10 only when baseline fibrinogen is >100 mg/dL and FIBTEM A10 is >5 mm 5
• Patients with lower baseline values may require repeated dosing 5
• ROC curve analysis shows that post-treatment fibrinogen levels under 204.5 mg/dL predict the need for massive transfusion 5

Potential Pitfalls

• Laboratory methods to measure fibrinogen concentration may have methodological issues, particularly in the presence of artificial colloids like hydroxyethyl starch 1
• ROTEM provides more reliable assessment of functional fibrinogen in these situations 1
• While thrombotic risk is a theoretical concern with fibrinogen administration, studies have shown that intra-operative fibrinogen administration does not appear to increase thrombotic risk 1

Special Populations

• In pregnancy, fibrinogen levels <200 mg/dL are associated with severe postpartum hemorrhage, suggesting higher target levels may be needed in this population 2
• For women with congenital fibrinogen disorders during pregnancy, maintain fibrinogen levels ≥1 g/L throughout pregnancy and ≥1.5 g/L for labor and delivery 6