What is the role of Fibryga (Fibrinogen) and Rotem (Rotational Thromboelastometry) in managing acute bleeding episodes?

Fibryga and ROTEM in Managing Acute Bleeding Episodes

Fibryga (fibrinogen concentrate) is indicated for fibrinogen supplementation in bleeding patients with acquired fibrinogen deficiency, while ROTEM (Rotational Thromboelastometry) provides crucial real-time assessment of clot formation to guide targeted fibrinogen replacement therapy. 1, 2

Fibryga: Clinical Applications and Dosing

• Fibryga is a human fibrinogen concentrate indicated for fibrinogen supplementation in bleeding patients with acquired fibrinogen deficiency and for treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency 1

• Fibryga contains a higher concentration of factor XIII (0.2 IU factor XIII per mg fibrinogen) compared to other fibrinogen concentrates, which may explain the increased maximum clot firmness observed with thromboelastometry 3

• For acquired fibrinogen deficiency in adults, the recommended dose is 4g, with additional doses administered when plasma fibrinogen level is ≤200 mg/dL or ROTEM FIBTEM A10 is ≤10 mm 1

• For congenital fibrinogen deficiency, the target plasma fibrinogen level is 100 mg/dL for minor bleeding and 150 mg/dL for major bleeding 1, 4

• Fibryga has demonstrated efficacy in treating bleeding episodes with a 96.6-98.9% treatment success rate according to investigator and independent committee evaluations 5

ROTEM in Fibrinogen Management

• ROTEM provides real-time assessment of clot formation, strength, and stability, allowing for targeted fibrinogen replacement therapy in bleeding patients 2

• The FIBTEM assay specifically evaluates the fibrinogen contribution to clot strength by using cytochalasin D to inhibit platelet function 2, 6

• In trauma patients, a Maximum Clot Firmness (MCF) of 7 mm on ROTEM is associated with a fibrinogen level of approximately 2 g/L 3

• ROTEM FIBTEM shows better association with the Clauss fibrinogen assay (correlation ranging from 0.27 to 0.94) compared to TEG functional fibrinogen assay (correlation ranging from 0 to 0.9) 2

• For every gram of fibrinogen concentrate administered, there is an expected 2-mm increase in the fibrin-based thromboelastometry assay (FIBTEM) 3

Algorithm for Managing Acute Bleeding with Fibryga and ROTEM

1. Initial Assessment:

   • Perform ROTEM analysis to evaluate clot formation and identify fibrinogen deficiency 3, 2
   • Focus on FIBTEM MCF/A10 parameters to specifically assess fibrinogen contribution to clot strength 2, 6

2. Decision to Administer Fibryga:

   • Administer Fibryga when significant bleeding is accompanied by thromboelastometric signs of functional fibrinogen deficit or plasma fibrinogen level <1.5-2.0 g/L 3
   • FIBTEM A10 ≤10 mm indicates need for fibrinogen replacement 1, 2

3. Initial Dosing:

   • Adults: 4g of Fibryga 1
   • Adolescents (≥12 years): 50 mg/kg body weight 1
   • Children (<12 years): 70 mg/kg body weight 1

4. Monitoring and Subsequent Dosing:

   • Reassess with ROTEM after initial dose 3, 2
   • Administer additional doses if FIBTEM A10 remains ≤10 mm or plasma fibrinogen level is ≤200 mg/dL 1
   • For every gram of fibrinogen concentrate administered, expect a 0.2-0.3 g/L increase in Clauss fibrinogen level and 2-mm increase in FIBTEM 3

Clinical Efficacy and Considerations

• Fibrinogen is the first coagulation factor to critically decrease during massive blood loss, making early assessment and replacement crucial 3

• Administration of fibrinogen concentrate has been associated with reduction in blood transfusion requirements in bleeding patients 3

• ROTEM-guided fibrinogen administration may be preferable to laboratory fibrinogen measurement, as it provides real-time assessment of functional fibrinogen contribution to clot formation 3

• The higher factor XIII content in Fibryga may provide additional benefit in improving clot firmness compared to other fibrinogen concentrates 3

Pitfalls and Caveats

• Laboratory methods to measure fibrinogen concentration may have methodological issues, particularly in the presence of artificial colloids like hydroxyethyl starch, which can cause the Clauss method to overestimate fibrinogen concentration 3

• While fibrinogen replacement is crucial for hemostasis, there is limited high-quality evidence from prospective clinical trials demonstrating risk-benefit analysis in trauma patients 3

• ROTEM and TEG functional fibrinogen assays are correlated but not interchangeable; results from one system should not be used to guide therapy based on thresholds established for the other system 2

• Although thrombotic risk is a theoretical concern with fibrinogen administration, studies have shown that fibrinogen levels naturally rise to approximately 7 g/L after major surgery and trauma, and intra-operative fibrinogen administration does not appear to increase thrombotic risk 3