FEIBA: Factor Eight Inhibitor Bypassing Activity
FEIBA is a first-line bypassing agent for treating acute bleeding episodes in hemophilia A or B patients with inhibitors, dosed at 50-100 units/kg every 8-12 hours (maximum 200 units/kg/day), with proven efficacy in controlling 88% of bleeding episodes and a critical role in prophylaxis where it reduces bleeding rates by 72.5% compared to on-demand treatment. 1, 2, 3
What FEIBA Is and How It Works
FEIBA is an activated prothrombin complex concentrate (aPCC) containing proenzymes of the prothrombin complex (prothrombin, Factor VII, Factor IX, Factor X) plus activated Factor VIIa, which bypasses the need for Factor VIII or IX by directly facilitating thrombin generation. 4
The mechanism centers on Factor Xa and prothrombin as key components, with the prothrombinase complex serving as the major target site for hemostatic activity. 4
FEIBA is plasma-derived and undergoes nanofiltration for viral safety, though it carries theoretical risks of infectious agents including viruses, vCJD, and CJD. 1
Clinical Indications
FEIBA is FDA-approved for three specific uses in hemophilia A or B patients with inhibitors: 1
- Control and prevention of acute bleeding episodes
- Perioperative management
- Routine prophylaxis to prevent or reduce bleeding frequency
FEIBA is NOT indicated for bleeding from coagulation factor deficiencies in the absence of inhibitors to Factor VIII or IX. 1
Dosing Protocols
For Acute Bleeding Episodes
Dose 50-100 units/kg every 8-12 hours, with frequency and duration determined by the type and severity of bleeding. 1
The mean initial dose in clinical practice is approximately 75 units/kg, most commonly administered twice daily. 2
Median treatment duration is 4 days for acute bleeding episodes (range 2-8 days). 2
Maximum daily dose must not exceed 200 units/kg per day to minimize thrombotic risk. 1
Maximum infusion rate must not exceed 10 units/kg/minute. 1
For Prophylaxis
Dose 85 units/kg every other day for routine prophylaxis. 1, 3
Prophylaxis reduces the annualized bleeding rate by 72.5% compared to on-demand treatment (median ABR 7.9 vs 28.7). 3
17.6% of patients on prophylaxis experienced zero bleeding episodes over one year. 3
Efficacy Data
FEIBA effectively manages 88% of bleeding episodes in acquired hemophilia A patients (95% CI: 75.8-94.5%). 2
In congenital hemophilia with inhibitors, prophylactic FEIBA significantly reduces all types of bleeding compared to on-demand treatment with comparable safety profiles. 3
Total FEIBA utilization for treating bleeding episodes is significantly lower during prophylaxis than on-demand therapy, making prophylaxis potentially more cost-effective. 3
Comparison with Recombinant Factor VIIa
Expert consensus indicates no clear superiority of FEIBA versus recombinant Factor VIIa (rFVIIa) for treating bleeding in inhibitor patients, as no head-to-head controlled trials have demonstrated one treatment as definitively more effective than the other. 5
Key Practical Differences:
FEIBA dosing mirrors Factor VIII/IX replacement (every 8-24 hours), while rFVIIa requires three initial doses at 2-3 hour intervals due to its 2-hour half-life. 5
Individual patients may respond better to one bypassing agent than the other, and responsiveness can change from one bleed to the next or even hour-to-hour during a single bleeding event. 6
Both bypassing products should be available, with early switching recommended if response to initial treatment is unsatisfactory. 6
For Surgical Procedures:
The 2024 ISTH guidelines suggest either rFVIIa or aPCC (including FEIBA) for invasive procedures in hemophilia A patients with inhibitors, with no evidence that one is superior to the other. 5
In patients receiving emicizumab prophylaxis, rFVIIa is preferred over FEIBA due to potential thrombotic complications when combining emicizumab with aPCCs. 5
Critical Safety Warnings
Thrombotic Risk (BLACK BOX WARNING):
Thromboembolic events have been reported particularly with doses above 200 units/kg/day and in patients with thrombotic risk factors. 1
Monitor all patients for signs and symptoms of thrombosis, stroke, pulmonary embolism, and deep vein thrombosis. 1
Absolute Contraindications:
- History of anaphylactic or severe hypersensitivity reactions to FEIBA or any components 1
- Disseminated intravascular coagulation (DIC) 1
- Acute thrombosis or embolism (including myocardial infarction) 1
Drug Interactions:
Do NOT use systemic antifibrinolytics (tranexamic acid, aminocaproic acid) within 6-12 hours of FEIBA administration due to increased thrombotic risk. 1
Combining FEIBA with rFVIIa creates marked synergistic effects on thrombin generation and should be reserved only for life- or limb-threatening bleeds refractory to single-agent therapy. 7, 8
Special Populations
Acquired Hemophilia A:
FEIBA is recommended as first-line therapy for severe bleeding in acquired hemophilia A patients, with dosing of 50-100 units/kg every 8-12 hours (maximum 200 units/kg/day). 5
In the prospective French FEIBHAC registry of elderly acquired hemophilia patients (mean age 81.8 years), FEIBA effectively managed 88% of bleeding episodes. 2
Hemophilia B with Inhibitors:
- FEIBA is safe and effective for hemophilia B patients with inhibitors, particularly those with allergic or anaphylactic reactions to Factor IX products where rFVIIa would otherwise be preferred. 5
Practical Clinical Pearls
Frequent evaluation of hemostatic efficacy during treatment is essential, as response can be unpredictable and may change hour-to-hour. 6
No baseline variables have been identified that reliably predict treatment response to FEIBA. 2
The most common adverse reactions (>5% of patients) are anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positivity, nausea, and vomiting. 1
FEIBA is available as lyophilized powder in single-dose vials containing 500,1000, or 2500 units per vial, for intravenous use after reconstitution only. 1