Table 1.

Characteristics and licensed regimens of bypassing agents for the treatment of patients with HR inhibitors.

Bypassing Agent	Activated Prothrombin Complex Concentrate (aPCC)	Recombinant Activated Factor VII (rFVIIa)
Source	Pooled human plasma	Recombinant coagulation FVIIa produced in baby hamster kidney (BHK) cells by recombinant DNA technology (Eptacog alfa)
Therapeutic indications	Treatment of spontaneous bleeding and cover of surgical interventions in: haemophilia A patients with inhibitors to FVIII patients with acquired inhibitors to FVIII prophylaxis in haemophilia A patients with HR inhibitors and frequent joint bleeding.	Treatment of bleeding episodes and cover of surgical interventions in: -patients with congenital haemophilia with inhibitors to FVIII or FIX >5 BU -patients with congenital haemophilia who are expected to have a high anamnestic response to FVIII or FIX administration -patients with acquired haemophilia.
Recommended regimen(s)	50 to 100 U*/kg Dose interval: 6–12 h. A single dose of 100 U/kg and a daily dose of 200 U/kg should not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses. For prevention of bleeding episodes during prophylaxis, 70 to 100 U/kg every other day with dose adjusted based on the patient’s clinical response.	Initial dose: 90 μg/kg Dose interval: 2–3 h until haemostasis is achieved. If continued therapy is needed, the dose interval can be increased successively to every 4, 6, 8 or 12 h for as long as treatment is judged as being indicated. For mild to moderate bleeding episodes (including home therapy) two dosing regimens can be recommended: (1)Two to three injections of 90 μg/kg at 3-h intervals. If further treatment is required, one additional dose of 90 μg/kg (2)One single injection of 270 μg/kg. The duration of home therapy should not exceed 24 h.
Storage requirements	Room temperature (up to 25 °C) for up to 2 years.	Room temperature (up to 25 °C) for up to 2 years.
Volume	Diluent volume: 20 mL.	Diluent volume: 1.1 mL (1 mg); 2.1 mL (2 mg); 5.2 mL (5 mg).
Time of administration	The rate of intravenous administration should ensure the comfort of the patient and should not exceed a maximum of 2 U/kg per minute.	Intravenous bolus injection over 2–5 min
Half-life in plasma	Varying half-lives for the single components (FII, FIX, FX, FVIIa)	2.3 h (range 1.7–2.7)
Inhibitor anamnesis	Possible in about 20%–30% of patients, since FVIII coagulant antigen (FVIII C:Ag) is present in a concentration of up to 0.1 U/1 U of aPCC. Upon continued administration, inhibitors may decrease over time.	No
Association with antifibrinolytic agents	Systemic antifibrinolytics should be administered at least 6 h apart.	Commonly used.
Laboratory monitoring	Not standardised	Not standardised
Thrombotic risk	Yes	Yes

* One unit is defined as that amount of the product that shortens the activated partial thromboplastin time of a high titre FVIII inhibitor reference plasma to 50% of the blank value.