Table IV.

Advantages and limitations of the different approaches available for treatment of bleeding in patients with acquired haemophilia A^§

Therapeutic approach	Recommended dose	Advantages	Limitations
Bypassing agents
aPCC	50–100 U/kg every 8–12 h, until achievement of haemostasis, then at longer intervals as required Maximum 200 U/kg daily	Efficacy demonstrated in various studies and registries Often available even in non-specialised centres	No validated laboratory monitoring assay Potential risk of arterial or venous thromboses Large infusion volumes Possible anamnestic response#
rFVIIa	90–120 μg/kg every 2–3 h until achievement of haemostasis, then at longer intervals as required	Efficacy demonstrated in various studies and registries Generally available even in non-specialised centres Flexibility of dose regimens	No validated laboratory monitoring method Potential risk of arterial or venous thromboses Short half-life (2–3 h)^
Replacement therapy ∘
Human FVIII (plasma-derived or recombinant)	Variable depending on severity of bleeding, inhibitor titre, infusion modality (boluses or continuous infusion)	Efficacy demonstrated in some studies, in the case of low-titre inhibitors (<5 BU) Laboratory monitoring (FVIII activity) Readily available also in non-specialised centres	Possible anamnestic response High doses of concentrate required Laboratory assays must be performed at least daily
rpFVIII	Starting dose 200 IU/Kg, subsequent maintenance doses in relation to the clinical response, FVIII levels (measured 30 min and 3 h after infusion) and the type/severity of bleeding; generally, infusions every 4–12 h*	Efficacy demonstrated (but studies still limited) Laboratory monitoring (one-stage FVIII activity)	Possible development of anti-rpFVIII antibodies, with consequent reduced efficacy Not always readily available Need for round-the-clock laboratory services

aPCC: activated prothrombin complex concentrate; rFVIIa: activated recombinant factor VII concentrate; rpFVIII: recombinant porcine factor VIII concentrate.

^§Specific approvals and indications in acquired haemophilia A (AHA) can be different across countries. The European Medicine Agency (EMA) licensed aPCC, rFVIIa and rpFVIII for treatment of bleeding in AHA patients, while aPCC is not specifically approved for this indication by the Food and Drug Administration (FDA). The use for prevention of bleeding in the case of surgery or invasive procedures is approved for rFVIIa by EMA and FDA.

^#Increase of inhibitor titre, due to the presence of small amounts of FVIII.

^{^}Limitation overcome by the possible administration in a syringe pump (polypropylene 50 mL) at timed intervals, since the drug is stable after reconstitution for 24 h at 25°C, under close clinical monitoring.

^∘This approach also includes the administration of desmopressin (DDAVP), reported in patients with low inhibitor titres, but difficult in clinical practice because of the poor predictability of response, the possible tachyphylaxis and the risk of adverse events in the elderly and patients with comorbidities.

^*Dose regimen and monitoring indications from the product information leaflet, taken from the registration study, in which patients with anti-rpFVIII cross-reactivity <20 BU/mL were enrolled. Data are available from case series in which lower doses (50–120 IU/kg) were used for initial treatment, while subsequent doses were defined by monitoring clinical response and FVIII levels.