Recombinant FVIIa (rFVIIa) was developed for treatment of haemophilia patients with
inhibitors against FVIII/FIX. The haemostatic efficacy rate of 80–90% including major
orthopaedic surgery (dosing of 90–120 µg/kg every other hour [h] for at least the
first 24 h) was achieved in these patients. In a home-treatment setting the efficacy
rate of haemostasis in mild-moderate bleedings was 92% (average number of 90 µg/kg
doses was 2.2). A wide individual variation regarding recovery of rFVIIa (46 ± 12%;
median 43%) as well as of clearance rate (36 ± 8 ml/kg/h; median 32 ml/kg/h in adults;children
2–3 times higher) has been observed. Thus children may require higher doses than adults.
Accordingly the use of a dose of 270 µg/kg in one single injection was approved in
the EU. Recent experience indicates that repeated doses of rFVIIa may decrease the
number of bleeds in “target joints”, and thus may be useful as prophylaxis in severe
hemophilia with inhibitors. Pharmacological concentrations of rFVIIa have been shown
to enhance the thrombin generation on thrombin activated platelets in a cell-based
model. By doing so a tight structured fibrin haemostatic plug resistant against premature
lysis is formed. rFVIIa has been shown to induce haemostasis not only in haemophilia
but also in other situations characterized by an impaired thrombin generation such
as platelet defects, dilution coagulopathy developed as a result of trauma and extensive
surgery. A special form of profuse bleeding, that may cause extensive problems is
postpartum haemorrhage.
Keywords
Factor VIIa - haemophilia therapy - haemostasis - haemophilia A / B - tissue factor
/ factor VII
