Managment of Deliveries in Carriers for Hemophila A and Low FVIII Levels with Recombinant FVIII Fc Fusion Protein

Introduction

It is well known that activitiy of coagulation factors rise significantly during pregnancy. Nevertheless some carriers for haemophilia A may have low factor levels and bleeding problems like male patients with mild hemophilia A. These female carriers may also face bleeding complications during delivery and after delivery. We report outcomes of deliveries in 3 carriers of haemophilia A who had previously experienced post partum haemorrhage. The women were treated with Efmoroctocog alfa two hours before delivery. We suspected that due to the fc fusion the factor VIII could cross the placenta into fetal blood, and reduce the risk of bleeding in the neoanate.

Samples and Methods

In three female patients we measured FVIII activity before pregnancy, in week 38 of gestation and 4 hours after delivery. 2 hours before delivery 2000 IU Efmoroctocog alfa were given. The cord blood of the neonates (one with severe hemophilia A, one wildtype and two fraternal twins with mild hemophilia) was taken after birth and a venous blood sample was drawn 1 day after birth to measure FVIII activity. The FVIII activity was analyzed with a chromogenic assay (FVIII chromogenic assay, on the Behring Coagulation System BCS, Siemens healthcare GmbH, Germany)

Results

In two women FVIII decreased during pregnancy by 20% and 28%, respectively. In the other woman we saw an increase of 28%. In the carrier of the severe hemophilia we observed only an increase of 2% after the administration of 2000 IU of FVIII, while in the other two with decreased FVIII an increase of 89% and 90% was noted. This was much more effective.

In the new born with a mutation for a severe hemophilia A we could not see any effect of the donation of Efmoroctocog alfa. The activity of FVIII was below 1% in the cord blood and the venous blood sample.

We observed no thrombotic complications after the use of Efmoroctocog alfa. The woman delivering the twins by ceasarian section experienced a strong post partum bleeding and was successfully treated with tranexamic acid.

Discussion/Conclusion

In healthy patients we see benefit in increasing FVIII levels during pregnancy, in carriers of hemophilia A it could be the opposite. Therefore they should be monitored particularly before and after delivery. We have no signs due to this limited data, that the use of an factor VIII concentrate with a prolonged half-life could be an advantage against the use of a common concentrate.

We hypothesized that due to the fusion of a recombinant FVIII to an Fc-part of an immun globuline this molecule is able to cross the placenta into the fetal blood. The case of the boy with the severe hemophilia A refutes this, because we were not able to measure any FVIII activity in his blood. So the use of Efmoroctocog alfa seems to have no sufficient effect on the fetal blood.