rhuFVIIa in Post-partum Hemorrhage
rhuFVIIa in Post-partum Hemorrhage
The aim of this clinical research project is to evaluate the use of the recombinant human
 activated factor VII (rhFVIIa), given as a salvage therapy, in women with a dramatic
 postpartum hemorrhage still ongoing after all the currently available medical and surgical
 treatments. We are going to compare its early use, before elective surgery or arterial
 embolization, to its late use, after embolization or surgery, before salvage hysterectomy.
Depending on the country and the publications, postpartum hemorrhage is either the first or
 the second cause of maternal death in the world, including developed countries. According to
 the WHO, it is responsible for twenty two percent of maternal deaths. In France, postpartum
 hemorrhage accounts for five percent of delivery complications. Three percent of them are
 severe, leading to uncontrolled bleeding which intensity is higher than 1000 ml of blood
 during the 24 hours following delivery. In France, they are involved in 20 new deaths per
 year; it is the first cause of maternal mortality. Indeed, it remains a significant source of
 morbidity: severe anaemia, blood transfusion, transfusion complications, acquired coagulation
 disorders and hemostatic hysterectomy.

 There are two different types of postpartum hemorrhage: early and late hemorrhages. Early
 hemorrhages are more common and occur in the first 24H after delivery. Uterine atony is the
 main cause of early hemorrhage. However, visual assessment underestimates the amount of blood
 loss in around forty five percent of cases. Emergency treatment is therefore sometimes
 undertaken with some delay, giving time for disseminated intravascular coagulation (DIC) to
 occur, which worsens the prognosis. They are usually treated by medical resuscitation, blood
 transfusion, selective arterial embolisation and finally hysterectomy in case of ongoing
 uncontrolled bleeding. Medical treatment and obstetric manoeuvres are usually effective.
 Artificial delivery of the placenta should be performed immediately if the placenta is
 incomplete. Afterwards, oxytocin and prostaglandin derivatives are given. At the same time,
 anemia and hemostatic abnormalities are treated by transfusion of fresh frozen plasma and
 packed cells. When the measures are insufficient, surgery is necessary. Bilateral ligation of
 hypogastric arteries or controlled embolisation is recommended. In the case of uncontrolled
 bleeding, hemostatic hysterectomy is performed as a salvage therapy. Also, the efficacy of
 ligation of the hypogastric arteries remains controversial. Therefore, the success rate of
 ligation of the hypogastric arteries is only forty two percent, so that in many cases
 hysterectomy is required, which induces a definitive sterility. The development of
 interventional radiology has offered a new approach for the management of postpartum
 hemorrhage. Many publications have showed the usefulness of the procedure, whose success rate
 is around ninety percent. However, a specific technical plateau is needed, which is far to be
 available at any place and at any moment. For patients delivering far away from these
 technical sites, limiting blood loss is crucial. Among the methods aiming at limiting
 obstetrical hemorrhage, special concern was given to recombinant activated factor VII, a drug
 used with good therapeutic results in symptomatic patients with hemophilia and inhibitors. It
 has already been applied in interventions situations.

 Taking into consideration the above described aspects, our goal is thus to evaluate the
 potential medical interest of giving rhFVIIa early in the course of hemorrhage, compared to
 giving it as a salvage therapy after arterial selective embolization or hysterectomy in
 patients still bleeding, in order to avoid hemostatic hysterectomy.

 In the literature, IV infusion of rFVIIa stopped ongoing diffuse hemorrhage, rapidly, and no
 further transfusion was required after rFVIIa injection. Then rFVIIa, might be a strong
 complementary agent in the management of major postpartum hemorrhage. Optimal dose, timing
 and safety characteristics of rFVIIa administration remain to be determined.

 Therefore, the main objectives of the study are:

 1. to evaluate the reduction of the absolute risk of arterial
 embolization/surgery/hysterectomy in patients receiving a unique early infusion of
 rhuFVIIa (60 µg/kg body weight);

 2. to evaluate the number of women necessary to treat to avoid one arterial
 embolization/surgery/hysterectomy.
Inclusion Criteria:

 -  Severe postpartum hemorrhage, i.e non responsive to sulprostone infusion

 Exclusion Criteria:

 -  < 18 years

 -  personal antecedent of arterial or venous thrombosis

 -  written informed consent not approved/signed by the patient or her husband