Use of Recombinant Activated Factor VII in Severe Post-Partum Haemorrhage: Data From the Italian Registry. A Multicentric Observational Retrospective Study.

Major Post-Partum Haemorrhage (PPH) is a life-threatening labour complication, which mainly occurs without warning, predictive signs or symptoms and often in absence of predisposing conditions. Severe PPH is defined by an estimated blood loss during the first 24 hours post-partum, of more than 500mL in case of natural delivery and of more than 1000mL in case of caesarean section. In developed countries PPH incidence is reported between 0.5% and 2%. In these countries it is the third cause of maternal mortality, after venous thromboembolism (VTE) and hypertension. In developing countries, major PPH is cause of 120-000-150.000 maternal deaths every year. Therapeutic strategies for severe PPH management are largely standardized. Recombinant activated factor VII (rFVIIa) is an activated factor VII form, produced from factor VII cDNA transfected into hamster kidneys. The first case of rFVIIa administration during perioperative bleeding has been reported in 1999, since this time rFVIIa has been used as adjunctive therapy in the management of patients with life-threatening and critical haemorrhages caused by trauma, abdominal or cardiac surgery or urological surgery, liver transplantation, post partum and any other bleeding condition leading to impairment of haemostasis

To report the Italian real experience in clinical practice, in order to provide wide and detailed clinical information about use of rFVIIa in the management of massive primary PPH in our country and in order to evaluate the role of haemostatic therapy in the management of this severe life- threatening obstetric complication, so contributing to treatment protocols development.

An Italian retrospective survey of severe primary PPH cases treated with rFVIIa was performed. Anamnestic, clinical and haemostatic data about fourty-three patients with PPH, from 2005 to 2007, were collected. Coagulative parameters and transfusion requirements before and after rFVIIa treatment were compared.

After rFVIIa administration INR was significantly decreased, while fibrinogen levels were markedly increased. Median of packed red blood cells units, platelets units, fresh frozen plasma, crystalloids and colloids needed, before and after rFVIIa administration, were significantly decreased (tab.1). Thirty-four of 43 patients needed surgical intervention before rFVIIa administration, 11/43 after treatment. Hysterectomies have been performed respectively in 12/43 cases before and in 7/43 cases after rFVIIa infusion. The response to rFVIIa is shown in table 2 No maternal deaths have been reported. No adverse events or thromboembolic complications were observed.

rFVIIa administration represents a safe haemostatic approach in the management of severe PPH cases, when other conventional medical, surgical and radiology interventional approaches have not been successful. Data from Italian Registry, as well as from other case series, demonstrate the rFVIIa efficacy to reduce or stop obstetric critical bleeding. The use of rFVIIa as lifesaving therapy in cases, in which medical and surgical standard approach have failed, should be always considered as life well as uterus lifesaving treatment.

Off Label Use: Safety and efficacy of rFVIIa in postpartum hemorrhage.