Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH.

Centre for Laboratory Medicine Haemostasis and Haemophilia Centre CH 9001 St Gallen Switzerland

Department of Anaesthesia Intensive Care Medicine Emergency Medicine and Pain Therapy Vivantes Klinikum in Friedrichshain DE 10249 Berlin Germany

Department of Haemostasis Disorders and Internal Medicine Laboratory of Haemostasis and Metabolic Diseases Institute of Haematology and Transfusion Medicine 02 776 Warsaw Poland

Department of Obstetrics and Gynaecology Semmelweis University H 1082 Budapest Hungary

Department of Paediatric Oncology University Hospital Brno and Masaryk University 613 00 Brno Czech Republic

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