Role of recombinant factor VIIa in the clinical management of severe postpartum hemorrhage: consensus among European experts

Abstract

Objectives

There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a “last resort”, before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH.

Methods

The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data.

Results

The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation.

Conclusions

This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.

Keywords:

• Severe postpartum hemorrhage
• rFVIIa
• maternal mortality
• expert consensus
• guidelines
• hemostasis

Author contributions

D. Surbek, J. Blatný, M. Wielgos, N. Acs, H. Edwards, O. Erez, J. L. Bartha, H. Madar, and G. C. Di Renzo were involved in the face-to-face meeting and developed the initial consensus statements included in this study, coordinated by D. Surbek and G. C. Di Renzo. F. J. Mercier and D. Schlembach were included in the expert panel as external advisors to the consensus. All authors were involved in the refinement and finalization of the consensus statements included in this paper, and the consensus statements are based on clinical expertise, the current literature and the opinions of the experts. All authors were involved in writing this manuscript. All authors read and approved the final manuscript.

Disclosure statement

D. Surbek: advisory board and lecture honoraria from Novo Nordisk, CSL Behring, and Vifor (in part in favor of departmental research funding). J. Blatný: speaker and/or consultation fee from Novo Nordisk, Roche, Takeda, Octapharma, and Sobi. N. Acs: advisory board and lecture honoraria from Novo Nordisk. H. Edwards: advisory board for Novo Nordisk. F. J. Mercier: honoraria received by Novo Nordisk as speaker (symposium/webinar) and consultant. D. Schlembach: advisory board rFVIIa Novo Nordisk, Organon Advisory Board PPH, and CSL Behring – lecture fee (on PPH). M. Wielgos, O. Erez, J. L. Bartha, H. Madar, and G. C. Di Renzo have no conflicts of interest to declare.

Data availability statement

No new data were created or analyzed during this study. Data sharing is not applicable to this article.

Additional information

Funding

This process and open access to the publication were funded by Novo Nordisk A/S, Denmark. Medical writing support was provided by On Li Jasmine Lai, MSc and Tina Tremaine, PhD., of Bioscript Medical Communications, Macclesfield, UK and funded by Novo Nordisk.