Annals of Hematology

, Volume 97, Issue 10, pp 1889–1901 | Cite as

Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia

  • Andreas Tiede
  • Andrew Worster
Original Article


To conduct a systematic review of the literature reporting efficacy and safety of recombinant factor VIIa (rFVIIa) for the treatment of bleeding in acquired haemophilia and, if data permitted, undertake a meta-analysis of the current evidence. MEDLINE®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for all studies on rFVIIa treatment in acquired haemophilia. Heterogeneity of included studies was measured using the inconsistency index (I2). Of the 2353 publications screened, 290 potentially relevant references were identified: 12 studies published in 32 publications met inclusion criteria. In total, 1244 patients and 1714 bleeds were included (671 patients received rFVIIa treatment for 1063 bleeds). In seven of 12 studies, the initial dose of Recombinant FVIIa was 90 ± 10 μg/kg. Recombinant FVIIa was used as first-line therapy in the majority of cases. Median number of doses administered ranged from 10 to 28. Between 68 and 74% of bleeds were spontaneous, whereas 4–50% were traumatic. Thirty-nine to 90% of bleeds were severe. Haemostatic effectiveness was > 90% in 5/6 studies for both patient and bleed level. Recombinant FVIIa had a favourable safety profile with low risk of general adverse events and thromboembolic-associated events. The heterogeneity of the studies and data precluded a meta-analysis. Recombinant FVIIa demonstrated effectiveness for the treatment of bleeds and had a good safety profile. It is apparent from these data that there is a need for more standardised measures of clinical effectiveness in acquired haemophilia to enable comparison and pooling of results in the future.


Acquired haemophilia Bleeding rFVIIa Systematic review Effectiveness Safety 



The authors would like to thank PAREXEL for performing the systematic review and tentative meta-analysis. Editorial and writing assistance was provided by Sharon Eastwood (DPhil) of Fishawack Communications Ltd and was financially supported by Novo Nordisk in compliance with international guidelines for good publication practice. The authors would also like to thank Soraya Benchikh el Fegoun of Novo Nordisk Health Care AG for her contributions to this project and comments during the development of the manuscript.

Author contribution

Both authors directed and critically evaluated the performance of the systematic review and tentative meta-analysis. Both authors also wrote and edited the manuscript and reviewed and approved the final submitted version.

Funding information

This study received financial support from Novo Nordisk.

Compliance with ethical standards

Conflict of interest

Andreas Tiede has received grants and personal fees for lectures and consultancy from Novo Nordisk. Andrew Worster has acted as a consultant for Novo Nordisk. The authors received an unrestricted grant from Novo Nordisk for editorial support during the development of the manuscript.

Ethical approval

For this type of study, ethical approval is not required.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

277_2018_3372_MOESM1_ESM.docx (67 kb)
ESM 1 (DOCX 67 kb)


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Copyright information

© The Author(s) 2018

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Hannover Medical School, Department of Haematology, Haemostasis, Oncology and Stem Cell TransplantationHannoverGermany
  2. 2.Division of Emergency MedicineMcMaster UniversityHamiltonCanada

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