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. 2018 Oct;97(10):1889-1901.
doi: 10.1007/s00277-018-3372-z. Epub 2018 May 26.

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

Andreas Tiede  1 , Andrew Worster  2
Affiliations

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

Andreas Tiede et al. Ann Hematol. 2018 Oct.

Erratum in

Abstract

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.

Keywords: Acquired haemophilia; Bleeding; Effectiveness; Safety; Systematic review; rFVIIa.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Flow of studies through the systematic review process. AH, acquired haemophilia; CA, conference abstract; CSR, clinical study report; Embase, Excerpta Medica Database; MEDLINE, Medical Literature Analysis and Retrieval System Online; N, number of studies; n, number of publications; SGA, sub-group analysis
Fig. 2
Fig. 2
Forest plot for the haemostatic effectiveness using data extracted from the individual studies at a patient level (fixed-effect model) and b bleed level (random-effects model). CI, confidence interval
See this image and copyright information in PMC

References

    1. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR, Organisation UKHCD Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood. 2007;109(5):1870–1877. doi: 10.1182/blood-2006-06-029850. - DOI - PubMed
    1. Borg JY, Guillet B, Le Cam-Duchez V, Goudemand J, Levesque H, Group SS Outcome of acquired haemophilia in France: the prospective SACHA (Surveillance des Auto antiCorps au cours de l'Hemophilie Acquise) registry. Haemophilia. 2013;19(4):564–570. doi: 10.1111/hae.12138. - DOI - PubMed
    1. Knoebl P, Marco P, Baudo F, Collins P, Huth-Kuhne A, Nemes L, Pellegrini F, Tengborn L, Levesque H, Contributors ER. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2) J Thromb Haemost. 2012;10(4):622–631. doi: 10.1111/j.1538-7836.2012.04654.x. - DOI - PubMed
    1. Tiede A, Klamroth R, Scharf RE, Trappe RU, Holstein K, Huth-Kuhne A, Gottstein S, Geisen U, Schenk J, Scholz U, Schilling K, Neumeister P, Miesbach W, Manner D, Greil R, von Auer C, Krause M, Leimkuhler K, Kalus U, Blumtritt JM, Werwitzke S, Budde E, Koch A, Knobl P. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood. 2015;125(7):1091–1097. doi: 10.1182/blood-2014-07-587089. - DOI - PMC - PubMed
    1. Franchini M, Mannucci PM. Acquired haemophilia A: a 2013 update. Thromb Haemost. 2013;110(6):1114–1120. doi: 10.1160/TH13-05-0363. - DOI - PubMed

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