Semin Thromb Hemost 2013; 39(07): 752-766
DOI: 10.1055/s-0033-1356715
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systematic Review of the Role of FVIII Concentrates in Inhibitor Development in Previously Untreated Patients with Severe Hemophilia A: A 2013 Update

Massimo Franchini
1  Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantova, Italy
Antonio Coppola
2  Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy
Angiola Rocino
3  Hemophilia and Thrombosis Center, San Giovanni Bosco Hospital, Naples, Italy
Elena Santagostino
4  Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy
Annarita Tagliaferri
5  Regional Reference Centre for Inherited Bleeding Disorders, University Hospital, Parma, Italy
Ezio Zanon
6  Department of Cardiologic, Haemophilia Centre, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy
Massimo Morfini
7  Department of Emergency & Reception, Agency for Haemophilia, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
; Italian Association of Hemophilia Centers (AICE) Working Group› Author Affiliations
Further Information

Publication History

Publication Date:
10 September 2013 (online)


Nowadays, patients with hemophilia A receive a high standard of care; therefore, the most challenging complication of factor VIII (FVIII) replacement therapy has become the development of FVIII inhibitors, which render the concentrate infusion ineffective and expose patients to an increased risk of morbidity and mortality. Among environmental risk factors influencing inhibitor development, the type of FVIII products has always drawn the attention of investigators. Conflicting results are reported in the literature concerning rates of inhibitor development after either plasma-derived or recombinant FVIII concentrates. To help elucidate this controversial issue, we have performed a systematic review and meta-analysis of prospective studies evaluating the incidence of inhibitors in previously untreated patients with severe hemophilia A receiving plasma-derived or recombinant FVIII products. The quality of the studies was assessed using the Newcastle–Ottawa Scale (NOS), the STrenghtening the Reporting of OBservational studies in Epidemiology and an ad hoc quality score. Overall, 28 prospective studies, including 1,421 patients with hemophilia A, fulfilled our selection criteria and were included in the systematic review. No statistically significant differences were observed in the inhibitor incidence between plasma-derived and recombinant FVIII concentrates considering all (weighted means: 23%, 95% CI: 15–33% vs. 29%, 95% CI: 26–32%) and high titer (16%, 95% CI: 10–26% vs. 18%, 95% CI: 15–21%) inhibitors. Similarly, no significant differences were found in the inhibitor incidence among the different classes of recombinant products. In conclusion, the results of our meta-analysis show that the different types of FVIII products are not associated with different risks of inhibitor development.