Systematic review of the role of FVIII concentrates in inhibitor development in previously untreated patients with severe hemophilia A: A 2013 update

Massimo Franchini, Antonio Coppola, Angiola Rocino, Elena Santagostino, Annarita Tagliaferri, Ezio Zanon, Massimo Morfini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)752-766
Number of pages15
JournalSeminars in Thrombosis and Hemostasis
Issue number7
Publication statusPublished - 2013


  • bleeding
  • FVIII concentrates
  • inhibitors
  • plasma derived
  • recombinant
  • systematic review
  • therapy

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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