title: Von Willebrand factor-containing factor VIII concentrates and inhibitors in haemophilia A. A critical literature review.
abstract: The development of inhibitors that neutralise the function of factor VIII (FVIII) is currently not only the most challenging complication associated with the treatment of haemophilia A but it also increases the disease-related morbidity as bleeding episodes do not respond to standard therapy. The main short-term goal of the treatment of inhibitor patients is to control bleeding episodes while the long-term one is to permanently eradicate the inhibitor by immune tolerance induction, particularly in the case of high-titer antibodies. Due to some in vitro studies and clinical observations, some investigators have suggested that FVIII concentrates containing von Willebrand factor (VWF) may be less immunogenic than high-purity or recombinant FVIII products. It has also been suggested that success rates for immune tolerance induction are higher when plasma-derived FVIII products are used. The currently available data from laboratory and clinical studies on the role of VWF in inhibitor development and eradication in haemophilia A is critically analysed in this review. As a result, we have not found definitive evidence supporting a role for product type on inhibitor incidence and inhibitor eradication in haemophilia A patients.
authors.affiliation: Servizio di Immunoematologia e Trasfusione, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. mfranchini@ao.pr.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lippi
mesh_terms: D000906:Antibodies / Q000097:blood*; D003029:Coagulants / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004338:Drug Combinations; D000939:Epitopes; D019317:Evidence-Based Medicine; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D017410:Practice Guidelines as Topic; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D017211:Treatment Failure; D014841:von Willebrand Factor / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D003029:Coagulants; D004338:Drug Combinations; D000939:Epitopes; D011994:Recombinant Proteins; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII