The safety of pharmacologic options for the treatment of persons with hemophilia

ABSTRACT

Introduction: The mainstay of treatment of hemophilia A and B is the replacement of the congenitally deficient coagulation factor through the intravenous infusion of specific concentrates (factor VIII, FVIII, in hemophilia A; factor IX, FIX, in hemophilia B). Several commercial brands of FVIII or FIX products extracted from human plasma or engineered using recombinant DNA technology are available.

Areas covered: We analyze the safety aspects of plasma-derived and recombinant FVIII and FIX products licensed in Europe, focusing on their pathogen safety and inhibitor and thrombosis risks. The safety aspects of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII) used for treatment of bleeding episodes in inhibitor patients will be also briefly discussed.

Expert opinion: The analysis of the published literature documents the high degree of safety from pathogen risk for both plasma-derived and recombinant products available for hemophilia treatment. The main threat to factor concentrate safety is represented by the development of neutralizing alloantibodies against the infused coagulation factor, which in hemophilia A seem to occur more frequently following the administration of recombinant than plasma-derived FVIII products. Great expectations are placed on newer products, particularly on those based upon mechanisms of action other than FVIII replacement.

KEYWORDS:

• Hemophilia
• safety
• pathogens
• inhibitors
• thrombosis

Article highlights

• Replacement therapy with FVIII or FIX concentrate is the mainstay of treatment of hemophilia A or B

• The availability of high-quality plasma derived and recombinant factor concentrates has greatly contributed to the improved quality of life and reduced morbidity in the hemophilia community.

• Thanks to the modern techniques of fractionation and viral inactivation, both plasma derived and recombinant products have nowadays a high degree of safety against the risk of pathogen transmission.

• Thrombotic adverse events associated with the use of the currently available FVIII and FIX concentrates occur rarely.

• The main unresolved complication of replacement therapy for hemophilia is the development of inhibitory alloantibodies.

This box summarizes key points contained in the article.

Declaration of interest

PM Mannuci declares to have received honoraria for lectures as speaker or chair symposia organized by Bayer, Grifols, Kedrion, LFB, Novo Nordisk and Pfizer. He also acted a scientific consultant for Bayer, Baxalta and Kedrion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

There was no funding for this paper.