title: Plasma derivatives: new products and new approaches.
abstract: The infusion of plasma-derived or recombinant factors to treat bleeding disorders such as hemophilia A and B is a success story in the management of a chronic disease. The effectiveness of this approach is however limited by challenges with adverse effects of treatment. The most notable of these are the development of inhibitory antibodies that target the protein therapeutic. The current standard of care for management of hemophiliacs is prophylactic treatment that includes frequent infusions of a Factor VIII product. Failure to comply with the prophylactic regimen is a major hurdle in the management of these patients. We discuss here more recent findings that argue for a pharmacogenetic approach to understanding (and eventually circumventing) immunogenicity. We also review strategies used to bioengineer coagulation factors to extend the half-lives of coagulation proteins. The rapid progress in the last few years to bioengineer coagulation factors in different ways to attain this goal is described. Finally, novel technologies and potential products are emerging that utilize synthetic molecules in lieu of replacement proteins obviating the limitations associated with replacement therapies.
authors.affiliation: Laboratory of Hemostasis, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Zuben E
authors.initials: ZE
authors.lastname: Sauna
authors.forename: Gouri Shankar
authors.initials: GS
authors.lastname: Pandey
authors.forename: Nisha
authors.initials: N
authors.lastname: Jain
authors.forename: Ifthekar
authors.initials: I
authors.lastname: Mahmood
authors.forename: Chava
authors.initials: C
authors.lastname: Kimchi-Sarfaty
authors.forename: Basil
authors.initials: B
authors.lastname: Golding
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D005164:Factor IX / Q000627:therapeutic use*; D005169:Factor VIII / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008074:Lipoproteins / Q000037:antagonists & inhibitors; D010949:Plasma / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D001779:Blood Coagulation Factors; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005169:Factor VIII; D005164:Factor IX