title: How we choose factor VIII to treat hemophilia.
abstract: In high-income countries, the large availability of coagulation factors for replacement therapy of patients with hemophilia A has raised the life expectancy of these lifelong bleeders to that of males from the general population. The practicing clinician is offered a multitude of choices among several commercial brands of factor VIII extracted from human plasma or engineered from mammalian cell cultures by means of recombinant DNA technology. This article has the goal to offer our opinions on how to choose among the different products, that we consider interchangeable relevant to their clinical efficacy in the control of bleeding and safety from pathogen transmission. Hence, the main determinants of our choices are price and the risk of occurrence of factor VIII inhibitory alloantibodies. With this as background, we present the rationale underlying the choices for different categories of patients with severe hemophilia A: previously untreated patients, multiply treated patients, and patients undergoing immune tolerance induction with large doses of factor VIII to eradicate inhibitors. Mention is also made to the possible strategies that should be implemented to make available coagulation factors for replacement therapy in developing countries.
authors.affiliation: Scientific Direction, Department of Medicine and Medical Specialties, Istituto di Ricovero eCura a Carattere Scientifico Cá Granda Maggiore Policlinico Hospital Foundation, Milan, Italy. pmmannucci@libero.it
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Mancuso
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000818:Animals; D017848:Blood-Borne Pathogens; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D019049:Developed Countries; D003906:Developing Countries; D004340:Drug Contamination; D016527:Drug Costs; D005169:Factor VIII / Q000009:adverse effects / Q000191:economics / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000191:economics; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007349:Insurance, Health, Reimbursement; D007518:Isoantibodies / Q000096:biosynthesis; D007558:Italy; D008297:Male; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000191:economics / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D013045:Species Specificity
chemical_list: D007518:Isoantibodies; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII