Measurement of Activated Factor VII Using Soluble Mutant Tissue Factor -Proposal for Standardization

Currently marketed plasma-derived FVIII and FIX concentrates are prepared from donor screened (HIV, HCV, HBsAg, etc) recovered or source plasmas and subjected to a variety of purification and viral inactivation procedures (I). Published data confirming the viral safety of currently available plasma-derived clotting factor concentrates to prevent transmission of human pathogenic viruses are scanty or nonexistent for many products (2). For example: 1for several products (Bebulin®, Monoclate P®, Mononine®, Alphanine-SD®, eg), there have been only a few (<20) prospectively and longitudinally evaluable patients to document HCV safety; 2there have been no data published concerning long-term transmission/safety for human parvovirus with any product; 3there have been no studies for HCV transmission with Autoplex® and Feiba®. There is a great need to have such information for each replacement product, in order to make therapeutic decisions affecting patients' lives. Currently, the laboratory tools are available and adequately sensitive to detect the viral exposure of hemophiliacs using these products to render these clinical studies feasible and relevant: 1for the last 6 years, HCV transmission by FVIII concentrates has been unusual, making possible HCV transmission/safety studies for Autoplex® or Feiba®; 2reliable tests for human parvovirus IgM and IgG also are now available, allowing prevalence studies to compare hemophiliacs treated since birth with only one brand of product to control groups of children matched for age and country. Although anecdotal reports from the manufacturers allege that no transmission of various viruses by their products has been reported, this does not provide a definitive proof of the ultimate viral safety of those products. Similarly the results of viral loading studies do not provide a definitive answer as they are mostly performed using model viruses. Moreover, although we assume that the approval by the regulatory agencies required viral loading studies for all replacement therapy con-