Lipolytic versus proteolytic degradation of human factor VIII

Variable Degradation of Factor VIII-Related Protein in Lyophilised Concentrates of Antihaemophilic Factor (AHF)

“…This ratio remained stable upon storage for several weeks at 4 °C of highly purified material, in contrast to VIII:C which disappeared gradually. In some of our factor VIII preparations, as well as in com mercial factor VIII concentrates, the VIII R:AG/VIII R:WF ratio was greater than 2.0 and increased upon prolonged storage, dialysis at room temperature [3] or follow ing deliberate enzymatic degradation [5],…”

“…Irreversible deg radation, e.g. by plasmin, is accompanied by a rapid loss of VIII:C, a slower inactiva tion of VIII R:WF and an apparent increase of VIII R:AG measured by crossed immunoelectrophoresis [5], Analysis of reduced factor VIII indicated a reduction of the mo lecular size of the typical subunit chain fol lowing proteolytic degradation [5,12].…”

“…By convention, haemophiliacs have been treated with a biological entity lacking in their plasma and bearing the neutral desig nations antihaemophilic factor, factor VIII or VIII:C. Since we now know that VIII:C is associated with other related subunits (or activities) in a macromolecular complex, one should not overlook the fate of this complex during plasma fractionation. Our approach to quality assessment of factor VIII concentrates was deduced from experi ments indicating that factor VIII complex may be reversibly or irreversibly degraded by several enzymes [5,8]. Irreversible deg radation, e.g.…”

Variable Degradation of Factor VIII‐Related Protein in Lyophilised Concentrates of Antihaemophilic Factor (AHF)1

“…This ratio remained stable upon storage for several weeks at 4 ^C of highly purified material, in contrast to VII1:C which disappeared gradually. In some of our factor VIII preparations, as well as in commercial factor VIII concentrates, the VIII R:AG/VIII R:WF ratio was greater than 2.0 and increased upon prolonged storage, dialysis at room temperature [3] or following deliberate enzymatic degradation [5].…”

“…By convention, haemophiliacs have been treated with a biological entity lacking in their plasma and bearing the neutral designations antihaemophilic factor, factor VIIl or V1II:C. Since we now know that V1II:C is associated with other related subunits (or activities) in a macromolecular complex, one should not overlook the fate of this complex during plasma fractionation. Our approach to quality assessment of factor VIII concentrates was deduced from experiments indicating that factor VIII complex may be reversibly or irreversibly degraded by several enzymes [5,81. Irreversible degradation, e.g.…”