Viral inactivation vs biological activity.

The application of viral inactivation techniques to blood products, while preserving their biological functions, presents considerable problems, especially for coagulation factor concentrates, which are mostly impure preparations containing large quantities of plasma proteins and lipids. The three main methods which have been used are dry heat, solvent/detergent treatment and pasteurisation. Many factor VIII concentrates which have been produced using these methods display evidence of FVIII activation, with higher one-stage than two-stage potencies, more rapid FXa generation, and increased lower mol wt. polypeptides. Immunogenicity of FVIII is a particular concern, and recently a switch from dry heat to pasteurisation with one product was associated with an increased incidence of antibodies to FVIII in haemophilic recipients. Viral inactivation processes could also induce changes in non-FVIII components and these may be partly responsible for the immunosuppressive actions of some concentrates, observed both in vitro and in vivo. For factor IX concentrates thrombogenicity is a major potential hazard, and studies in the UK showed that the introduction of a viral inactivation step for one product increased its thrombotic potential, which had to be countered by addition of coagulation inhibitors. Coagulation inhibitor concentrates such as antithrombin III can be inactivated by pasteurisation, but this produces some heat denatured material which may be undesirable for the recipient.