Thiol Groups in the Blood Clotting Action of Factor VIII

S ummary . Investigations have been carried out on the chemical groupings in factor VIII with a view to discovering the biochemical mechanisms involved, and the chemical groups responsible, for its particular blood clotting properties. Bovine factor VIII has been treated with iodine, hydrogen peroxide, iodoacetamide and the sodium salt of p‐Chloromercuribenzoic acid. Each of these reagents is known to react with thiol groups. Each inactivates factor VIII and, in the case of the mer‐ cury compound, factor‐VIII activity can be regenerated using cysteine. Preliminary results indicate that similar effects are obtained using human factor VIII. It is concluded that factor VIII contains thiol groups situated at or near to the active sites of clotting. Possible applications of these new findings are also discussed. In particular, it may provide more insight into the storage stability of factor‐VIII concentrates.