PROTEIN AGGREGATES IN HEATED BLOOD PRODUCTS
XIth International Congress on Thrombosis and Haemostasis
Heating of blood products to reduce viral infectivity is now a standard practice. Such treatment may also modify the constituent proteins, reducing their activity or altering their structure with potentially harmful consequences for the recipient. Partially denatured proteins frequently form aggregates, which are often immunogenic and could precipitate immune complex formation, allergic reactions and kidney damage. In addition they may contribute to the development of AIDS after HIV infection
... ter HIV infection by inducing a persistent state of T-cell activation.Protein aggregate formation in factor VIII and factor IX (II + X) concentrates has been investigated by fast protein liquid chromatography (FPLC), which proved to be a rapid, convenient method for this purpose. Freeze-drying alone resulted in aggregate formation in intermediate purity FVIII concentrates, but not in FIX concentrates. However, aggregates were detected after heating the FIX concentrate at 80°C for 72h in the dry state. Dry heating of intermediate purity FVIII concentrates to 68°C for 24h also increased the content of protein aggregates, which contained fibrinogen and fibronectin but little IgG. In this product, the aggregate content after heating correlated with total protein concentration. A higher purity FVIII concentrate selectively depleted in fibrinogen and fibronectin also contained protein aggregates after freeze-drying, but heating this product at 80°C for 72h resulted in a relatively small increase in aggregate content. Haemophiliacs receiving regular injections of heated concentrates are constantly exposed to protein aggregates. They should be monitored for any harmful effects, and manufacturers should aim to reduce the aggregate content of their products.