A LOW pH PREVENTS DENATURATION OF HEAT TREATED ANT I -HAEMOPHILIC CRYOPRECIPITATE

O Skjonsberg, K Gravem, P Kierulf, H Godal
1987 PLATELET GYCOPROTEINS IIb-IIIa   unpublished
The AIDS epidemic has necessitated heat treatment of FVIII:C products in order to inactivate HIV-virus. When antihaemophilic cryoprecipitate (CP) is heated (68°C, 24 hours), the solubility and the concentration of FVIIIrC, von Willebrand factor and fibrinogen are substantially reduced. Such heat denaturation is prevented by addition of synthetic amino acids (SyntaminR 17) prior to lyophilization and heat treatment (Ref.rMargolis and Eisen, Skjønsberg et al.). The exact mechanism of this
more » ... ve effect is not known, but in our opinion, the large buffering capacity of Syntamin is of major importance. Thus, in the presence of Syntamin (4 mg/unit FVIIIrC), a pH of 7.4 was maintained during lyophilization and heat treatment, while in ordinary CP, pH rose from 7.8 to 8.6 during the same procedure. Moreover, heat denaturation of CP was prevented by replacing Syntamin with a phosphate buffer, keeping a stable pH below 7.4. It is of interest to notice that apart from the effect on pH, we were unable to observe any influence of Syntamin on heat denaturation of plasma proteins in solution, on degradation of FVIII:C and fibrinogen by thrombin or plssmin or on the solubility of fibrin in plasma and CP.Heat treatment of CP at various pHs indicated that the :est product was obtained when pH .was kept between 6.5 and 6.3. By using an acidic buffer instead of Syntamin, the disadvantages of the latter, such as increased residual moisture leading tc discolouration, a probable stabilizing effect on virus and increased costs, may be avoided.
doi:10.1055/s-0038-1643968 fatcat:akvk27kn4bdvfeqfnomt7adez4