The influence of pH on heat denaturation of anti-haemophilic cryoprecipitate.

The influence of pH on heat denaturation of anti-haemophilic cryoprecipitate (CP) was studied by using phosphate and citrate buffers at three different pH levels for processing lyophilized, heat treated CP. The solubility and the content of FVIII:C and fibrinogen were determined following heating at 68 degrees C for 24 hours and compared to "ordinary", non-heated CP. Both the solubility and the biological activity were best preserved in the most acidic samples (pH 5.7-6.7), these batches equalled non-heated CP. At higher pH, heat treatment resulted in reduced solubility and a more pronounced loss of FVIII:C and fibrinogen. Amino acids (Syntamin 17) have previously been shown to stabilize CP during heat treatment. Some of the stabilizing effect seems to be due to a large buffering capacity, maintaining a low pH during lyophilization and heating. Raising the pH level in Syntamin-CP from 6.6 to 7.8 resulted in decreased solubility and FVIII:C content. The quality of heat treated, acidic Syntamin-CP was comparable to that of heated, acidic phosphate- and citrate-CP. We conclude that buffers used for processing heat treated CP should be of low pH, and that acidic buffers may replace Syntamin without lowering the quality of the heated product.