Contributions to the Optimization of Factor VIII Production: Cryoprecipitation and Controlled Pore Glass Adsorption

Abstract

The steadily increasing need for factor VIII complex to treat hemophilia A in an optimal way, nowadays causes a heavy demand for fresh-frozen plasma, from which this clotting factor is isolated. This is directly caused by the low recoveries of factor VIII coagulant activity (VIII:C) in most fractionation procedures, due to the lability of VIII:C as well as to the circumstance that also other plasma components are to be isolated from the plasma. Cryoprecipitation for instance usually yields recoveries of 300–500 units out of every 1000 that theoretically are present in 1 liter of starting plasma. Further purification to a high purity concentrate causes additional substantial loss. In routine practice therefore final recoveries of 100–200 IU/1 are normal which means that about 80% of the potential supply of VIII:C is spoilt. Yet, cryoprecipitation is still generally applied as the first step in factor VIII production, because of the purification obtained, the simplicity of the process and the fact that the other plasma proteins can still be isolated from the cryosupernatant. Although quite some literature has appeared in the past two decades dealing with the influence of several parameters on the recovery and purity of VIII:C in cryoprecipitate (e.g. 1,2), it is still not known by what mechanism the factor VIII complex is precipitating during freezing and thawing of plasma.