Coagulation factor VIII plasma concentration

UF has also been used to concentrate antihemophilic coagulation factor VIII (AHF) with no measurable loss in activity it is particularly susceptible to thermal and shear denaturation. All of the other plasma proteins, including antithrombin III have been concentrated as well. 

A (congenital or acquired) and type 1 von Willebrand disease, in which the VWF protein structure is normal but the plasma concentration is reduced (1). By contrast with conventional coagulation factor concentrates, desmopressin is cheap and is free from the risk of transmission of viral infections, which have proved such a problem in the past. It is also very useful in the treatment of carriers of hemophilia A, many of whom have significant reductions in the baseline concentration of factor VIII. By contrast, desmopressin has no effect on the concentration of factor IX, and is thus of no value in hemophilia B (Christmas disease). It is also of little value in type 2 (abnormal VWF structure) von Willebrand s disease, which accounts for about 15-20% of all cases. The administration of desmopressin to patients with type 2B von Willebrand s disease can be hazardous, as it is likely to cause thrombocytopenia (2). The use of desmopressin in bleeding disorders has been reviewed (3). Tachyphylaxis develops if desmopressin is used for prolonged periods to control bleeding disorders, because desmopressin causes release of stored factor VIII and von Willebrand factor, after which it takes time for them to accumulate again. 

Plasma-derived factor VIII concentrates have been implicated in the transmission of the non-enveloped hepatitis A and parvovirus B19 (28). The virus-inactivating procedures now in use (chemical inactivation, wet-heat treatment, and nanofiltration) should provide coagulation factors without risk of transmitting HIV and with a very high safety for hepatitis virus. Nevertheless, recombinant factor VIII is considered a safer alternative. 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Ludlam CA. Viral safety of plasma-derived factor VIII and IX concentrates. Blood Coagul Fibrinolysis 1997 8(Suppl 1) S19-S23. 

Besides the production of polio and tetanus immunoglobulins, the fast growing company concentrated on the fractionation of human plasma on a larger scale. To this end, plasmapheresis was introduced as early as 1963 to increase the supply of human plasma. The application of Cohn s method of cold ethanol fractionation gradually enabled the production of a variety of common preparations, but also e.g. coagulation factor concentrates (factor VII, VIII and IX). Today the company processes about 10 % of the world supply of human plasma. 

Cryoprecipitate is a blood product that is manufactured from fresh frozen plasma. It contains a subset of coagulation factors fibrinogen (minimum of 150mg/unit), factor VIII (minimum 80IU/unit), von Willebrand factor (VWF) and factor XIII. With the production of recombinant and purified factor concentrates, the classical indications of haemophilia A and von Willebrand disease are no longer appropriate. Currently, cryoprecipitate is used to treat hypofibrinogemia. 

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