Recombinant blood products and therapeutic enzymes - Pharmaceutical Biotechnology: Concepts and Aapplications - page 338

Liver cell Endothelial cell

Liver cell Endothelial cell Liver cell Endothelial cell

vWF

Plasma

Factor VIII C

Factor VIII C

vWF

Rapid degradation
of VIII C

Factor VIII
complex
(VIII C: vWF)
(a) (b) (c)

Figure 12.6 (a) Synthesis of factor VIII complex as occurs in healthy individuals. (b) In the case of persons
suf fer ing from haemophilia A, synthesis of factor VIII:C is blocked, thus preventing constitution of an active factor
VIII complex in plasma. (c) Persons suffering from von Willebrand's disease fail to synthesize vWF. Although they
can synthesize VIII:C, this is rapidly degraded upon entering the blood due to lack of its vWF stabilizing factor

Persons suffering from (the rarer) von Willebrand's disease lack both components of mature fac-
tor VIII complex (Figure 12.6). The severity of the resultant disease is somewhat dependent upon
the level of intact factor VIII complex produced. Persons completely devoid of it (or expressing
levels below 1 per cent of normal values) will experience frequent, severe and often spontaneous
bouts of bleeding.
Persons expressing 5 per cent or above of the normal complex levels experience less severe
clinical symptoms. Treatment normally entails administration of factor VIII complex purifi ed
from donated blood. More recently, recombinant forms of the product have also become available.
Therapeutic regimens can require product administration on a weekly basis, for life. About 1 in
10 000 males are born with a defect in the factor VIII complex and there are approximately 25 000
haemophiliacs currently resident in the USA.

12.2.5 Production of factor VIII

Native factor VIII is traditionally purifi ed from blood donations fi rst screened for evidence of the
presence of viruses such as hepatitis B and HIV. A variety of fractionation procedures (initially
mainly precipitation procedures) have been used to produce a factor VIII product. The fi nal prod-
uct is fi lter-sterilized and fi lled into its fi nished product containers. The product is then freeze-
dried and the containers are subsequently sealed under vacuum, or are fl ushed with an inert gas
(e.g. N 2 ) before sealing. No preservative is added. The freeze-dried product is then stored below 8

C until shortly before its use.