Biomedical Engineering Reference
In-Depth Information
vWF with equal affi nity to native VIII:C upon its injection into the patient's circulatory system.
Animal and human pharmacokinetic data reveal no signifi cant difference between the properties
of recombinant and native products.
Some patients, particularly those suffering from severe haemophilia A (i.e. those naturally pro-
ducing little or no VIII:C), will mount an immune response against injected factor VIII:C what-
ever its source.
The production of anti-factor VIII:C antibodies renders necessary administration of higher
therapeutic doses of the product. In severe cases, the product may even become ineffective. Sev-
eral approaches may be adopted in order to circumvent this problem. These include:
•
Exchange transfusion of whole blood. This will transiently decrease circulating anti-factor VIII:
C antibodies.
•
Direct administration of factor Xa, thus bypassing the non-functional step in the coagulation
cascade (Figures 12.2 and 12.3).
•
Administration of high levels of a mixture of clotting factors II, VII, IX and X, which works
effectively in 50 per cent of treated patients.
•
Administration of factor VIIa, as discussed subsequently.
•
Administration of porcine factor VIII, which may or may not cross-react with the antibodies
raised against human factor VIIIa. (However, the immune system will soon begin to produce
antibodies against the porcine clotting factor.)
•
Administration of factor VIII, with concurrent administration of immunosuppressive agents.
Owing to the frequency of product administration, the purifi cation procedure for recombinant
factor VIII:C must be particularly stringent. Unlike the situation pertaining when the product is
purifi ed from human blood, any contaminant present in the fi nal product will be non-human and,
hence, immunogenic. Sources of such contaminants would include:
•
host cell proteins;
•
animal cell culture medium;
•
antibody leaked from the immunoaffi nity column.
Emphasis is placed not only upon ensuring the absence of contaminant proteins, but also other
potential contaminants, particularly DNA. (Host cell-line-derived DNA could harbour oncogenes;
Chapter 7.)
Recombinant factor VIII is gaining an increasing market share of the factor VIII market.
Researchers are also attempting to develop modifi ed forms of VIII:C (by site-directed mutagen-
esis) that display additional desirable characteristics. Particularly attractive in this regard would
be the development of a product exhibiting an extended circulatory half-life. This could reduce
Search WWH ::
Custom Search