CLINICAL ASPECTS OF CLOTTINGCZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY (,&
Figure 13.27 Structures of the clotting inhibitors
(A) dicoumarol and (B) warfarin.CHCH 3CH 2CH 2COO
OHOHOOO OHOOA)B)inhibitors of this process. Dicoumarol was first discovered in spoiled sweet
clover because it causes fatal hemorrhages in cattle, and warfarin was originally
developed as rat poison. Agents such as warfarin are used for anticoagulant
therapy. They are slow to produce effects but they have long plasma half-lives
and so can be active for days (Chapter 14).
Hemophilia
The bleeding disease, hemophilia, is caused by a genetic lack of clotting
factors. In these disorders, the bleeding time is normal but the clotting (or
coagulation) time prolonged. The symptoms are a tendency for hemorrhages,
that is blood loss, either spontaneous or from even small injuries. Some
patients with hemophilia A may have a normal prothrombin time because
their concentration of tissue factor is high. The commonest of the hemophilias
is hemophilia A, in which Factor VIII is deficient. In north America, about 80%
of the cases are hemophilia A. This deficiency is sex-linked to males, with a
frequency of about one in 5000 to 10 000. The plasma levels of Factor VIII in
patients with severe hemophilia A are less than 5% of normal. Hemophilia
B, the second commonest form of hemophilia, is due to a lack of Factor IX.
Factor IX is also called Christmas Factor because it was first found to be
missing in a patient named Stephen Christmas.
In the past, hemophilias were treated by blood transfusion. However, repeated
transfusion brings the possibility of infection with HIV or hepatitis, as well
as the possibility of immune reactions and iron overload. Initial treatments
involved purifying the factor from human plasma obtained from pooled blood.
Modern treatment involves injections of Factor VIII prepared by recombinant
DNA technology. This eliminates any chance of infection but is expensive. The
same treatments are applicable to hemophilia B.