Factor VIII

Factor VIII acts an as accelerator in the activation of Factor X by Factor IXa. It is activated by trace amounts of thrombin and subsequently downregulated through inactivation by activated protein C. In the circulation factor VIII is bound by von Willebrand factor, which protects the factor VIII from proteolysis. the circulating half-life of factor VIII is 8 – 12 hours. Although apparently not necessary for initial thrombin generation, Factor VIII seems to be essential for subsequent propagation of the fibrin clot.

Congenital FVIII deficiency (Hemophilia A) is associated with a lifelong bleeding disorder, the severity of which is directly related to the FVIII level in the plasma. Hemophilia A is transmitted genetically as an X-linked recessive disorder affecting males whose daughters and mothers are obligate carriers of the defective gene. Exceptions to this can occur in females with Turner’s syndrome, homozygous female progeny of hemophiliac carriers and affected males, and when there is variable expressivity of factor VIII alleles on the X chromosome (lyonization) in female carriers. In about 30% of cases there is no prior family history of the disorder and the condition is a result of a spontaneous mutation.

The most common sites of bleeding in severe hemophilia involve joints and muscles. Recurrent bleeding into the joints can eventually cause chronic swelling and joint deformity. Other types of bleeding include intramuscular, intracranial/intracerebral, gastrointestinal and in the urinary tract.

Assays of the coagulation factors are functional measurements of the individual clotting proteins. They are measured by testing the ability of the patient's plasma to correct the clot time of a plasma known to be completely deficient in the clotting factor under test. By comparing the degree of correction with dilutions of a normal plasma, the actual clotting factor level of the test plasma can be calculated. Factor assays are either based on the Prothrombin Time (Factors II, V, VII and X) or the APTT (Factors VIII, IX, XI and XII).

In the Hemostasis and Thrombosis Laboratory, the normal range for FVIII is 70 - 150%.

Less common causes of severe Factor VIII deficiency occur in patients with von Willebrand disease type 2N (Normandy) and type 3, and in patients who develop autoantibodies to factor VIII (acquired factor VIII inhibitor). Mild reductions of factor VIII may be seen in patients with Type 1 von Willebrand disease and some with Type 2 von Willebrand disease and potentially in patients receiving Xigris.