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Subject: Factor VIII (Antihemophilic Factor)
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Factor VIII is synthesized in the liver and endothelial cells of other organs, including the spleen, which plays an important role in the synthesis of factor VIII. It is unaffected by liver failure or vitamin K deficiency.
It is the principal cofactor in the intrinsic pathway of coagulation and serves as a substrate for proteolysis by the proteins C/protein S complex.
PT (INR) is not affected by deficiency of factor VIII.
Most laboratories use a specific coagulant assay to measure factor VIII.
Chromogenic assays are also available.
Immunologic assays determine factor VIII antigen. The antigen is concordant to activity in most cases but may be normal occasionally in patients with a functional defect in the molecule.
Normal range: 70–150%.
Purified or recombinant factor VIII is used therapeutically for patients with hemophilia A.
Immunologic assays for factor VIII may be useful in the diagnosis of von Willebrand disease but are not necessary in the diagnosis of most cases of hemophilia.
If factor VIII decreases below 40%, PTT becomes prolonged. In the presence of an inhibitor to factor VIII, PTT remains prolonged even after therapeutic infusions of factor VIII; mixing the patient's plasma with normal plasma in a 1:1 proportion does not correct the prolonged PTT and does not increase the original low factor VIII. Specific methodology can report the titer of the inhibitor in Bethesda inhibitory units.
Hemophilia A: usually severe deficiency in male carriers and usually mild decrease in female carriers of the hemophilia gene
von Willebrand disease (see p. 454): especially if moderate to severe; more so in individuals with blood type B
Acquired anti–factor VIII autoantibodies in previously unaffected individuals
Acquired anti–factor VIII alloantibodies in hemophilia A patients treated with multiple infusions of factor VIII
DIC and pathologic fibrinolysis
Acute-phase reactant (acute inflammatory conditions).
Pregnancy and the use of oral contraceptives.
If markedly increased, it may predispose to thromboembolism.