Description of Human Coagulation Factor VIII

 Factor VIII (FVIII) is an indespensible blood clotting factor also known as anti-hemophilic factor (AHF). In humans, it is encoded by the F8 gene. Defects in this gene results in hemophilia A, a well known recessive X-linked coagulation disorder.

Factor VIII acts in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca⁺² and phospholipids forms a complex that converts factor X to the activated form Xa. The Factor VIII gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity.

Patients who have high levels of Factor VIII are at increased risk for deep venous thrombosis and pulmonary embolism.
FVIII generated from donated blood plasma (Aafact), or alternatively recombinant FVIII can be given to hemophiliacs to restore hemostasis.
The transfer of a plasma byproduct into the blood stream of a patient with hemophilia often gives to the transmission of diseases such as hepatitis B and C and HIV before purification methods were improved.
Antibody formation to Factor VIII can also be a major concern for patients receiving therapy against bleeding; the incidence of these inhibitors is dependent of various factors, including the Factor VIII product itself.

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