Factor VIII

Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by F8 gene.^[5][6] Defects in this gene result in hemophilia A, an X-linked bleeding disorder.^[7]

Factor VIII is produced in the liver's sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to a plasma carrier (another protein) called von Willebrand factor, until an injury that damages blood vessels occurs.^[8] In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts (by an as-yet-unknown mechanism) with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.^[8]

Factor VIII participates in blood coagulation; it is a cofactor for factor IXa, which, in the presence of Ca²⁺ 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.^[9]

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism.^[10] Copper is a required cofactor for factor VIII and copper deficiency is known to increase the activity of factor VIII.^[11]

Factor VIII is available as a medication that is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[12]