FaktorVIII

Factor VIII, also known as antihemophilic factor, is a coagulation protein that functions in the intrinsic pathway of blood clotting. In plasma it circulates bound to von Willebrand factor (VWF), which stabilizes FVIII and protects it from degradation. FVIII is produced mainly by liver sinusoidal endothelial cells and is secreted as a large glycoprotein that, after activation, becomes Factor VIIIa, a calcium-dependent cofactor.

FVIII participates in the tenase complex with activated factor IX (FIXa) on phospholipid surfaces: FVIIIa coauthenticates FIXa to convert factor X to Xa, accelerating thrombin generation and fibrin clot formation. The activation of FVIII to FVIIIa is mediated by thrombin (and to some extent factor Xa) and requires cleavage at several sites.

Genetics: The F8 gene (Xq28) encodes FVIII. It is inherited in an X-linked recessive manner; males are predominantly affected, while many female carriers remain asymptomatic or mildly affected. Severe deficiency (<1% of normal activity) causes classic hemophilia A; milder forms have residual FVIII activity.

Clinical: Patients have spontaneous joint and muscle bleeds, and a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT). Diagnosis uses factor activity assays and mixing studies. Inhibitors to FVIII (alloantibodies) occur in a subset of patients and complicate therapy.

Treatment: FVIII replacement therapy with plasma-derived or recombinant products is the mainstay. Desmopressin (DDAVP) raises endogenous FVIII levels in some mild cases. Prophylactic regimens reduce bleeding. Inhibitors may be treated with immune tolerance induction or bypassing agents; gene therapy is under development.