Factor VIII

Functions as a cofactor to factor IXa in the tenase complex, and a deficiency of factor VIII thus reduces the generation of thrombin on the surface of activated platelets.

Synthesized as a 330-kDa precursor protein with an A1-a1-A2-a2-B-a3-A3-C1-C2 domain structure.

FVIII associates with von Willebrand Factor (vWF) in heterodimers of a heavy (A1-a1-A2-a2) and a light (a3-A3-C1-C2) chain associated by a metal ion interaction.

A unit of Factor VIII refers to the amount of Factor VIII present in 1 ml of normal plasma.

Von Willebrand factor has a limited natural half-life and stabilizes factor VIII  by binding to it in the circulation.

This effect causes a ceiling effect and limits the half life extension of factor VIII TO approximately 18 hours.

Labile protein and assays should be performed on fresh plasma samples.

Frozen sample analysis may result in loss of factor VIII activity of 10-20%.

von Willebrand factor is a carrier protein for factor VIII, thus reduced factor VIII activity should prompt an analysis of von Willebrand factor to exclude the presence of von Willebrand disease.

There is a 6 fold increase in the rate of recurrent thromboses with elevated factor VIII plasma levels.

Term infants have increased hematocrit levels in the umbilical cord which can underestimate factor VIII activity.

Elevated factor VIII activity may be seen in thrombophilia.

Persistently elevated factor VIII of levels greater than 150% of normal, associated with a 2-11 fold increased risk of VTE.

Factor VIII levels are genetically determined, and patients with type A or B blood have factor VIII levels 22% higher than those patients with type O blood.

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