Elevated Procoagulants and Their Effects

High levels of other procoagulants such as factors VII, VIII, IX, XI, VII, fibrinogen, and von Willebrand factor are associated with an increased risk of clotting. Specifically, high levels of FVIII over time have been shown to be associated with repeat blood clots.

ELEVATED FACTOR VII LEVELS

Some studies have shown an increased risk of heart disease with high levels of coagulation factor VII. FVII levels, however, are not a single risk factor after controlling for cholesterol, LDL-cholesterol, and triglycerides. Elevated FVII levels have been reported in people with blockage of a retinal (eye) vein.

ELEVATED FACTOR VIII LEVELS

Coagulation factor VIII activity levels may vary widely due to various reasons, such as:

  • Pregnancy

  • Use of hormonal therapy

  • Stress

  • Exercise

  • Presence of an inflammatory state

A high level of FVIII is a known independent risk factor for blood clotting. High levels of FVIII are an even stronger risk factor for repeat blood clots. The likelihood of a second clotting event within two years of the first clot was found to be 37% in people with a high FVIII level versus 5% among persons with a lower FVIII level.

ELEVATED FACTOR XI LEVELS

High levels of coagulation factor IX may play a role in the risk of developing a blood clot. The Leiden Thrombophilia Study found that levels of FIX in the 90th percentile and higher increased the risk of blood clots by two- to three-fold.

ELEVATED FACTOR XI LEVELS

Coagulation factor XI plays two roles in blood clotting. FXI contributes to the formation of fibrin (which is one of the main components of a clot). It also protects the fibrin that has formed from being broken down.

People with high FXI levels have an increased risk of a blood clot in a deep vein, such as a vein in the leg. The higher the FXI level, the greater the risk of a blood clot. Increased levels of FXI also have been associated with an increased risk of heart disease in women.

ELEVATED VON WILLEBRAND FACTOR LEVELS

Von Willebrand factor (VWF) is produced in cells that line the blood vessels (the endothelium). Damage to or swelling of this blood vessel lining leads to increased Von Willebrand factor levels. FVIII circulates with Von Willebrand factor, and often the levels of these two clotting factors are similarly affected by stress, inflammatory states, or endothelial injury.

Continuously high levels of FVIII lead to an increased risk of blood clots; therefore it might be reasonable to assume that elevated levels of Von Willebrand factor would also be associated with and contribute to an increased risk of clots. Additionally, Von Willebrand factor plays an important role in platelet adhesion (platelet stickiness) to the damaged blood vessel lining.