Factor V Leiden

Factor V Leiden is a disorder where blood clots form more easily due to a mutation in a clotting protein called factor V. Factor V Leiden is the most common hypercoagulable disorder in people of caucasian descent, and was named after the town Leiden in Holland, where the disease was first described.

Now, Factor V Leiden is a hemostasis disorder.

Hemostasis is the process where blood flow is stopped after there’s damage to a blood vessel, and it has two steps.

Primary hemostasis involves the formation of a platelet plug at the site of injury, and secondary hemostasis involves the coagulation cascade, where several clotting factors come into play to form a fibrin mesh over the platelet plug to reinforce it - forming a blood clot.

Hemostasis can be both stimulated, and inhibited by several factors.

One way to stimulate hemostasis is with thrombin, or factor II, which increases platelet activation, and cleaves several factors involved in secondary hemostasis to their active form.

So one way to inhibit hemostasis is actually to inhibit thrombin.

This happens with the help of anticoagulant proteins like protein C. Protein C is a vitamin K dependent circulating plasma protein produced in the liver along with a cofactor called protein S.

Both protein C and S interact with a protein called thrombomodulin, which is on the surface of intact endothelial cells that line our blood vessels.

So, let’s say you cut your finger and now a blood clot has formed.

When there’s a lot of thrombin around a damaged blood vessel, excess thrombin binds to thrombomodulin and it can no longer participate in the coagulation cascade.

So in a sense, the undamaged cells help ensure that the coagulation process is limited to the injury site.

Furthermore, the thrombin-thrombomodulin complex binds to protein C. Protein S then joins the party, forming a complex that includes protein C, protein S, and thrombin-thrombomodulin. Protein S binding to this complex activates the proteolytic site of protein C which then cleaves and inactivates active factor V, which is a cofactor for factor X in the common pathway of the coagulation cascade, as well as factor VIII, which is a cofactor for factor IX in the intrinsic pathway of the coagulation cascade.