Anticoagulants: Heparin

Anticoagulant medications are used to prevent blood clots from forming. These medications work by interfering with the normal function of plasma proteins called coagulation factors, which take part in secondary hemostasis-- where hemo refers to blood, and stasis meaning to halt or stop. In this video we’re going to focus on heparin, which works by indirectly inhibiting two clotting factors called thrombin and factor Xa by binding to and enhancing the activity of an anticoagulant protein called antithrombin III.

Now, before we discuss heparin in detail, we need to talk about the coagulation cascade, which is where heparin exerts its effect. The coagulation cascade begins via two pathways --the extrinsic and intrinsic pathways. The intrinsic pathway starts when circulating factor XII comes into contact with the surface of activated platelets or collagen. Activated factor XII, then activates factor XI, which activates factor IX which activates factor X. Factor Xa starts the common pathway where it activates factor II, or thrombin, which activates factor I that builds the fibrin mesh. When factor II gets activated it also activates 4 other factors: V, VIII, IX, and XIII. Factor V gets activated and acts as a cofactor for X, factor VIII acts as a cofactor for factor IX, and factor XIII helps factor I, or fibrin, form crosslinks. In the extrinsic pathway, exposed tissue factor activates factor VII, which activates factor X and starts the common pathway.

Now, the most important point of clot regulation is when a coagulation factor called thrombin is produced. Thrombin, or activated factor II, is a very important clotting factor, because it has multiple pro-coagulative functions. Think of thrombin as the accelerator on a car--the pedal that takes secondary hemostasis from 20 miles per hour to 100 miles per hour! First, thrombin binds to receptors on platelets causing them to activate. Activated platelets change their shape to form tentacle-like arms that allow them to stick to other platelets. Second, thrombin activates two cofactors; factor V used in the common pathway, and factor VIII used in the intrinsic pathway. Third, thrombin proteolytically cleaves fibrinogen or factor I, into fibrin or factor Ia which binds with other fibrin proteins to form a fibrin mesh. And finally, thrombin proteolytically cleaves stabilizing factor or factor XIII into factor XIIIa. Factor XIIIa combines with a calcium ion cofactor to form cross links between the fibrin chains, further reinforcing the fibrin mesh.