Key:

Black arrows = activation

Red arrows = inactivation

APC = activated protein C

TM = thrombomodulin, a protein bound to endothelial cell membranes to which protein C binds

PL = phospholipid

Ca²⁺ = calcium

Each reaction in the coagulation cascade involves the conversion of a clotting factor precursor into an active protease by proteolysis, regulated by cofactors and calcium. The end point is the generation of enough thrombin to catalyze the formation of fibrin, which then polymerizes and crosslinks to form a clot. Under pathological conditions, the mutation in factor V renders it resistant to inactivation by APC. Hence mutated factor V pushes the cascade towards excessive blood clot formation. Mutations in the upstream region of the prothrombin gene result in increased levels of prothrombin in the blood, again encouraging the formation of a thrombus. Protein C, protein S and antithrombin III all have anti-coagulant action. Deficiencies of proteins C and S usually result in a syndrome of recurrent venous thrombosis and pulmonary embolism. Deficiency of antithrombin III is usually mild.