Clotting Cascade Case Study

Essay 112: Vitamin K and the Coagulation Cascade The human blood clotting cascade consists of a tightly regulated network of enzymes designed to contain damage to the blood vessels by means of coagulation, thus restoring vascular integrity. Briefly, when a blood vessel suffers penetrating trauma, blunt force trauma, or an internal rupture the clotting cascade swings into action. The various proteins activate one another culminating in the formation of a clot composed of a platelet plug and cross linked strands of fibrin. The clot, or thrombus, acts as damage control, stopping further loss of blood through the wound. Physiologists divide the clotting cascade into three branches: the extrinsic pathway, consisting of Factors III and

The best characterized of these disorders include deficiencies of Antithrombin III, Protein C, Protein S, and Factor V Leiden mutation. The treatment for these disorders is heparin injections in the acute setting. Long term treatment consists of anticoagulation with warfarin for patients with Protein C, S, or Factor V Leiden deficiency. People who are homozygous for Protein C deficiency require periodic transfusions of blood plasma rather than oral warfarin

This vitamin was designated "K" stemming from the German word for coagulation, or blood clotting. Although some Vitamin K is produced by intestinal bacteria, the majority is obtained from dietary sources. The human body requires this vitamin to produce functional blood clotting proteins, in particular Factor II (prothrombin), as well as Factors VII, IX, and X. Each of these proteins is a serine protease, an enzyme that cleaves certain peptide bonds in its target protein(s). As it turns out, these particular clotting factors must bind calcium in order to become fully activated. The ability to bind calcium, in turn, requires that these proteins undergo a modification at certain glutamate residues known as gamma carboxylation. The amino acid glutamate normally contains a single negatively charged COO-, or carboxylic acid group in its side chain. An additional COO- group allows glutamate to bind positively charged calcium ions much more effectively. Vitamin K is an essential cofactor in the enzymatic reaction producing gamma