ANATOMY & PHYSIOLOGY The stimulus for clotting is a rough surface within a vessel, or a break in the vessel, which

also creates a rough surface. The more damage there is, the faster clotting begins, usually within 15 to 120 seconds. The clotting mechanism is a series of reactions involving chemicals that normally circulate in the blood and others that are released when a vessel is damaged. The chemicals involved in clotting include platelet factors, chemicals released by damaged tissues, calcium ions, and the plasma proteins prothrombin, fibrinogen,Factor 8, and others synthesized by the liver. (These clotting factors are also designated by Roman numerals; Factor 8 would be Factor VIII.) Vitamin K is necessary for the liver to synthesize prothrombin and several other clotting factors (Factors 7, 9, and 10). Most of our vitamin K is produced by the bacteria that live in the colon; the vitamin is absorbed as the colon absorbs water and may be stored in the liver. Chemical clotting is usually described in three stages, Stage 1 begins when a vessel is cut or damaged internally, and includes all of the factors shown. As you follow the pathway, notice that the product of stage 1 is prothrombin activator, which may also be called prothrombinase. Each name tells us something. The first name suggests that this chemical activates prothrombin, and that is true. The second name ends in ase, which indicates that this is an enzyme. The traditional names for enzymes use the substrate of the enzyme as the first part of the name, and add ase. So this chemical must be an enzyme whose substrate is prothrombin, and that is also true. The stages of clotting may be called a cascade, where one leads to the next, as inevitable as water flowing downhill. Prothrombin activator, the product of stage 1, brings about the stage 2 reaction: converting prothrombin to thrombin. The product of stage 2, thrombin, brings about the stage 3 reaction: converting fibrinogen to fibrin (see Box 11 6: Hemophilia). The clot itself is made of fibrin, the product of stage 3. Fibrin is a thread-like protein. Many strandsof fibrin form a mesh that traps RBCs and platelets,and creates a wall across the break in the vessel. Once the clot has formed and bleeding has stopped,clot retraction and fibrinolysis occur. Clot retraction requires platelets, ATP, and Factor 13 and involvesfolding of the fibrin threads to pull the edges of the rupture in the vessel wall closer together. This willmake the area to be repaired smaller. The platelets contribute in yet another way, because as they disintegratethey release platelet-derived growth factor (PDGF), which stimulates the repair of blood vessels (growth of their tissues). As repair begins, the clot is dissolved, a process called fibrinolysis. It is important that the clot be dissolved, because it is a rough surface, and if it were inside a vessel it would stimulate more and unnecessary clotting, which might eventually obstruct blood flow.