the stoppage of bleeding, is accomplished through three steps:
- A vascular spasm, a constriction of the damaged blood vessel, occurs at the site of injury. Vasoconstriction is initiated by the smooth muscle of the blood vessel in response to the injury and by nerve signals from pain receptors.
- A platelet plug, consisting of a mass of linked platelets, fills the hole in the damaged blood vessel. Platelet plug formation follows these steps:
Platelet adhesion. Platelets adhere to the exposed collagen fibers in the damaged blood vessel wall.
Platelets release ADP (adenosine diphosphate, which attracts other platelets to the injury), serotonin (which stimulates vasoconstriction), and thromboxane A 2 (which attracts platelets and stimulates vasoconstriction, and keeps the platelets “sticky” so they continue to adhere to the injured site). Cellular extensions from the platelets interconnect and form a loose mesh. Aspirin inhibits the formation of clots because aspirin prevents the formation of thromboxane A 2.
Platelet aggregation. Additional platelets arrive at the site of the injury in response to the released ADP and expand the accumulation of platelets.
Figure 1. The Clotting Process
Coagulation (blood clotting) is a complex series of reactions that transform liquid blood into a gel (clot), providing a secure patch to the injured blood vessel. Thirteen coagulation factors (numbered I through XIII in order of their discovery) are involved. Most of these factors are proteins released into the blood by the liver. Factor IV is Ca 2+. Vitamin K is required for the synthesis of some of these factors. The coagulation process can be described in three major steps:
Formation of factor X and prothrombinase. Prothrombinase (prothrombin activator) can form either intrinsically (inside the blood vessels) or extrinsically (outside the blood vessels). In the intrinsic pathway, the collagen of the damaged blood vessel initiates a cascade of reactions that activate factor X. In the extrinsic pathway, damaged tissues release thromboplastin (tissue factor, TF), which initiates a shorter and more rapid sequence of reactions to activate factor X. In both pathways, activated factor X combines with factor V (with Ca 2+ present) to form prothrombinase.
Prothrombin is converted to thrombin. In this common pathway that follows both the intrinsic and extrinsic pathways, prothrombinase (with Ca 2+) converts prothrombin to thrombin.
Fibrinogen is converted to fibrin. The common pathway continues as thrombin (with Ca 2+) converts fibrinogen to fibrin. Fibrin forms long strands that bind the platelets together to form a dense web. Thrombin also activates factor XIII, which helps fibrin strands cohere to one another. The result is a clot. See Figure 1.
Following its formation, a clot is further strengthened by a process called clot retraction. Platelets in the clot contract, pulling on the fibrin strands to which they are attached. The result is a more tightly sealed patch.
Fibrinolysis is the breakdown of the clot as the damaged blood vessel is repaired. During the formation of a clot, the plasma protein plasminogen is incorporated into the clot. The healthy endothelial tissue that replaces the damaged areas of the blood vessel secretes tissue plasminogen activator (t‐PA), which converts plasminogen into its active form, plasmin (fibrinolysin). Plasmin in turn breaks down fibrin and leads to the dissolution of the clot.