Hemostasis

Hemostasis

The stoppage of bleeding is known as hemostasis. When blood vessels are damaged, this vital process helps to limit or prevent blood loss. It involves several­ steps, including blood vessel spasms, the formation­ of a platelet plug, and coagulation of the blood.

The process­ of hemostasis is quick and localized, involving a variety of clotting factors from the plasma, along with substances released by platelets and injured tissue cells. The three steps of hemostasis are vaso-spasm or vascular spasm, platelet plug formation, and coagulation (blood clotting). After hemostasis, theclot retracts and eventually dissolves to be replaced by fibrous tissue that prevents any additional blood loss.

Step 1: Vasospasm

When a smaller blood vessel is cut or broken, smooth muscles in its walls contract, which is known as vaso-spasm, and loss of blood slows nearly immediately. Avasospasm has the potential to completely close the ends of a severed vessel. The vascular spasm lasts for approximately 30 minutes and is also known as the vas-cular phase of hemostasis. The endothelial cells ­contractto expose the basement membrane to the bloodstream.

Chemical factors and local hormones begin to be released by the endothelial cells. Also released are endothelins, which are peptide hormones that stimu-late smooth muscle contraction and promote vascular spasms. They also stimulate endothelial cell division, smooth muscle cell division, and fibroblast division to accelerate repair of damaged tissue.

Step 2: Platelet Plug Formation

In the platelet phase, a platelet plug forms because of platelet aggregation, and blood begins coagulating (FIGURE 17-9). Platelets release serotonin to contract smooth muscles in blood vessels, reducing blood loss. In platelet adhesion, the platelets stick to rough sur-faces and connective tissue collagen under the endo-thelial blood vessel lining. They also stick to each other to form a platelet plug in the area of the blood vessel injury. Larger breaks may require a blood clot to stop bleeding. The growth of the platelet plug is limited by several following important factors:

■■ The endothelial cells release a prostaglandin known as prostacyclin, which inhibits platelet aggregation.

■■ White blood cells entering the area release inhibitory compounds.

■■ Adenosine diphosphate near the platelet plug is broken down by circulating plasma enzymes.

■■ Compounds such as serotonin inhibit platelet plug formation once they are present in high quantities.

■■ The development of a blood clot strengthens the platelet plug but isolates the platelet plug from the general circulation.

Step 3: Coagulation

The formation of a blood clot is known as coagulation. The coagulation phase requires many biochemicals known as clotting factors or procoagulants. They are synthesized by the liver. Some clotting factors promote coagulation, whereas others inhibit it, so a delicate balance between these two types is achieved to address the specific injured tissue (TABLE 17 -3). Many present proteins or proenzymes control vital reactions in the clotting response. Calcium ions and vitamin K are very important for nearly all of the coagulation process. Adequate amounts of vitamin K must be present in the liver for it to synthesize prothrombin and other clotting factors.

The most important event in coagulation is the conversion of the plasma protein fibrinogen into the insoluble threads of the protein called fibrin. The first step is the release of tissue thromboplastin, which results in the production of prothrombin activator. FIGURE 17-10 describes the blood-clotting cascade.

The three pathways to the activation of the clot-ting system are the extrinsic pathway, the intrinsicpathway,and the common pathway. When dam-aged endothelial cells or peripheral tissues release Factor­ III ortissue factor, the extrinsic pathwaybegins. Tissue factor combines with calcium ions and Factor VII, forming an enzyme complex that is able to activate Factor X, which is the first stage of the common­ pathway. The intrinsic pathway starts with activation of proenzymes, primarily Factor XII, exposed to collagen­ fibers at the site of injury. A plate-let factor known as PF-3 assists the process. Other factors speed up the reactions in this pathway, and eventually, activated Factor VIII and Factor IX com-bine, forming an enzyme complex that can activate Factor X. The common pathway begins as the enzyme prothrombinase is formed.

Prothrombin is an alpha globulin made in theliver on a continual basis and is always present in the blood plasma. Prothrombinase converts prothrom-bin into thrombin, which causes fibrinogen to be cut into sections of fibrin. This fibrin then joins to form long threads. The threads stick to surfaces of damaged blood vessels to create a mesh that traps blood cells and platelets. The result is a blood clot. A clear, yellowish liquid remains after formation of the clot. This liquid is called serum and is plasma minus its clotting factors.

More prothrombinase becomes present if tissue damage is more severe. Continual clotting occurs to stop greater damage. Positive feedback is used to stimulate more clotting action based on the original clotting action. However, this continual process can only work for a short time because it interrupts the stability of the body’s internal environment. Excess thrombin is normally carried away to avoid the for-mation of a massive blood clot. As a result, blood coagulation usually occurs in blood that is not mov-ing or only moving slowly. Clotting stops where a clot contacts the circulating blood.

Blood clots in ruptured vessels are invaded by fibroblasts to produce fibrous connective tissue that helps seal blood vessel breaks. Clots that form in ­tissues as a result of blood leakage are called ­hematomas, which disappear over time. This process requires the plasma protein plasminogen to be converted to ­plasmin, an enzyme that digests threads of fibrin and other proteins involved in clotting. Although plasmin may dissolve entire clots, those that fill large blood vessels usually are not removed naturally. Plasmin is also called fibrinolysin.

Substances that Control Coagulation

Certain substances deactivate or remove clotting factors as well as other stimulatory agents from the blood to control coagulation. Examples of these substances include plasma anticoagulants such as antithrombin III; heparin, which is the naturalanticoagulant released by basophils and mast cells; aspirin ; thrombomodulin, which is released by endo-thelial cells, binds to thrombin, and converts it to an enzyme that activates protein­C , which inacti-vates clotting factors and helps to form plasmin; prostacyclin, which inhibits platelet aggregationand opposes thrombin and adenosine diphosphate; alpha-2 -macroglobulin, which inhibits thrombin;and C1 inactivator, which inhibits several intrinsic clotting factors.

Retraction of the Clot

Syneresis is also known asclot retraction, in whichthe torn edges of a damaged vessel are pulled closer together. This reduces bleeding and stabilizes the site of injury. It also reduces the size of the area of damage, so that fibrocytes, endothelial cells, and smooth mus-cle cells can continue the repair process.

Fibrinolysis

Over time, the clot dissolves as fibrinolysis starts by activation of plasminogen by thrombin as well as tis-sue plasminogen activator. This activator is releasedby damaged tissues at the injury site. Plasminogen then leads to production of plasmin, the enzyme that begins digestion of the fibrin strands and erosion of the clot.

1. What is the difference between a thrombus and an embolus?

2. List the major steps involved in blood clot formation.

3. Define the terms hemostasis, vasospasm, and prothrombin.

4. Identify the three pathways to the activation of the clotting system.