Blood clot hemostasis

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

Platelets play a role in each of the mechanisms of normal hemostasis vasoconstriction, formation of the platelet plug, and blood coagulation. However, they are also involved in pathological processes that lead to atherosclerosis and thrombosis (formation of a blood clot within the vascular system). Antiplatelet drugs interfere with platelet function and are used to prevent the development of atherosclerosis and formation of arterial thrombi. 

Blood coagulation. The third major step in hemostasis is coagulation, or the formation of a blood clot. This complex process involves a series of reactions that result in formation of a protein fiber meshwork that stabilizes the platelet plug. Three essential steps lead to clotting (see Figure 16.1) ... 

Self-protection. To prevent blood loss when a vessel is injured, the blood has systems for stanching blood flow and coagulating the blood (hemostasis see p. 290). The dissolution of blood clots (fibrinolysis) is also managed by the blood itself (see p. 292). 

Following injury to blood vessels, hemostasis ensures that blood loss is minimized. Initially, thrombocyte activation leads to contraction of the injured vessel and the formation of a loose clot consisting of thrombocytes (hemostasis). Slightly later, the action of the enzyme thrombin leads to the formation and deposition in the thrombus of polymeric fibrin (coagulation, blood clotting). The coagulation process is discussed here in detail. 

Little intravascular coagulation of blood occurs in normal physiological conditions. Hemostasis involves the interplay of three procoagulant phases vascular, platelet, and coagulation) that promote blood clotting to prevent blood loss (Fig. 22.1). The fibrinolytic system prevents propagation of clotting beyond the site of vascular injury and is involved in clot dissolution, or lysis (Fig. 22.2). 

Hemostasis is the process of blood clot formation at the site of vessel injury. When a blood vessel wall breaks, the hemostatic response must be rapid, localized, and carefully regulated. Abnormal bleeding or a propensity to nonphysiologic thrombosis (i.e., thrombosis not required for hemostatic regulation) may occur when specific elements of these processes are missing or dysfunctional. The elements responsible for normal hemostasis have received extensive review. 

To maintain hemostasis, blood must be retained in the vasculature as fluid. At the same time, blood components must be able to respond rapidly with a clot when a vascular injury occurs. To repair a vascular injury, platelets in blood first adhere as aggregates to the endothelial cells at the affected site and form an initial blood clot. Platelets then stimulate and activate coagulation factors found in plasma to form a more stable fibrin clot. As the injury is resolved and healed, the clot is degraded. Thrombosis is a pathological event wherein a blood clot occludes a blood vessel, resulting in ischemic necrosis of the tissue fed by the blood vessel. Ischemic necrosis involves local anemia and oxygen deprivation. Thrombosis of a coronary artery may lead to myocardial infarction or unstable angina [20]. 

To understand how various drugs affect hemostasis, it is necessary to review the normal way in which blood clots are formed. The physiologic mechanisms involved in hemostasis are outlined in Figure 25-1, with... 

Normal hemostasis is a balance between excessive and inadequate blood clotting. Overactive blood clotting is harmful because of the tendency for thrombus formation and occlusion of arteries and veins. Vessels may become directly blocked by the thrombus, or a portion of the thrombus may break off and create an embolism that lodges elsewhere in the vascular system. The tendency for excessive thrombus formation in the venous system is usually treated with anticoagulant drugs such as heparin and warfarin. Platelet inhibitors such as aspirin help prevent arterial thrombogenesis. Thrombolytic drugs (streptokinase, t-PA) that facilitate the dissolution of harmful clots may successfully reopen... 

Enzyme inhibition is one of the ways in which enzyme activity is regulated experimentally or naturally. Most therapeutic drugs function by inhibition of a specific enzyme. Inhibitor studies have contributed much of the available information about enzyme kinetics and mechanisms. In the body, some of the processes controlled by enzyme inhibition are blood coagulation (hemostasis), blood clot dissolution (fibrinolysis), complement activation, connective tissue turnover, and inflammatory reactions. 

Blood normally circulates through endothelium-lined blood vessels. When a blood vessel is severed, a blood clot (called a thrombus, which is formed by the process of thrombosis) forms as part of hemostasis, the physiologic response that stops bleeding. Blood clots also form to repair damage to the endothelial lining, in which components of the subendothelial layer become accessible to plasma proteins. 

Whereas tiie anticoagulants prevent tlirombus formation, tiirombolytic dru dissolve blood clots tiiat have already fonned witiiin tiie walls of a blood vessel. These dni reopen blood vessels after they become occluded. Anotiier tenn used to identify tiie tiirom-bo lytic drugs is fibrolytic drugs. Each of tiiese groups of dni is discussed in tiiis chapter. Before tiiese dru are discussed, a basic understanding of hemostasis and tlirombus fonnatioii is needed. 

The adsorption of proteins is the first interaction which occurs when a foreign surface comes in contact with blood. The processes which then lead to hemostasis are attachment of cellular elements to the surface, platelet adhesion and release, and triggering of the blood coagulation cascade. Investigations of interactions of proteins at the interface, which are the primary steps in blood clotting and determine whether it will occur, are hence of fundamental importance. 

Whole blood is seldom used ia modem blood transfusion. Blood is separated into its components. Transfusion therapy optimizes the use of the blood components, using each for a specific need. Red cell concentrates are used for patients needing oxygen transport, platelets are used for hemostasis, and plasma is used as a volume expander or a source of proteins needed for clotting of the blood. 

Each component of blood has a function ia the body. Red cells transport oxygen and carbon dioxide between the lungs and cells ia the tissues. White cells function as defense of the body. Platelets are important for hemostasis, ie, the maintenance of vascular iategrity. Plasma, an aqueous solution containing various proteias and fatty acids, transports cells, food, and hormones throughout the body. Some proteias ia plasma play a role ia clotting, others are messengers between cells. 

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