Hemostasis

Platelets are essential for many aspects of hemostasis, or the cessation of blood loss. Several substances are found within the cytoplasm of platelets that contribute to the arrest of bleeding as well as vessel repair  

These substances are discussed more fully in the following section. 

The prevention of blood loss from a damaged blood vessel is referred to as hemostasis. Three inherent mechanisms contribute to hemostasis  

Vascular constriction. The first mechanism to occur is vascular constriction. Immediately after a blood vessel is cut or severed, the vascular smooth muscle automatically constricts. This results in a decrease in the flow of blood through the vessel that helps to limit blood loss. The vasoconstriction is caused by several factors  

When the extent of the trauma to the vessel is increased, the degree of vascular constriction is increased. Accordingly, a sharply cut blood vessel bleeds far more profusely than a blood vessel damaged by a more crushing injury. The vasoconstriction may last for many minutes or hours, thus 

The glycosaminoglycans, sodium hyaluronate and chondroitin sulfate, bear structural resemblance to heparin. Several studies have demonstrated a slight an-ticoagulative effect of these materials (Pandolfi 8c Hedner, 1984). Viscoelastic substances work hemostatically which is caused predominantly through tamponade (Packer et al., 1985). 

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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. 

Factor Synthesis site Biologica I half-life, h Volume of distribution, MPV" Hemostasis concentratio 0/ n, % Per population Inheritanc d e pattern Chromoso me... 

The approximate concentration requited to produce hemostasis, in percent of normal concentration. 

S. S. Shapiro andM. Hultia, Semin. Thromb. Hemostasis 1, 336 (1975). 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

There are a number of tissue adhesives currently approved as adjuncts to hemostasis. Each agent has specific properties which enhance intraoperative hemostasis in particular situations. All forms of surgical bleeding are not alike. Bleeding can be fast or slow, diffuse or punctate, arterial or venous, capillary or larger vessel. Thus one agent may be more efficacious than another in a specific clinical situation. 

In 1998, the FDA approved fibrin sealant for three specific indications. These include hemostasis at the time of cardiac surgical operations [8] (Fig. 2) as well as at the time of operative procedures to treat splenic trauma. The application of the fibrin sealant which consists of normal biologic components in the body s clotting cascade creates a localized clot which further enhances inherent clotting ability. Although approved for these specific hemostatic indications only, fibrin sealant is useful as a hemostat in a wide variety of off-label clinical situations as well [9,10]. These include such applications as hemostasis for liver trauma or resection [11], vascular anastomoses [12], tonsillectomy [13], peripheral joint replacement [14], dental extractions [15], and bum debridement [16]. 

Fig. 2. Fibrin sealant spray application at site of left ventricular aneurysm repair to facilitate hemostasis (arrow points to adhesive).

Fig. 3. Collagen and thrombin gel applied to aehieve hemostasis at a vascular anastomosis (arrow points to gel).

The most extensive experience with tissue adhesive drug delivery exists in the fibrin sealant literature. This is clearly an off-label use of this agent as it is only currently approved for hemostasis in cardiac and splenic trauma surgery and for colon sealing at the time of colostomy closure. 

Chapman, W., Sherman, R., Boyce, S., Malawer, M., Hill, A., Buncke, G., Block, J., Fung, J., Clavien, R, Lee, K., Lebovic, G., Wren, S., Diethrich, E. and Goldstein, R., A novel collagen-based composite offers effective hemostasis for multiple surgical indications Results of a randomized controlled trial. Surgery, 129, 445-450 (2001). 

Platelets play an important role in hemostasis and are involved in the pathogenesis of many diseases, such as artherosclerosis and asthma. Moreover, an inadequately controlled aggregation may lead to vascular occlusion. 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

Platelets play a central role in primary hemostasis. They are also important in pathological processes leading to thrombosis. Antiplatelet drugs are primarily directed against platelets and inhibit platelet activation by a number of different mechanisms. They are used for the prevention and treatment of thrombotic processes, especially in the arterial vascular system. 

Bachmann F (1994) The plasminogen-plasmin enzym system. In Colman RW, Hirsh J, Marder VJ, Salzman EW (eds.) Hemostasis and thrombosis. Lippincott JB Comp., Philadelphia, pp 1592—1622... 

Furthermore, there is some evidence for pleiotrophic effects (e.g., effects on hemostasis, vascular function, anti-inflammatory effects, and stabilizing effects on atherosclerotic plaques) of statins. The clinical relevance of this (and the potential difference between the various statins) is at present uncertain but subject to intense investigation. 

Kleinschnitz C, Stoll G, Bendszus M et al (2006) Targeting coagulation Factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 203 513-518... 

One of the cell types involved in bone metabolism. In concert with osteoblasts, their cellular counterpart, these cells maintain bone hemostasis and constant... 

Platelets are the formed elements of the blood which participate in hemostasis. Platelets are enucleated, discoid fragments which arise from mature megakaryocytes in the bone marrow. Under normal circumstances, platelets do not adhere to endothelial surfaces of blood vessels. However, platelets can adhere to damaged areas of blood vessels and become activated in such a way that they can also bind fibrinogen. 

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