Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

U N I T 3

with a surface coat of glycocalyx, consisting of glycopro- teins, glycosaminoglycans, and several coagulation fac- tors adsorbed from the plasma. 2 One of the important glycoproteins is glycoprotein IIb/IIIa (gpIIb/IIIa), which binds fibrinogen (factor I) and acts to connect platelets together to form large aggregates. Phospholipids, which are also present in the platelet membrane, provide criti- cal binding sites for calcium and coagulation factors in the intrinsic coagulation pathway. 2,3 The cell mem- brane is supported by a network of microtubules, actin filaments, myosin, and actin-binding proteins. They are arranged circumferentially and are responsible for maintaining the platelet’s disk shape. The central part of the platelet contains mitochon- dria, enzymes needed for synthesis of adenosine tri- phosphate (ATP) and the prostaglandin thromboxane A 2 (TXA 2 ), glycogen, and two specific types of granules ( α - and δ -granules) that release mediators for hemosta- sis. 2–5 The α -granules contain fibrinogen, coagulation factors, plasminogen, plasminogen activator inhibitor, and platelet-derived growth factors. The contents of these granules play an important role in platelet aggre- gation, blood coagulation, and the initial phase of ves- sel repair. The release of growth factors causes vascular endothelial cells, smooth muscle cells, and fibroblasts to proliferate and grow. The δ -granules, or dense granules, mainly contain adenosine diphosphate (ADP), ATP, ion- ized calcium, serotonin, and histamine, which facilitate platelet adhesion and vasoconstriction at the site of ves- sel injury. The Coagulation System The coagulation system uses plasma proteins that are present as inactive procoagulation factors. Each of the procoagulation or coagulation factors, identified by Roman numerals, performs a specific step in the coagu- lation process. The activation of one procoagulant or proenzyme is designed to activate the next factor in the sequence (i.e., cascade effect). Because most of the inac- tive procoagulants are present in the blood at all times, the multistep process ensures that a massive episode of intravascular clotting does not occur by chance. It also means that abnormalities of the clotting process occur when one or more of the factors are deficient or when conditions lead to inappropriate activation of any of the steps. Most of the coagulation factors are proteins synthe- sized in the liver. Vitamin K is necessary for the synthe- sis of factors VII, IX, and X; prothrombin (factor II); and proteins C and S. Calcium (factor IV) is required in all but the first two steps of the clotting process. The body usually has sufficient amounts of calcium for these reactions. Inactivation of the calcium ion prevents blood from clotting once removed from the body. The addition of citrate to blood stored for transfusion purposes pre- vents clotting by chelating ionized calcium. A clot is not expected to be a permanent solution to vessel injury; thus, blood clotting is accompanied by processes designed to control the coagulation cascade and dissolve the clot once bleeding has been controlled.

called thrombopoietin that causes proliferation and maturation of megakaryocytes. 2 Thrombopoietin is produced in the liver, kidney, smooth muscle, and bone marrow. Its production and release are regulated by the number of platelets in the circulation. Although platelets lack a nucleus, they have many of the structural and functional characteristics of a whole cell. 1–5 They contain an outer cell membrane, microtu- bular structures, and inner organelles (Fig. 12-2). The platelet cell membrane, which plays an important role in platelet adhesion and the coagulation process, is covered FIGURE 12-1. A scanning electron micrograph depicting a number of red cells enmeshed in a fibrinous matrix on the luminal surface of an indwelling catheter (magnification × 5698). (From the Centers for Disease Control and Prevention Public Health Images Library No. 7313. Courtesy of Janice Carr.)

GPIIb/IIIa glycoprotein

Glycocalyx coat

Plasma membrane

Glycogen

Actin Myosin II

α -Granules

δ -Granules

Mitochondria

Microtubules

FIGURE 12-2. Platelet structure.