The normal hemostatic system consists of a complex process that limits blood loss by the formation of a platelet plug (primary hemostasis) and the production of cross-linked fibrin (secondary hemostasis), which strengthens the platelet plug. These reactions are counterregulated by the fibrinolytic system, which limits the size of fibrin clot that is formed, thereby preventing excessive clot formation. Congenital and acquired abnormalities occur in all these systems. The affected patients may have excessive hemorrhage, excessive thrombus formation, or both.
PRIMARY HEMOSTASIS Primary hemostasis is the platelet interaction with the vascular subendothelium that results in the formation of a platelet plug at the site of injury. Required components for this to occur are normal vascular subendothelium (collagen), functional platelets, normal von Willebrand factor (connects the platelet to the endothelium via glycoprotein Ib), and normal fibrinogen (connects the platelets to each other via glycoprotein II b-IIIa). FigureJJO-l depicts primary hemostasis
FIG. 210-1. Primary hemostasis. See text for details. vWF, von Willebrand factor; plt, platelet.
SECONDARY HEMOSTASIS Secondary hemostasis describes the reactions of the plasma coagulation proteins by a tightly regulated mechanism. The final product is cross-linked fibrin, which is insoluble and strengthens the platelet plug formed in primary hemostasis. Figure.,210-2. diagrams the reactions of secondary hemostasis.
FIG. 210-2. Secondary hemostasis, also known as the coagulation cascade. The unactivated coagulation proteins (factors) are indicated by roman numerals; after the reaction occurs, the factor is activated and designated by subscript A. There are two independent activation pathways. The contact system is known as the intrinsic pathway, and the tissue factor system is known as the extrinsic pathway. The pathways merge at the point of activation of factor X. This begins the common pathway that generates the final product, cross-linked fibrin. Ca2+, calcium; fibrinogen is factor I; PL, phospholipid surface (often platelets); prothrombin is factor II.
THE FIBRINOLYTIC SYSTEM This complex system regulates the hemostatic mechanism by limiting the size of fibrin clots that are formed. A simplified schema is depicted in Fig, 2.1.0.-3.. The principal physiologic activator is tissue plasminogen activator (tPA), which is released from endothelial cells. tPA converts plasminogen, which is synthesized in the liver and adsorbed in the fibrin clot, to plasmin. Plasmin degrades fibrinogen and fibrin monomer into low-molecular-weight fragments known as fibrin degradation products (FDPs) and cross-linked fibrin into D-dimers.
FIG. 210-3. The fibrinolytic pathway. See text for details. FDP, fibrin degradation product; tPA, tissue plasminogen activator.
Other physiologic inhibitors of hemostasis with prevalent clinical applicability include antithrombin III and the protein C-protein S system. Antithrombin III is a protein that forms complexes with all the serine protease coagulation factors (factors XII a, XIa, IXa, and thrombin), thereby inhibiting their function. Heparin potentiates this interaction, and this is the basis for its use as an anticoagulant. Protein C, which requires the presence of protein S for activation, is capable of inactivating the two plasma cofactors, factors V and VIII, and inhibiting their participation in the coagulation cascade.
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