Clot stabilization and resorption. Polymerized fibrin and platelet aggregates undergo contraction to form a solid, permanent plug that prevents further hemorrhage. At this stage, counterregulatory mechanisms (e.g., tissue plasminogen activator, t-PA made by endothelial cells) are set into motion that limit clotting to the site of injury (
Fig. 4.5D ) and eventually lead to clot resorption and tissue repair.
http://ebooksmedicine.net 102CHAPTER 4 Hemodynamic Disorders, Thromboembolism, and Shock
A. VASOCONSTRICTION
Site of injury
B. PLATELET ACTIVATION AND AGGREGATION 2 Shape change 4 Recruitment 3 Granule release (ADP, TXA2)
C. ACTIVATION OF CLOTTING FACTORS AND FORMATION OF FIBRIN
D. CLOT RESORPTION Trapped neutrophilExpression of:
Fig. 4.5 Normal hemostasis. (A) After vascular injury, local neurohumoral factors induce a transient vasoconstriction. (B) Platelets bind via glycoprotein Ib (GpIb) receptors to von Willebrand factor (VWF) on exposed ECM and are activated, undergoing a shape change and granule release. Released ADP and thromboxane A2 (TXA2) induce additional platelet aggregation through platelet GpIIb-IIIa receptor binding to fibrinogen, and form the primary hemostatic plug. (C) Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, “cementing” the platelets into a definitive secondary hemostatic plug. (D) Counterregulatory mechanisms, mediated by tissue plasminogen activator (t-PA, a fibrinolytic product) and thrombomodulin, confine the hemostatic process to the site of injury.
It should be emphasized that endothelial cells are central regulators of hemostasis; the balance between the anti-thrombic and prothrombotic activities of endothelium determines whether thrombus formation, propagation, or dissolution occurs. Normal endothelial cells express a variety of anticoagulant factors that inhibit platelet aggregation and coagulation and promote fibrinolysis; after injury or activation, however, this balance shifts, and endothelial cells acquire numerous procoagulant activities (activation of platelets and clotting factor, described above, see also
Fig. 4.11 ). Besides trauma, endothelium can be activated by microbial pathogens, hemodynamic forces, and a number of pro-inflammatory mediators. We will return to the pro-coagulant and anti-coagulant roles of endothelium after a detailed discussion of the role of platelets and coagulation factors in hemostasis since endothelium modulates the functions of platelets and can trigger coagulation.
The following sections describe roles of platelets, coagulation factors and endothelium in hemostasis in greater detail, following the scheme illustrated in
Fig. 4.5