Physiology of Hemostasis

As a result of injury to the blood vessel endothelium, three events take place simultaneously:

1. Vasoconstriction (vascular phase)

2. Platelet plug formation (primary hemostatic mechanism—platelet phase)

3. Fibrin thrombus formation (initiation, amplification, and propagation phases).

Relevant Components of Hemostasis

Endothelial cells secrete substances that repel platelets (prostaglandin I2 [PGI2], and nitric oxide), initiate coagulation (collagen, fibronectin), promote platelet adhesion (von Willebrand's factor [vWF]), platelet aggregation (adenosine diphosphate [ADP] and fibrin dissolution (tissue plasminogen activator), catalyze the inhibition of thrombin (heparin and thrombomodulin), and inhibit the initiation of fibrin dissolution (tissue plasminogen activator inhibitor).

Participation of platelets in hemostasis is a fundamental component of the physiologic process of coagulation. Platelet interactions in coagulation are initiated by adhesion to areas of vascular injury. Subsequent activation of platelets results in release of ADP, serotonin, and calcium from "dense bodies" and fibrinogen, vWF, factor V, HMW kininogen, fibronectin, ^-antitrypsin, P-thromboglobulin, platelet factor 4 (PF4), and platelet-derived growth factor from a-granules. Platelets provide surfaces for the assembly of coagulation factors (e.g.,VIIIa/Ca2+/IXa and Va/Ca2+/Xa complexes). The platelets aggregate and increase the mass of the hemostatic plug. They also mediate blood vessel constriction (by releasing serotonin) and neutralize heparin.

All of the plasma coagulation factors are produced in the liver; factor VIII is also produced by endothelial cells. Table 11-1 lists the half-life and plasma levels of the coagulation factors. Factors II, VII, IX, and X are vitamin K dependent and require vitamin K in order to undergo post-translational gamma carboxylation. These vitamin K-dependent factors circulate in zymogen form, are activated on platelet phos-pholipid surfaces, and upon activation have serine protease activity. The plasma coagulation factors work in an interdependent manner to generate thrombin (factor IIa) from prothrombin (factor II); thrombin then digests fibrinogen to form fibrin monomers. Fibrin monomers polymerize and establish a network. By incorporating

Table 11-1. Half-Life and Plasma Levels of Coagulation Factors

Was this article helpful?

0 0

Post a comment