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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Understand the significance of hemostasis and thrombosis in health and disease.

  • Outline the pathways of coagulation that result in the formation of fibrin.

  • Identify the vitamin K–dependent coagulation factors.

  • Provide examples of genetic disorders that lead to bleeding.

  • Describe the process of fibrinolysis.

  • Outline the steps leading to platelet aggregation.

  • Identify antiplatelet drugs and their mode of inhibition of platelet aggregation.

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BIOMEDICAL IMPORTANCE

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Basic aspects of the proteins of the blood coagulation system and of fibrinolysis are described in this chapter. Some fundamental aspects of platelet biology are also presented. Hemorrhagic and thrombotic states can cause serious medical emergencies, and thromboses in the coronary and cerebral arteries are major causes of death in many parts of the world. Rational management of these conditions requires a clear understanding of the bases of blood coagulation, fibrinolysis, and platelet activation.

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HEMOSTASIS & THROMBOSIS HAVE THREE COMMON PHASES

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Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupture of an atherosclerotic plaque). These processes involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates and fibrin.

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In hemostasis, there is initial vasoconstriction of the injured vessel, causing diminished blood flow distal to the injury. Then, hemostasis and thrombosis share three phases:

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  1. Formation of a loose and temporary platelet aggregate at the site of injury. Platelets bind to collagen at the site of vessel wall injury, form thromboxane A2, and release ADP, which activate other platelets flowing by the vicinity of the injury. (The mechanism of platelet activation is described below.) Thrombin, formed during coagulation at the same site, causes further platelet activation. Upon activation, platelets change shape and, in the presence of fibrinogen and/or von Willebrand factor, aggregate to form the hemostatic plug (in hemostasis) or thrombus (in thrombosis).

  2. Formation of a fibrin mesh that binds to the platelet aggregate, forming a more stable hemostatic plug or thrombus.

  3. Partial or complete dissolution of the hemostatic plug or thrombus by plasmin.

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There Are Three Types of Thrombi

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Three types of thrombi or clots are distinguished. All three contain fibrin in various proportions.

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  1. The white thrombus is composed of platelets and fibrin and is relatively poor in erythrocytes. It forms at the site of an injury or abnormal vessel wall, particularly in areas where blood flow is rapid (arteries).

  2. The red thrombus consists primarily of red cells and fibrin. It morphologically resembles the clot formed in a test tube and may form in vivo in areas of retarded blood flow or stasis (eg, veins) with or without vascular injury, or it may form at a site of injury or in an abnormal ...

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