Coagulation Pathway

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  • Topic: Coagulation, Coagulation system, Factor X
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  • Published : May 8, 2013
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CHAPTER 1

Coagulation Pathway and Physiology
Jerry B. Lefkowitz, MD

Introduction
Our understanding of blood clotting is intimately tied to the history of civilization. With the advent of writing 5000 years ago, it could be argued that the first symbols used for blood, bleeding, or clotting represented the first published coagulation pathway. The ancient peoples of the world always held blood in utmost mystical esteem. Through the ages, this esteem has been transmitted to modern times in the many expressions that use “blood,” such as “blood is thicker than water,” “blood of our fathers,” and others. Mysticism aside, the study of blood clotting and the development of laboratory tests for blood clotting abnormalities are historically inseparable. The workhorse tests of the modern coagulation laboratory, the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), are the basis for the published extrinsic and intrinsic coagulation pathways, even though it is now known that these pathways do not accurately reflect the function of blood clotting in a living organism. In this chapter, and ultimately this textbook, the many authors hope to present a clear explanation of coagulation testing and its important place in the medical armamentarium for diagnosing and treating disease.

tic system occupies a site at the vertex of an equilateral triangle. This representation implies that each system constituent interacts with and influences all other constituents. In the normal resting state, these interactions conspire to maintain the fluidity of the blood to ensure survival of the organism. Normally, only at the site of an injury will the fluidity of the blood be altered and a blood clot form.

Endothelium
Figure 1-2 shows some of the basic properties of the endothelium. The endothelium normally promotes blood fluidity, unless there is an injury. With damage, the normal response is to promote coagulation at the wound site while containing the coagulation response and not allowing it to propagate beyond this site. Until recently, the dogma of blood clotting suggested that the single, major procoagulant function of the endothelium is to make and express tissue factor with injury. Endothelial cells do not normally make tissue factor but may synthesize it following cytokine stimulation or acquire the material from activated monocytes in the circulation. Tissue factor is a glycosylated intrinsic membrane protein that is expressed on the surface of Coagulation Proteins

Constituents of the Hemostatic System
With the evolution of vertebrates and their pressurized circulatory system, there had to arise some method to seal the system if injured—hence the hemostatic system. Interestingly, there is nothing quite comparable to the vertebrate hemostatic system in invertebrate species. In all vertebrates studied, the basic constituents of the hemostatic system appear to be conserved. Figure 1-1 illustrates the three major constituents of the hemostatic pathways and how they are interrelated. Each element of the hemosta-

Platelets

Endothelium

Figure 1-1. Basic representation of the elements of hemostasis.

3

I

HEMOSTASIS PHYSIOLOGY

Procoagulant
Thrombin activatable fibrinolytic inhibitor (TAFI) Plasminogen activator inhibitor (PAI-1) Tissue factor pathway inhibitor (TFPI)

Anticoagulant
Tissue plasminogen activator (tPA) Protein C Activated protein C (APC)

Activated TAFI

Thrombin / thrombomodulin Expression of tissue factor ?? von Willebrand factor Prostacyclin (PGI2)

Thrombin / thrombomodulin

Heparin-like material Thrombin Thrombomodulin receptor

Endothelial lining of vessel Subendothelial matrix Figure 1-2. A stylized view of endothelial functions related to procoagulation and anticoagulation. The subendothelial matrix, represented by the purple interlocking lines, is a complex of many materials. The most important constituents of the subendothelial matrix related to...
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