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LEARNING OBJECTIVES

LEARNING OBJECTIVES

  1. Conceptualize that coagulation is a complex but efficient process that culminates in the development of a fibrin clot and subsequent lysis of the clot ensures that the fluidity of blood is maintained.

  2. Recognize that the hemostatic system is a dynamic, evolving system in the fetal/neonatal stage that eventually matures into the adult version by the late teenage years.

  3. Identify the general principles, including specimen requirements for hemostasis and platelet testing.

  4. Identify the general principles, including specimen requirements for thrombophilia and assays related to anticoagulant testing.

  5. Recognize various tests of global hemostasis.

OVERVIEW OF THE BASIC COAGULATION AND FIBRINOLYSIS

Coagulation is the process that leads to fibrin formation and involves controlled interactions between protein coagulation factors. Hemostasis is coagulation that occurs in a physiological setting and results in sealing of a break in the vasculature by not only forming a fibrin clot but also by subsequent lysis of the clot to ensure that the fluidity of blood is maintained. The components involved in hemostasis consist of vessel walls, platelets, coagulation factors, inhibitors of coagulation, and the fibrinolytic system.

The enzymatic reactions leading to thrombin generation and an eventual fibrin clot were originally described as the waterfall1 or enzyme2 cascade, a model that remains conceptually useful today and is able to tie biology with diagnostic laboratory testing. Further insights on the evolution of this process have occurred over the past many decades as proteins have been purified, their function characterized, and additional factors identified. Human coagulation is now known to occur in vivo in the context of a cell-based model of coagulation (Figure 16-1). The cell-based model of hemostasis views the process as having three overlapping phases: initiation, amplification, and propagation, in which a break in the vasculature exposes extracellular matrix to blood and initiates the coagulation process. Tissue factor (TF) and factor (F) VIIa are considered the major initiators of coagulation, as opposed to the contact pathway which is now thought to be a key link between coagulation and inflammation. Tissue factor is expressed on vascular smooth muscle cells and on the pericytes that surround blood vessels, the so-called hemostatic envelope. Tissue factor is released upon cell damage or is secreted by cells, such as platelets and monocytes and activates FX, leading to the generation of a small amount of thrombin in the initiation phase of coagulation. Thrombin formed after the initiation phase can promote local fibrin formation, however, it is not sufficient to provide hemostasis throughout the wound area. This minute amount of thrombin then acts as an amplifier by activating platelets to facilitate platelet-driven thrombin generation. In addition to platelet processes, plasma concentrations of factors IX and VIII are brought to the preformed FVIIa/TF complexes at the site of injury. The FIXa/VIIIa complex activates factor X on the platelet surface. The platelet surface-generated FXa can move directly into a complex with platelet surface FVa ...

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