**1. Introduction**

#### **1.1. Primary and secondary hemostasis**

Hemostasis is the human body's physiological response to blood vessel injury and subsequent prevention of hemorrhage [1–3]. This significant three-step biological process involves a concerted coordination between blood clotting proteins and platelets with the consequent formation of a clot (repair of a damaged vascular tissue) or thrombus (clot in a healthy blood vessel). According to the cell-based coagulation model (**Figure 1**), this process involves: primary and secondary hemostasis, and fibrinolysis [4].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

complex activates **Factor X to FXa**, and FXa combines with FVa to produce small amounts

FXa Direct Synthetic Inhibitors

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• *Amplification*: produces small amounts of thrombin activated platelets increasing platelet adhesion and promoting **FXa and cofactors to catalyze the production of more than 1000** 

• *Propagation*: the protein complexes are assembled on the platelet surface resulting in largescale thrombin generation. After that, fibrin production starts with the clot formation. Finally, stabilization contributes to the formation of a thrombus, thus producing the world-

Over the past few decades, the fact that cardiovascular syndromes are a leading cause of heart problems and rising death rates in the US and Europe has been gradually accepted. With more than 24,000 deaths annually, cerebrovascular accidents (CVA) represent almost a third

of thrombin, which subsequently activate platelets during the amplification phase.

**thrombin molecules from each FXa unit.**

wide pathology called thrombosis [5–7].

**Figure 2.** Thrombus production on blood vessels.

**1.2. Thrombosis**

of all deaths [8–12].

**Figure 1.** Cell-based coagulation model. Figure adapted from Vojacek [8].

*Primary hemostasis* causes local vasoconstriction which diminishes blood flow at the injury site and platelet plug formation. *Secondary hemostasis* implicates a series of enzymatic reactions between coagulation factors and cellular activity. These enzymatic reactions convert fibrinogen to fibrin, an insoluble strand, which together with platelets forms a thrombus.

Lastly, *fibrinolysis* is the biological mechanism which disperses the clot after the blood vessel has healed.

The cell-based model includes the interactions between cells, platelets, and coagulation factors. This model postulates a three-phase process:

• *Initiation*: occurs after vascular injury and leads to the production of a small amount of thrombin. Tissue factor (TF) localized to the cell membrane is activated by non-coagulation and coagulation proteases (blood clotting proteins or factors). The produced FVIIa/TF complex activates **Factor X to FXa**, and FXa combines with FVa to produce small amounts of thrombin, which subsequently activate platelets during the amplification phase.

