*6.1.3. Tissue factor and thrombosis*

Tissue factor is also known as Factor III (FIII), it is a 47 kDa glycoprotein highly expressed in the pericytes and adventitial fibroblasts, low levels of TF expression are observed in CD14-positive monocytes [113]. TF is expressed in the parenchyma of highly vascularized organs such as placenta, brain, heart, kidneys, and lungs [114]. Circulatory TF is found in macrovesicles produced by apoptotic bodies, smooth muscle cells, monocytes and cancer cells. TF expression is enhanced by pathological conditions such as bacterial infections and cancer [115, 116].

#### *6.1.4. Other procoagulants and thrombosis*

FXI levels more than 110 IU/dl increases the chances of thrombosis by 2 fold and inhibition of FXI in thrombosis models rescues the DVT. Prothrombin levels more than 115 IU/dl increases the risk of thrombosis by 2.1 fold. Plasma thrombin levels are reported to increase due to polymorphic variations. FV leiden is one the well-known FV variant that causes high risk of thrombosis. Koster et al. reported increase in fibrinogen levels increases the risk of thrombosis by 2.8 fold [105].

*6.2.3. Protein S*

PS is a vitamin K dependent single chain polypeptide consist of one Gla domain, four EGF like domains and two Laminin G domains. PS is primarily synthesized in liver and it circulates in the plasma at a concentration of 450 nM. 60% of circulatory PS is bound to compliment component binding protein 4b (C4BP) and only 40% of the circulatory PS is free [6, 120]. PS acts as a cofactor for APC and TFPI in inhibiting FVIIIa, FVa, and TF-FVIIa-FXa complex [121, 122]. PS was reported to directly interact with procoagulants such as FV, FIXa and FX and inhibit their function [121, 122]. PS plays a key role in regulating inflammation and clearing the apoptotic bodies from the system. PS deficiency enhances the risk of thrombosis and PS deficiency is classified as hereditary PS deficiency and acquired PS deficiency. Hereditary PS is caused by mutations in the PS gene and till date ~200 mutations are reported in PS gene. Acquired PS deficiency is caused by several factors such as, usage of oral contraceptive pills,

Understanding the Clotting Cascade, Regulators, and Clinical Modulators of Coagulation

http://dx.doi.org/10.5772/intechopen.75141

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Protein Z is a 62 kDa vitamin K dependent plasma protein that acts as a cofactor for 72 kDa serpin family protease inhibitor – Protein Z Dependent Protease Inhibitor (ZPI). ZPI-PZ com-

Thrombosis is treated by selectively inhibiting the major procoagulant proteins. Major drug targets for the treatment of thrombosis include vitamin K agonists, FXa, FIXa, Thrombin and platelet inhibitors. Current oral anticoagulants approved by FDA are rivaroxaban, Apixaban, dabigatran and endoxaban. Revaroxaban and Apixaban inhibit FXa, whereas dabigatran and endoxaban inhibit thrombin. Several other procoagulant inhibitors such as RNA aptamers are

An individual can acquire coagulation disorders due to several reasons. Infections such as streptococci cause thrombosis by inactivating Protein S [124]. Chronic smoking and chronic alcoholism effect coagulation system by altering the liver functions. Environmental factors like hypoxia, drugs like aspirin, oral contraceptive pills, dietary problems like vitamin K defi-

DIC is characterized by activation of clotting system within the vasculature which blocks the micro vessels and can cause further organ dysfunction [125]. In contrast, it can also accelerate fibrinolysis and cause severe bleeding. The international Society of Hematology (ISTH) has

pregnancy, consumption of vitamin K antagonists and pathogen infections.

*6.2.4. Protein Z and protein Z dependent protease inhibitor*

*6.2.5. Anticoagulants in the treatment for thrombosis*

**7. Acquired coagulation disorders**

ciency affect the blood coagulation [12, 56–61].

**7.1. Disseminated intravascular coagulation (DIC)**

plex rapidly inhibits FXa and FXIa [8].

under investigation [123].
