**6. Thrombosis**

Blood clotting occurs at the site of injury to prevent the leakage of the blood However in thrombosis, blood clots are formed in the blood vessel without any damage response and occlude the blood vessel [96]. Thrombosis is classified based on the location of the clot formation, it includes atrial thrombosis, venous thromboembolism (VTE) and pulmonary embolism (PE) [97, 98]. Thrombosis causes high mortality in United States where, annually 900,000 patients develop VTE and 300,000 people die due to PE [99–101]. Atrial emboli is found predominantly in surgical and intensive care patients due to preexisting conditions such as age, hypercoagulability, cardiac abnormalities and atherosclerosis [102]. Most often the clots are found in the veins due to low shear rates in veins (20–200/s) compared to arteries (300–800/s) [103]. Thrombosis found in veins is termed as venous thrombosis. The thrombus formation in the deep veins is termed as deep vein thrombosis. The risk factors for thrombosis are classified by Virchow and they referred as Virchow's Triad [104]. The triad includes endothelial injury, stasis or turbulence of blood flow, and blood hypercoagulability. Endothelial injuries generally happen during surgery, the turbulence of blood flow occurs due to cardiovascular disorders or hypertension [104]. Hypercoagulability is caused by the environment, unhealthy habits and age. The environmental risk factors include exposure to high altitudes and hypoxic environment [103]. The external risk factors for the thrombosis include smoking, chronic alcoholism and consumption of oral contraceptive pills [103]. Similarly, health conditions like cancer, obesity and aging promote the risk of thrombosis [103]. The molecular mechanisms under these risk factors are yet to be understood. Thrombosis is also caused by inherited factors such as mutations in the genes that encode for coagulation factors or anticoagulants.

#### **6.1. Procoagulants - thrombosis**

Serine proteases of coagulation cascade play a vital role in the progression of clot formation [3]. Mutations in the proteases convert them into hyper active forms and some of the mutations prevent their degradation and enhance thrombin generation. High levels of FVIII, FIX, FVII and TF are known to cause the thrombosis [105].
