**2. Defects in hemostasis**

phosphatidylserine-rich membrane surface, this complex converts FX to FXa. Intrinsic/ contact pathway is initiated by artificial surfaces in the plasma. Artificial surfaces induce conformational change in factor XII (FXII) and results in activation of small amount of FXII. Activated factor XII (FXIIa) activates high molecular weight kininogen (HK) and plasma prekallikrein (PK) and this acts as a positive feedback loop for FXII activation [1–4]. Further, FXIIa activates Factor XI (FXI) to FXIa, which intern activates FIX. Both extrinsic and intrinsic pathways collaborate with a common pathway that involves activated FXa. FXa binds to activated factor V (FVa), forming prothrombinase complex and Prothrombinase complex cleaves prothrombin to generate activated thrombin. Thrombin cleaves fibrinogen to fibrin, these fibrin monomers

Along with the clotting factors, platelets play a vital role in regulating the hemostasis by forming a cellular plug at the site of injury. The circulating platelets get immobilized at the sub endothelial surface of the site of injury by binding to the von Willebrand factor (VWF) [3]. Platelet receptor GPIb-IXV is essential for this process. Similarly, receptor GPVI helps to anchor the platelets at the site of injury with the help of collagen. Further these platelets get activated and expose phosphatidylserine, which provides a lipid surface for the clotting factors [3]. Among the clotting factors, fibrin helps in activating the platelets by cleaving the

Hemostasis is tightly monitored by feedback mechanisms, where anticoagulants inhibit the protease function of coagulation favors by directly inhibiting them or their cofactors [1–4]. The natural anticoagulants include tissue factor pathway inhibitor (TFPI), Activated protein C (APC), Protein S (PS) and Protein Z (PZ). These anticoagulants help in regulating blood clot

**Figure 1.** (A) Schematic representation of coagulation cascade. (B) Schematic representation of platelet plug formation.

(C) TFPI pathway. (D) APC function. (E) PZI pathway. (F) Clot lysis.

protease activated receptors (PARs) that include PAR1 and PAR4 (**Figure 1B**).

polymerizes to form insoluble fibrin polymer (**Figure 1A**).

132 Hematology - Latest Research and Clinical Advances

Quantitative or qualitative defects in the coagulation factors lead to hemostatic defects such as hemophilia or thrombosis [10, 11]. Hemophilia is characterized by defects in clotting factors and it is characterized by spontaneous or periodic bleedings [11]. Whereas, thrombosis is caused by the high amount of procoagulants in the plasma, hyper activation of procoagulants or defects in anticoagulants [10]. Thrombosis is characterized by systemic clots which impair the normal hemostasis. Bleeding disorders are also classified hereditary and acquired disorders. Hereditary disorders are associated with gene mutations and inherited to the offspring [11]. The major hereditary disorders are hemophilia, rare bleeding disorders and thrombosis. Acquired disorders are caused by several factors such as infections, habits and environmental effects [12].
