Hemostasis is defined as the process of clot formation. It is divided into four stages. The first stage involves the creation of a platelet plug consequent from disruption of the vascular endothelium from injuries due to diabetes, hypertension, smoking as well as vascular wall tear. Following damage to the vascular wall, Von Willibrand factor (VWF) is released by the endothelial cells and megakaryocytes, which mediates platelet adhesion to the damaged vascular surface, and aggregation of platelets.
The second stage involves the propagation of clots by activation of various proenzymes to their active form. This clotting cascade is a regulatory process of the clotting system initiated by the extrinsic pathway and propagated via the intrinsic pathway. The extrinsic pathway is initiated by factor III (tissue factor), a membrane-bound glycoprotein that is present in the subendothelial tissues and fibroblast. Tissue factor is activated by exposure from vascular disruption or damage. Exposed tissue factor binds to factor VII and calcium, which then converts factor X to activated factor X.
The intrinsic pathway results from activation of factor XI by factor XII, HMW Kininogen, and prekallikrein. Activated XI then activates factor IX. Activated factor IX in conjunction with its cofactor (factor VIII), leads to the activation of factor X.
The coagulation cascade has a common pathway that bridges the intrinsic and extrinsic pathways. Activated factor X with its cofactor (factor V) in conjunction with calcium, tissue and platelet phospholipids, converts prothrombin to thrombin. Thrombin breaks circulating fibrinogen to fibrin and activates factor XIII, which crosslinks fibrin leading to a stable clot.
The third stage in the clotting process is the termination of clot formation and the antithrombin control mechanism which are designed to prevent and mediate the extent of clot formation, thereby preventing processes that can lead to thrombosis, vascular inflammation, and tissue damage. This phase in the clotting pathway ensures the fluidity of blood.
Removal of the clot by fibrinolysis is the last stage in clot formation. This stage ensures the removal of organized clot by plasmin as well as wound healing and tissue remodeling.
Anticoagulation or clot prevention can be directed at different sites of the coagulation pathway, with overlaps at multiple points. Direct thrombin inhibitors and direct factor Xa inhibitors can inhibit the formation of a fibrin clot. Other mechanisms through which anticoagulation can be achieved include inhibition of vitamin K-dependent factors by preventing their synthesis in the liver or modification of their calcium-binding properties.
The use of anticoagulation in pregnancy is an important consideration; pregnancy is associated with a five-fold increase in the risk of venous thromboembolism, with the risk rising to twenty-fold or more during puerperium. The risk further increases if underlying thrombophilia is present. The risk of venous thromboembolism persists until nearly 12 weeks postpartum.