Coagulation
Overview
Coagulation, also known as clotting, is a complex process by which the blood forms clots. It is an essential part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered by a platelet and fibrin clot to stop the bleeding and begin repair of the damaged vessel. Abnormalities or disease conditions involving coagulation can lead to an increased risk of bleeding (hemorrhage) or obstructive clotting (thrombosis).
Coagulation Process
Coagulation involves a cellular (platelet) and a protein (coagulation factor) component. When the integrity of the blood vessel wall is compromised, platelets immediately adhere to the sub-endothelium surface within seconds of a breach in vessel integrity. This process is mediated by the platelet receptor GPIb and the von Willebrand factor (vWF) which is present in the sub-endothelium. This adhesion is strengthened further by the binding of integrin αIIbβ3 on the platelet membrane to fibrinogen, which links adjacent platelets together.
Coagulation Factors
The coagulation factors are proteins that are essential for blood clotting. They are produced by the liver and by blood platelets. The factors are numbered using Roman numerals (I through XIII) in the order of their discovery. Deficiencies in these factors can lead to bleeding disorders such as hemophilia and von Willebrand disease.
Coagulation Cascade
The coagulation cascade is a series of reactions, which is classically divided into three pathways. The intrinsic pathway (also known as the contact activation pathway), the extrinsic pathway (also known as the tissue factor pathway), and the common pathway. Each pathway is a cascade of biochemical reactions, in which a coagulation factor (protein) is activated and then cleaves and activates the next factor in the sequence. Ultimately, the series of reactions culminate in the production of a fibrin clot.
Regulation of Coagulation
Regulation of coagulation is a critical aspect of hemostasis. The body must maintain a delicate balance between clot formation and dissolution in order to repair tissue damage and prevent blood loss, while at the same time preventing the formation of clots that obstruct blood flow. This is achieved through several mechanisms, including anticoagulant proteins, fibrinolysis, and the protein C pathway.
Disorders of Coagulation
Disorders of coagulation can lead to an increased risk of bleeding (hemorrhage) or clotting (thrombosis). Hemorrhagic disorders are caused by a deficiency of clotting factors, while thrombotic disorders are typically caused by an overactivity of the coagulation system. Some common coagulation disorders include hemophilia, von Willebrand disease, and thrombophilia.