Homeostasis is a well regulated process that maintains in a fluid, clot-free state in normal vessels and induces the rapid formation of a localized hemostatic plug at the site of vascular injury. In this dynamic process, blood coagulation is initiated and terminated in a rapid and tightly regulated fashion, which can be viewed as occurring in three phases; primary haemostatic, coagulation cascade, and fibrinolytic system.
Vascular endothelium and platelets are the two main players in primary homeostasis. Vascular endothelium is located strategically at interface between tissue and blood. It is pivotal for protecting against vascular injury and maintaining blood fluidity. Injury to the endothelium is accompanied by expression of adhesive molecules and increased procoagulant the balance of homeostasis’ via prothrombotic effects and anti-thrombotic properties.
Primary homeostasis is triggered in response to the damage of the vascular wall and the exposure of blood to sub-endothelial tissue. Several coordinated interactions among tissue components, plasma proteins and receptors on platelets lead to initial sealing of the damaged vessel wall. The formation of the primary platelet plug is temporally and spatially coordinated with the activation of the blood coagulation system.
Coagulation cascade
The coagulation factors are generated in liver cells, except for the von Willebrand factor, which is produced in multiple organs, the endothelial cells and megakaryocytes. They circulate in the plasma as pro-enzymes and pro-cofactors, and when activated supply some of the components needed for clot formation.
The model of the coagulation represents an evolution of the initial models of coagulation based on the cascade or the waterfall hypothesis, which described each clotting factor as a pro-enzyme that could be converted to an active enzyme and suggested that the clotting sequences were divided into two pathways. Coagulation could be initiated via an “intrinsic pathway”, so named because all the components were present in blood, or by an “extrinsic pathway”, in which the sub-endothelial cell membrane protein, tissue factor(TF), is required in addition to circulating components.
In the model of the coagulation cascade, the interaction of the proteins are outlined in a Y-shaped scheme, with distinct “intrinsic” and “extrinsic” pathways.
These Models give a good representation of the processes observed in clinical coagulation laboratory tests. The prothrombin time (PT) measures the factors of the so-called extrinsic and/or common pathway, and activated partial thromboplastin time (aPTT) measures factors in the intrinsic and /or common pathway.
Fibrinolytic system
The fibrinolytic system comprises plasminogen, an inactive proenzymes, that is converted by the plasminogen activators to the active enzyme, plasmin, which degrades fibrin.
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