How the Body Stops the Bleeding
Several mechanisms in the body work to halt bleeding quickly in the case of a vascular injury. The process of stopping the bleeding is called hemostasis. First, the smooth muscle around damaged blood vessels will automatically constrict to restrict blood flow and limit blood loss. The platelet plug is then formed to slow blood loss. However, to stop the bleeding altogether, a clot must be formed.
Contact Activation (Intrinsic) Pathway
The activation of clotting in response to a small, localized cut is accomplished through a series of enzymatic modifications to proteins in the blood called clotting factors that are present and continually circulating in the plasma of the blood. When connective tissue materials are exposed to these plasma-clotting factors, an activation complex is organized.
The initiation of blood clotting relies on several factors, including prekallikrein and FXII (Hageman factor). When these factors bind to collagen, they convert prekallikrein to kallikrein, which activates FXII. This starts the cascade of activations with FXII activating FXI, which activates FIX. Once activated, FIX combines with FVIII, phospholipids, and calcium to form a molecular complex that activates FX, which is the first step in the common pathway for clotting.
Tissue Factor (Extrinsic) Pathway
Both initiation pathways (intrinsic and extrinsic) occur simultaneously. In the extrinsic pathway, when endothelial cells are damaged, FVII leaves the circulation and binds with TF (tissue factor), which forms an activation complex with phospholipids and calcium to activate FX and initiate the common clotting pathway.
Common Pathway
Whether activated through the intrinsic or extrinsic pathway, FX combines with FV, phospholipids, and calcium to form the prothrombinase complex. This complex converts the inactive plasma protein prothrombin into the active enzyme thrombin, which transforms fibrinogen into the active and sticky filamentous molecule fibrin. A web of fibrin begins to form and become the foundation of the blood clot as cells, platelets, molecules, and more fibrin coagulate in the site of the injury and stop the bleeding. Although the clot is now formed, it remains somewhat fragile, and the fibrin filaments must be cross-linked for stability by FXIII. It can take up to 45 minutes for the clot to fully stabilize.
Preventing clots
Removing calcium is one way to prevent blood from coagulating. Added to blood, the molecules EDTA (ethylenediaminetetraacetic acid) and citric acid inhibit clotting by binding calcium. Warfarin (Coumadin) was first identified from leeches, which use this substance to prevent blood clotting as the parasite feeds. It works by creating a vitamin K shortage at the cellular level and preventing the formation of a calcium-binding amino acid essential to clotting.
The clot does not persist forever. As the wound heals, the fibrin web retracts and assists in pulling the healthy tissue closer together. Eventually the clot is completely removed and the healing process is complete.