BBS2001 Threats and Defenses - Cases and Consolidation Assignments - BBS2001 (BBS2001) - Stuvia US

3) Secondary haemostasis - Coagulation

The transformation from the platelet plug into the coagulation plaque occurs via two pathways, which eventually intertwine with each other, the so-called intrinsic and extrinsic pathway. The Intrinsic Pathway begins when collagen or other activators are exposed, which activates Factor XIIa, which then with the help of Ca2+ ions activates Factor XIa, which activates Factor IXa which then forms a complex with Factor VIII and activates Factor Xa. The Extrinsic Pathway activates due to exposed Tissue Factors (Factor III), which forms a complex with Factor XII and thereby also activates Factor Xa. Further down this cascade, in the Common Pathway, this pivotal Xa works together with Va and PL and Ca2+ to catalyse the prothrombin into active thrombin, and therefor creates the ‘thrombin burst’. This thrombin (Factor II) burst also signals platelets, but its main function is the enhancement from the deactivated Fibrinogen into the active Fibrin (Factor I). This fibrin mashes together with other fibrin molecules, under the influence of Factor XIII activated by thrombin itself and Ca2+ ions, which cross-links all fibres and holds together the components of the coagulation clot. , These three steps however only form a temporary fix, when the blood vessels slowly starts repairing itself plasminogen activates into plasmin, under the influence of thrombin and tissue Plasminogen Activator (tPA), which then slowly disintegrates the clot by destabilizing fibrin (so-called fibrinolysis). If it were not for chemical differences/barriers between damaged vessels and undamaged endothelial cells the blood vessels would clot altogether; the endothelial cells themselves in healthy circumstances prevent the platelets from adhering to the underlaying collagen. However also during the repair of damaged parts of blood vessels the endothelial cells are actively preventing the blood clot from becoming oversized, anticoagulants disrupt the intrinsic and extrinsic pathway in further proximity of the damage by interfering with certain factors; Heparin and Antithrombin III for example block off activated IX, X, XI and XII; Protein C inhibits V and VIII. The blood clotting thus is prevented, in healthy circumstances, as long as there is no tissue damage to the endothelial lining of the blood vessels. This prevention of blood clotting highly decreases the chance on thromboses, which can cause blood vessels to block off or even more dangerously cause the blood clot to shoot loose and enter the heart. However blood clotting as read so far is necessary to repair damaged blood vessels, thus coagulation cannot be prevented in all cases, but can be dissolved/ broken apart. This prevention is not only caused while no tissue factors can be bound, but also actively by Antithrombin III and prostacyclin, which block platelet aggregation and render coagulation factors inactive. When the blood vessel has been repaired, whilst the blood clot itself is only a temporary fix and not a permanent reparation, the endothelial cells (at least I would guess so) start synthesizing and releasing the nitric oxide and prostacyclin themselves again, and Tissue Plasminogen Activators. This beautiful tPA together with thrombin turns on plasminogen, and thus creates the active plasmin; this active plasmin breaks down the fibrin threads and cross links and therefor destabilizes the blood clot, causing it to dissolve; fibrinolysis. DAMPS