Overview
From Vascular Injury to a Stable Clot
The cell based model of coagulation has replaced the traditional cascade model.
The cell-based model of coagulation has replaced the traditional cascade model. Initiation occurs on tissue factor-bearing cells where TF-VIIa generates small amounts of thrombin. Amplification occurs on activated platelet surfaces where thrombin activates factors V, VIII, XI, and platelets. Propagation involves tenase (IXa-VIIIa) and prothrombinase (Xa-Va) complexes on platelet surfaces generating a thrombin burst sufficient for stable fibrin clot formation. Natural anticoagulants include antithrombin III (heparin cofactor; inhibits IIa, Xa, IXa), protein C pathway (thrombomodulin-thrombin activates protein C, which with protein S inactivates Va/VIIIa), and TFPI (limits TF-VIIa). Fibrinolysis: plasminogen is converted to plasmin by tPA, degrading fibrin into D-dimers and fibrin degradation products. This model explains why a clot is localized rather than a body-wide event. Tissue factor starts coagulation where vascular disruption exposes it; platelets then provide the negatively charged surface on which enzyme complexes assemble. Thrombin is the pivotal amplifier: it activates platelets and cofactors, converts fibrinogen to fibrin, and stabilizes the developing plug through factor XIII. Anticoagulant pathways and fibrinolysis restrain the reaction once the injury is controlled. The traditional pathway labels remain clinically useful because...
