trombogenese

Thrombogenesis is the process by which a blood clot (thrombus) forms within a blood vessel. It is essential to stopping bleeding after injury but can contribute to pathological thrombosis when regulation fails. The process involves vascular injury, platelet activation, and coagulation factor activation, culminating in fibrin clot formation and thrombus stabilization.

Initiation: Endothelial damage or dysfunction exposes tissue factor and subendothelial components. Platelets adhere via von Willebrand factor and become activated, releasing ADP and thromboxane A2, recruiting more platelets, and starting small amounts of thrombin generation via the tissue factor pathway.

Propagation: On activated platelets, the coagulation cascade amplifies. The extrinsic pathway initiation TF-FVIIa complexes generate FXa and small thrombin; the intrinsic pathway amplifies it on platelet surfaces, generating large thrombin bursts. Thrombin converts fibrinogen to fibrin, stabilizing the clot.

Resolution and regulation: Fibrinolysis dissolves the clot; plasminogen is activated to plasmin by tissue plasminogen activator (t-PA). Anticoagulant pathways counterbalance coagulation (antithrombin, protein C and S, tissue factor pathway inhibitor), maintaining hemostasis.

Clinical relevance: Physiological thrombogenesis prevents hemorrhage, but pathological thrombosis can cause DVT, pulmonary embolism, myocardial infarction, or stroke. Risk factors follow Virchow's triad: endothelial injury, abnormal blood flow, and hypercoagulability. Therapies include antiplatelet drugs (aspirin, P2Y12 inhibitors) to limit platelet activation and anticoagulants (heparins, direct oral anticoagulants, vitamin K antagonists) to inhibit coagulation.