In Situ Thrombosis 🩸
In situ thrombosis is the formation of a clot directly at the site of vascular injury.
It reflects a coordinated interaction between the vessel wall, platelets, and the coagulation cascade — classically described by Virchow’s triad (endothelial injury, abnormal blood flow, hypercoagulability).
Physiologically, this process prevents haemorrhage; pathologically, it underpins myocardial infarction, ischaemic stroke, and peripheral arterial occlusion.
⚡ Endothelial Injury
Healthy endothelium is actively antithrombotic — producing nitric oxide (NO), prostacyclin (PGI₂), and expressing thrombomodulin.
When damaged, this protective barrier is lost and subendothelial pro-thrombotic structures are exposed.
- Common Causes:
- 🧱 Atherosclerotic plaque rupture
- 🔪 Mechanical injury (trauma, surgery, PCI)
- 🔥 Vasculitis or inflammatory endothelial damage
- 🦠 Endothelial dysfunction (diabetes, smoking, hypertension)
- Consequence:
Exposure of subendothelial collagen, von Willebrand factor (vWF), and tissue factor (TF) to circulating blood — triggering platelet adhesion and coagulation activation.
🧲 Platelet Adhesion
- Initial tethering: Platelets bind to exposed collagen via vWF acting as a bridge to the platelet GpIb receptor.
- Adhesion becomes firm: Additional collagen receptors (GpVI, integrins) stabilise attachment.
- Platelet activation: Platelets undergo shape change (discoid → spiky), increasing surface area and procoagulant activity.
- 📦 Dense granules release ADP, calcium, and serotonin.
- 🧪 Alpha granules release fibrinogen and vWF.
🔗 Platelet Aggregation
- ADP and thromboxane A₂ (TXA₂) amplify recruitment of additional platelets.
- Activated platelets express GpIIb/IIIa receptors.
- 🪢 Fibrinogen bridges GpIIb/IIIa receptors between platelets → forming the primary platelet plug.
- 🌀 TXA₂ also promotes vasoconstriction, reducing local blood flow and limiting blood loss.
🧬 Coagulation Cascade Activation
- Tissue Factor (TF) exposure activates the extrinsic pathway (TF + Factor VIIa).
- The intrinsic pathway (Factors XII, XI, IX, VIII) amplifies thrombin generation.
- Both converge at the common pathway → activation of Factor X → conversion of prothrombin to thrombin (Factor IIa).
- 🔥 Thrombin is the key enzyme:
- Converts fibrinogen → fibrin
- Activates Factors V, VIII, XI (positive feedback)
- Further activates platelets
🕸️ Formation of a Stable Thrombus
- Thrombin converts soluble fibrinogen into insoluble fibrin strands.
- Factor XIII cross-links fibrin → strengthening the clot.
- The fibrin mesh stabilises the platelet plug → forming a stable thrombus.
- In arteries, these clots are platelet-rich (“white thrombi”); in veins, fibrin-rich (“red thrombi”).
⚖️ Regulation and Dissolution (Fibrinolysis)
- Clot formation is tightly regulated by endogenous anticoagulants:
- 🛡️ Antithrombin (inhibits thrombin, Xa)
- 🧪 Protein C & Protein S (inactivate Va and VIIIa)
- 🌿 Tissue factor pathway inhibitor (TFPI)
- Once healing begins, fibrinolysis restores patency.
- Tissue plasminogen activator (tPA) converts plasminogen → plasmin.
- 🧹 Plasmin degrades fibrin → producing fibrin degradation products (including D-dimer).
- Clinical note: Imbalance between pro-thrombotic and anti-thrombotic forces results in pathological thrombosis — leading to ischaemia, infarction, or embolic complications.
