Thrombosis. Pathogenesis, thrombus morphology, types. Outcome of thrombosis
Thrombosis is the formation of a blood clot (primarily platelets and fibrin) inside a blood vessel, which obstructs the flow of the blood through the circulatory system.
Pathogenesis
The pathogenesis of thrombosis is summed up by Virchow's triad. He described three factors that contribute to thrombosis:
- Hypercoagulability
- Hemodynamic changes (stasis and turbulence)
- Endothelial injury
Lets address the etiology of each in turn.
Hypercoagulability can be caused by genetic defects or autoimmune disorders.
Examples: inherited – factor V Leiden (the commonest), prothrombin gene mutation, antithrombin, protein C or S deficiency; acquired – prolonged immobilisation, surgery, pregnancy, oral contraceptives, disseminated cancer (Trousseau syndrome), antiphospholipid syndrome, heparin-induced thrombocytopenia.
Hemodynamic changes can be the result of:
- Blood stagnation, possible causes include:
- Long periods of sedentary behaviour
- Heart failure
- Atrial fibrillation
- Cancers/malignancies
- Formation of intravascular plaques
Endothelial injury can be the result of hypercholesterolemia, hypertension, smoking, radiation, chemical irritation and others.
Thrombus morphology
Thrombi have a rough surface, due to more fibrin deposition, and are red or pale tan based on the number of erythrocytes. Thrombi are attached to the vascular wall, this is in contrast to post-mortem clots which are unattached.
H&E, recent thromboembolus: lines of Zahn – pale layers of platelets and fibrin alternating with dark red layers of red cells.
Image: “Pulmonary thromboembolus, recent (3626658803)” by Yale Rosen from USA, CC BY-SA 2.0, via Wikimedia Commons.
Remember: thrombi formed in flowing blood show lines of Zahn – alternating pale layers of platelets and fibrin and dark layers of red cells – proof that they formed during life. Postmortem clots are rubbery, unattached, with a dark red 'currant jelly' lower part and a yellow 'chicken fat' upper part.
Thrombi are made up of aggregated platelets and red blood cells, forming the plug, as well as the cross-linked fibrin protein.