Thrombosis : Definition, Pathogenesis, Morphology & Fate (HD)

Summary

In this educational video, Dr. Robul, a pathology lecturer, explains thrombosis, detailing its definition, pathogenesis, and morphology. He explores Virchow’s Triad—endothelial injury, altered blood flow, and hypercoagulability—and their interconnected roles in thrombus formation. The video covers arterial and venous thrombi, highlighting their differences, common sites, and compositions, and explains the characteristic lines of Zahn seen in thrombi. Dr. Robul also discusses the four possible fates of thrombi—propagation, embolization, dissolution, and organization with recanalization—and concludes with a clear comparison between antemortem thrombi and postmortem clots, making complex concepts accessible for students and viewers alike.

Takeaways

• 🩸 Thrombosis is the formation of a solid mass (thrombus) in an uninterrupted cardiovascular system from flowing blood constituents.
• 🧬 Virchow’s Triad explains thrombosis pathogenesis: endothelial injury, alteration of blood flow, and hypercoagulability.
• 🏥 Endothelial injury promotes thrombosis by losing anti-thrombotic properties and exposing subendothelial tissue; causes include atherosclerotic plaque rupture, vasculitis, diabetes, and toxins.
• 💨 Alteration of blood flow, including turbulence and stasis, disrupts laminar flow, bringing platelets in contact with endothelium and promoting thrombus formation.
• ⚖️ Hypercoagulability (thrombophilia) can be primary (genetic, e.g., Factor V mutation) or secondary (acquired, e.g., immobilization, myocardial infarction).
• 🔬 Thrombi exhibit Lines of Zahn: alternating pale (platelet/fibrin) and dark (RBC-rich) layers, reflecting their formation in flowing blood.
• 🫀 Arterial thrombi are platelet-rich, grow retrograde, and commonly occur in coronary, cerebral, and femoral arteries; venous thrombi are RBC-rich, grow with blood flow, and often occur in lower limb veins.
• ⏳ The fate of a thrombus includes propagation, embolization, dissolution, and organization/recanalization, sometimes occurring in combination.
• ⚡ Postmortem clots differ from antemortem thrombi: they are gelatinous, loosely attached, take vessel shape, and lack Lines of Zahn.
• 🧪 Anti-thrombotic substances released by endothelium include heparin-like molecules, thrombomodulin, platelet aggregation inhibitors, and tissue plasminogen activator, all crucial for preventing thrombosis.

Q & A

What is thrombosis and how is a thrombus defined?

Thrombosis is the process of formation of a solid mass within an uninterrupted cardiovascular system or circulation from the constituents of flowing blood. The solid mass itself is called a thrombus.

What are the three components of Virchow's Triad that contribute to thrombosis?

The three components of Virchow's Triad are endothelial injury, alteration of blood flow, and hypercoagulability. Each of these factors can independently or interactively contribute to thrombus formation.

How does endothelial injury lead to thrombosis?

Endothelial injury leads to thrombosis by exposing subendothelial tissue, which is thrombogenic, and by reducing the anti-thrombotic properties of endothelial cells, such as secretion of heparin-like substances, thrombomodulin, inhibitors of platelet aggregation, and tissue plasminogen activator.

What are some common causes of endothelial injury in arteries and the heart?

In the heart, causes include endocardial damage from myocardial infection, myocarditis, or cardiac surgery. In arteries, causes include rupture or ulceration of atherosclerotic plaques, vasculitis, diabetes, hypertension, metabolic disturbances like hypercholesterolemia, and exogenous toxins like cigarette smoke.

Explain the difference between laminar flow and turbulent or stasis conditions in blood flow.

Laminar flow is the normal, orderly flow of blood, with red and white blood cells in the center, platelets surrounding them, and plasma at the outer layer. Turbulence refers to irregular or unequal blood flow, while stasis refers to slowed or stagnant blood flow. Both conditions can disrupt laminar flow and increase the risk of thrombus formation.

What is hypercoagulability and what are its types?

Hypercoagulability, also known as thrombophilia, is a condition where the coagulation pathway is altered, predisposing to thrombus formation. It can be primary (genetic causes like Factor V Leiden mutation or deficiencies of anticoagulants) or secondary (acquired causes such as prolonged immobilization, myocardial infarction, atrial fibrillation, or disseminated intravascular coagulation).

What are the lines of Zahn and why do they appear in thrombi?

Lines of Zahn are alternating pale and dark laminations seen in thrombi, especially mixed thrombi. Pale regions consist of platelets and fibrin, while darker regions contain red blood cells. These laminations occur due to the layering of different blood components during thrombus formation.

How do arterial and venous thrombi differ in composition and common locations?

Arterial thrombi contain platelets, fibrin, red blood cells, and degenerated white blood cells, commonly forming at sites of atherosclerotic plaque rupture, coronary arteries, cerebral arteries, or femoral arteries. Venous thrombi are rich in red blood cells due to slower circulation, usually forming in the lower limb veins, upper limb veins, ovarian veins, or special sites like dural sinuses or portal veins.

What are the four possible fates of a thrombus?

The four fates of a thrombus are: propagation (growth by further deposition of platelets and fibrin), embolization (detachment and travel to a distant site), dissolution (breakdown by fibrinolytic activity, mainly in recent thrombi), and organization with recanalization (ingrowth of endothelial cells, fibroblasts, and capillaries to restore some blood flow).

How can a thrombus be distinguished from a postmortem clot?

Antemortem thrombi are granular, firmly attached to the vessel wall, may or may not take the vessel shape, and display lines of Zahn. Postmortem clots are gelatinous, loosely attached, take the shape of the vessel, and show a yellow 'chicken fat' layer above a red gelatinous layer under the microscope.

Why is turbulence particularly important in arterial thrombosis, while stasis is more critical in venous thrombosis?

Turbulence in arteries can cause endothelial injury, local stasis pockets, and countercurrents that favor thrombus formation, especially under high flow conditions. In veins, where blood flow is naturally slower, stasis allows red blood cells to accumulate and increases the risk of venous thrombus formation.

What anti-thrombotic substances are secreted by intact endothelial cells, and how do they function?

Endothelial cells secrete heparin-like substances (enhances antithrombin III and inhibits clotting factors), thrombomodulin (activates protein C, an anticoagulant), inhibitors of platelet aggregation (like prostacyclin and adenosine diphosphate inhibitors), and tissue plasminogen activator (promotes fibrinolysis). These collectively prevent spontaneous thrombosis.