Thrombosis

Thrombosis (from ancient Greek θρόμβος, meaning “clot”) is a pathological process characterized by the formation of solid blood clots (thrombi) within the vessels or heart chambers during life. These blood clots impede normal blood flow. Thrombosis should be distinguished from postmortem coagulation and from the physiological hemostasis, in which clot formation serves to stop bleeding from a damaged vessel.

It underlies many common and life-threatening cardiovascular conditions, such as myocardial infarction, ischemic stroke and pulmonary embolism.

Etiology and Pathophysiology (Virchow’s Triad)

Pathogenesis of thrombosis is classically described by Virchow’s triad, which outlines three key factors contributing to blood clot formation. The presence of even one of these factors significantly increases the risk of thrombosis.

Components of Virchow’s triad:

1. Vascular wall damage (endothelial dysfunction):
   • Causes: Direct trauma, surgery, atherosclerosis (plaque rupture), inflammation (vasculitis), hypertension.
   • Mechanism: Disruption of the inner vascular layer (endothelium) exposes subendothelial components (collagen) activating the coagulation cascade and platelet adhesion.
2. Abnormal blood flow (hemodynamic changes):
   • Causes: Venous stasis due to immobility (bed rest, long flights), heart failure, atrial fibrillation. Turbulent (vortex) blood flow in areas of vessel narrowing or aneurysms.
   • Stasis promotes concentration of clotting factors and contact of platelets with the vessel wall. Turbulence may contribute to endothelial damage.
3. Hypercoagulability (increased blood clotting):
   • Causes: It may be congenital (e.g., Factor V Leiden mutation) or acquired (in cancer, pregnancy, oral contraceptive use, sepsis, dehydration).
   • Mechanism: Imbalance between the coagulation and anticoagulation systems, leading to excessive fibrin formation.

Clinical Significance and Types

The consequences of thrombosis depend on its type (arterial or venous) and location.

• Venous thrombosis: Most commonly presents as deep vein thrombosis (DVT) in the lower extremities. It manifests in leg swelling, pain and erythema. The major complication is pulmonary embolism (PE), which occurs when part of the blood clot (embolus) detaches and travels to the pulmonary arteries. It is a life-threatening condition.
• Arterial thrombosis: Usually develops at the site of an atherosclerotic plaque. It leads to acute ischemia (oxygen deficit) in the tissues supplied by the affected artery.
  • In the coronary arteries, it causes myocardial infarction.
  • In the cerebral arteries, it causes ischemic stroke.
  • In the arteries of the extremities, it causes acute limb ischemia.

Management of thrombosis focuses on preventing blood clot propagation and restoring blood flow. The most commonly used drugs include anticoagulants (heparin, warfarin), antiplatelet agents (aspirin, clopidogrel), and thrombolytics (clot-busting drugs). In some cases, surgical thrombectomy may be indicated.

Differential Diagnosis

The clinical presentation of thrombosis is often nonspecific, requiring precise diagnostic imaging to confirm the diagnosis. For example, leg swelling and pain in DVT must be differentiated from phlegmon, Baker cyst rupture, or muscle trauma. Chest pain in PE can mimic myocardial infarction or aortic dissection. The diagnosis is confirmed by imaging: compression ultrasonography is the standard for diagnosing DVT, and computed tomography with angiography is the standard for diagnosing PE and arterial thrombosis.