Lecture 5.1 - Thrombosis and Embolism

Thrombosis

• Defined as a solidification of blood contents that forms within the vascular system, resulting in a solid mass in the lumen of the vessels (occluded lumen)

Virchow's Triad

• Formed by three factors, with only two necessary to form a thrombus:
  • Changes in the intimal surface of the vessel
  • Changes in the pattern of blood flow (sluggish, turbulent blood flow, etc.)
  • Changes in the blood constituents (e.g., pregnancy, surgery, smokers, inherited thrombophilias)

Endothelial Damage

• Occurs in situations including:
  • After myocardial infarction
  • Secondary to haemodynamic stress of hypertension
  • On scarred heart valves
  • After trauma or surgery
  • In inflammation
  • On the surface of atherosclerotic plaques when they break open
• Platelets adhere to exposed von Willebrand factor/factor VIII complex, and if blood flow is slow, a thrombus will form

Flow and Thrombosis

• Abnormal blood flow (slow or turbulent) gives platelets a better chance to stick to the endothelium and clotting factors a chance to accumulate
• Thrombosis is more frequent in veins due to slower flow and the formation of eddies and pockets of stagnant blood

Propagation

• Progressive spread of thrombosis
• Original thrombus is a risk factor for propagation

Organisation

• Ingrowth of fibroblasts and small capillaries (similar to granulation tissue)
• Lumen remains obstructed
• Scar formation takes place (thrombus changes to scar tissue)

Recanalisation

• Occurs by the ingrowth of new small vessels
• The new vessels join up to restore blood flow, at least partially

Embolisation

• Caused by fragmentation of the thrombus
• Results in infarction at a distant site
• Embolisation doesn't happen in veins as the diameter of veins increases as you get closer to the heart, so embolism can still travel through

Thrombo-emboli

• From systemic veins: pass to the lungs to form pulmonary emboli
• From the heart: pass via the aorta to renal, mesenteric, and other arteries
• From atheromatous carotid arteries: pass to the brain to cause stroke
• From atheromatous abdominal aorta: pass to arteries of the legs

Effects of Thrombosis

• The most common clinical effects include:
  • Occlusion of an artery at the site of the thrombus resulting in ischaemia and infarction
  • Embolisation of part of the thrombus resulting in occlusion of an artery distant to the site of the thrombus
  • Congestion and oedema in the venous bed resulting in pain and sometimes skin ulceration
  • Repeated miscarriages due to thrombosis of the uteroplacental vasculature

Appearance of Thrombi

• Arterial:
  • Pale
  • Lines of Zahn (alternating lines of pink and white/yellow)
  • Lower cell content
• Venous:
  • Soft
  • Red (due to RBCs)
  • Gelatinous
  • Higher cell content

Outcome of Thrombosis

• Lysis: the thrombus is dissolved
• Propagation: the thrombus grows
• Organisation: the thrombus undergoes fibrous repair and forms a fibrous scar on the wall of the vessel
• Recanalisation: happens in an occluding thrombus, new channels lined with endothelium run through the occlusion and restore blood flow
• Embolisation: a part of the thrombus breaks off and embolises