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• Arterial thrombosis


  • Main features
  • Appropriate drugs to treat
• Platelet activation when forming a platelet plug

  3 stages
• Components of Virchow's Triad


  • 1 example of each
• Thrombosis

  Pathological formation of an intravascular blood clot
• Thrombosis

  • Can occur in a vein or an artery
  • Characterised by the Lines of Zahn (if large vessel) & attachment to a vessel wall (both features can be used to distinguish thrombus from post mortem [PM] clot)
• Thrombosis


  • Splenic artery aneurysm– showing lines of Zahn
• Virchow's Triad


  Things that cause thrombosis
• Components of Virchow's Triad


  • Disruption of blood flow (stasis)
  • Endothelial cell damage
  • Hypercoagulable states
• Disruption of blood flow

  • Immobilisation (flight, bedrest)
  • Cardiac wall dysfunction (mural thrombus post MI)
  • Aneurysm
  • Atrial Fibrillation
  • Left atrial dilation due to mitral stenosis
• Endothelial cell damage


  • Atherosclerosis – ruptured plaque
  • Vasculitis of any cause
  • High levels of homocysteine (caused by vitamin B12 or folate deficiency)
  • Turbulent blood flow at arterial bifurcation
  • Oxidized LDL
  • Cigarette smoke
  • Cytokines
• Hypercoagulable states


  • Due to excessive procoagulant factors or defective anticoagulant
  • May be inherited (AT3 deficiency) or acquired (DIC)
  • Classic presentation is recurrent DVTs or DVTs at a young age (other sites are hepatic or cerebral veins)
• Venous thrombosis


  • Most common cause is stasis of blood
  • Most common site is deep veins of the lower limb (most commonly below the knee)
  • Red, swollen, painful leg with skin discoloration
  • Can dislodge to the lungs causing a pulmonary embolism
• Treatment for venous thrombosis


  • Warfarin, or other anticoagulant eg. Rivaroxaban, Apixaban
  • They do not dissolve clot they prevent further formation
  • The fibrinolytic system breaks down the clot
• Arterial thrombosis


  • Most commonly due to endothelial damage related to turbulent blood flow at bifurcation or over atherosclerotic plaques in high velocity vessels
  • In some cases they are mixed thrombi composed of platelets and with RBCs held together by fibrin - lines of Zahn
  • Hypercoaguability and stasis are rare causes of arterial thrombosis
  • Arterial thrombi are adherent and may be occlusive
  • Grey/white fibrin clot primarily composed of platelets
• Treatment for arterial thrombosis


  Inhibitors of platelet aggregation prevent their formation – e.g. aspirin
• Arterial thrombosis


  • MI, small bowel infarction, stroke
• Stages of platelet activation

  1. Adhesion

  2. Release reaction

  3. Aggregation
• Platelet activation


  • Platelets undergo shape change and degranulate: release mediators ADP (from dense core granules), Thromboxane A2 (TXA2) - a derivative of platelet cyclooxygenase, Calcium
  • ADP induces the expression of GP2b/3a (GPIIb/IIIa) (another essential receptor for aggregation of platelets) and fibrinogen which acts as a linker molecule in the developing clot
  • TXA2 is a vasoconstrictor that also promotes platelet aggregation
• Thrombin


  • Acts on Fibrinogen to produce Fibrin monomers
  • Activates fibrin stabilising factor 13 (13a) to convert these monomers to cross-linked fibrin, strengthening the blood clot
  • Acts in a feedback loop to activate several other coagulation factors and is therefore pivotal in the amplification system
  • Thrombin itself is switched off by the natural anticoagulant antithrombin3, limiting clot formation
• Plasmin


  • Breaks down clot by cleaving fibrin and fibrinogen into fibrinogen degradation products (FDPs) which form fragments known as D-dimers
  • Degrades some clotting factors
  • Blocks platelet aggregation