Venous Thromboembolism-1

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Venous Thromboembolism-1
Dr. Abdelaty Shawky Mohamed Assistant professor
of pathology
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Topics

• 1. Pathophysiology of VTE.
• 2. Clinical presentation of VTE.
• 3. Investigations of VTE.

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1. Pathophysiology of VTE
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Hemostasis and Thrombosis

• Hemostasis is the physiologic process that
  maintains the blood in a fluid state in normal
  vessels and to induce a rapid and localized
  hemostatic plug at a site of vascular injury to
  stop bleeding.

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• Thrombosis is the pathologic process opposite to
  hemostasis it can be considered an inappropriate
  activation of normal hemostatic processes,
  resulting in the formation of a (thrombus) in
  uninjured vessel or after minor injury.

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• Both hemostasis and thrombosis are regulated by
  three general components.
• 1. The vascular endothelium.
• 2. Platelets.
• 3. The coagulation cascade.

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• Q. What is the role of endothelial cells in
  hemostasis and thrombosis?

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• Endothelial cells have both antithrombotic
  activities preventing thrombosis in normal blood
  vessel and also have prothrombotic activities
  favoring thrombosis in injured blood vessels.
• The balance between endothelial antithrombotic
  and prothrombotic activities critically
  determines whether thrombus formation,
  propagation, or dissolution occurs

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Antithrombotic Properties

• Antiplatelet effects by secretion of
  prostacyclin (PGI2) and nitric oxide. Both
  mediators are potent vasodilators and inhibitors
  of platelet aggregation.
• Anticoagulant effects These effects are mediated
  by
• a. Thrombomodulin receptors for (thrombin) to
  block its action and also to activate protein C
  which in turn inactivate factors V and VIII.
• b. Heparin-like molecules receptors for
  anti-thrombin III to block factors IX and X.
• c. Release of tissue factor inhibitor. These
  inhibit the coagulation pathway.

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• Fibrinolytic effects Endothelial cells
  synthesize tissue-type plasminogen activator
  (t-PA), promoting fibrinolytic activity to clear
  fibrin deposits from endothelial surfaces .

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Prothrombotic Properties

• Platelet effects
• - Endothelial injury leads to adhesion of
  platelets to the underlying extracellular matrix
  this is facilitated by endothelial production of
  von Willebrand factor (vWF), an essential
  cofactor for platelet binding to subendothelial
  collagen.

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• Procoagulant effects Endothelial cells
  synthesize tissue factor, which activates the
  extrinsic clotting cascade.
• Antifibrinolytic effects Endothelial cells also
  secrete inhibitors of plasminogen activator
  (PAIs), which inhibits fibrinolysis.

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Coagulation cascade
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Thrombosis
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• Definition of thrombosis
• - Formation of a solid mass composed of the
  circulating blood elements, inside CVS system
  (blood vessels or heart) during life.

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Causes of thrombosis

• - There are 3 major factors which predispose to
  thrombosis (Virchows triad)
• 1. Endothelial damage.
• 2. Slowing turbulence of blood flow.
• 3. Blood hypercoagulability.

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• 1. Endothelial damage
• - Endothelial damage may be
• a. Mechanical trauma, repeated tourniquet
• b. Inflammatory arteritis, phlebitis and
  endocarditis.
• c. Degenerative atherosclerosis, hypertension..
  
• - The injured endothelium becomes swollen with
  rough surface.

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• 2. Slowing turbulence of blood flow.
• - Occurs in
• Left atrium in mitral stenosis.
• Leg veins in varicose veins and bed-ridden heart
  failure patients.
• Inside aneurysmal sacs.

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• 3. Blood hypercoagulability
• I. Genetic (inherited)
• Mutation of factor V gene.
• Mutation of prothrombin gene.
• - In both conditions the resulting factor V and
  prothrombin are not prone to degradation and have
  a sustained thrombotic actions.

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• Protein C and protein S deficiency
• These are natural anti-coagulant proteins.
• Their deficiency leads to hypercoagulability
  state.

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• II. Acquired
• Prolonged bed rest or immobilization.
• Myocardial infarction.
• Tissue damage (surgery, fracture, burn).
• Cancer.
• Oral contraceptive pills.

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Pathogenesis (Mechanism) of thrombosis

• Endothelial injury leads to
• 1. Exposure of sub-endothelial collagen promote
  platelet aggregation.
• 2. Release of tissue factor promote fibrin
  formation.

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• I. Exposure of sub- endothelial collagen
• a. Platelets adhesion to the exposed collagen
  (this is mediated by factor VIII released from
  endothelial cells).
• b. Platelet activation and release of Thromboxane
  A2 (potent vasoconstrictor and induce platelet
  aggregation)

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• II. Release of the tissue factor (from
  endothelial cells) that stimulate the coagulation
  cascade to form thrombin that convert fibrinogen
  into fibrin.
• The end result is fibrin network entangling
  aggregated platelet (Thrombus)

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• The lumen of blood vessel is occupied by a red
  mass which is adherent to the vessel wall at an
  area called the head of the thrombus .

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Gross picture of the thrombus
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Microscopic picture of thrombus
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• These are "lines of Zahn" which are the
  alternating pale pink bands of platelets with
  fibrin and red bands of RBC's forming a true
  thrombus.

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Thanks