Thrombosis

Overview
  • Thrombosis refers to the formation of a thrombus (blood clot) due to dysregulation of normal hemostasis. Certain factors can favor thrombus formation in the venous system, arterial system, or both.
Pathogenesis
  • Overview
    • The large variety of factors which can cause dysregulated activation of hemostasis have been organized into three broad categories. These categories, detailed below, were named after the pioneering German physiologist Rudolf Virchow and are fondly known as "Virchow's Triad".
  • Endothelial Dysregulation:
    • As described in hemostasis, the endothelium plays a key role in the regulation of clotting. Acquired conditions that lead to endothelial dysregulation can lead to inappropriate thrombosis. These conditions often do not lead to outright endothelial injury but may subtly dysregulate endothelial control of hemostasis in such a way as to increase the probability of thrombus formation.
    • Examples include:
  • Blood Flow Dysregulation
    • Normal blood flow occurs in a laminar fashion such that platelets tend to travel in the center of vasculature, thus reducing their contact with the vascular wall. Furthermore, smooth, laminar flow reduces stress on the endothelium. Finally, blood flow constantly mixes the plasma contents, maintaining the fine-tuned balance between pro- and anti-coagulant factors. Dysregulation of blood flow, either due to stasis or turbulent flow of blood, can affect all of these processes and thus promote inappropriate coagulation. Stasis of blood can increase contact between platelets and the vascular wall as well as allow localized imbalances in pro- and anti-coagulant factors within the plasma. Turbulent flow can also increase contact between platelets and the vascular wall as well as promote endothelial stress and thus endothelial dysregulation. Static blood may be found in aneurysms, dilated atria, or adjacent to non-contractile myocardium after a myocardial infarction. Blood stasis may also be observed in the veins of extremities that are long in a position of dependence, resulting in venous thrombosis, or in those with highly viscous blood due to polycythemia vera. Turbulent flow of blood is often found in those with hypertension.
  • Hypercoagulable States
    • Refers to any acquired or genetic disorders which either enhance the activity of pro-coagulant factors or suppress the activity of anti-coagulant factors. Genetic hypercoagulable disease are generally highly specific and usually affect a single protein within the coagulation. Alternatively, how acquired disease states affect the activity of coagulation factors is usually not well-understood.
    • Genetic Hypercoagulable Disease include:
      • Factor V and Prothrombin Mutations
      • Protein C or Protein S Deficiency
    • Acquire Hypercoagulable Disease include
      • Patients with malignancies or who have undergone recent surgery/trauma
      • Patients with Disseminated Intravascular Coagulation or antiphospholipid syndrome
      • Oral Contraceptive Pill users especially if smoking
Morphology