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Hematology

Vascular System

Overview of the Vascular System in Hemostasis

  • Definition: The vascular system, comprised of arteries, veins, and capillaries, is much more than just a network of pipes. It plays a dynamic and integral role in maintaining hemostasis, both at rest and in response to injury
  • Key Roles:
    • Provides a physical barrier to prevent blood loss after injury
    • Regulates blood flow to the site of injury
    • Releases substances that activate platelets and coagulation factors
    • Inhibits coagulation to prevent excessive clot formation
    • Participates in fibrinolysis to remove clots after tissue repair
  • Components:
    • Endothelial Cells: The inner lining of blood vessels
    • Subendothelial Matrix: Located beneath the endothelial cells, containing collagen, von Willebrand factor (vWF), and other substances

Endothelial Cells: The Gatekeepers of Hemostasis

Endothelial cells are the key regulators of hemostasis. They have both procoagulant and anticoagulant properties, maintaining a delicate balance to prevent both bleeding and thrombosis

  • Intact Endothelium (Antithrombotic Properties):

    • Physical Barrier:
      • Provides a smooth, non-thrombogenic surface that prevents platelets and coagulation factors from adhering to the vessel wall
    • Inhibition of Platelet Activation:
      • Production of Prostacyclin (PGI2): PGI2 is a vasodilator and inhibits platelet activation and aggregation
      • Production of Nitric Oxide (NO): NO is a vasodilator and inhibits platelet adhesion and aggregation
      • CD39 (Ecto-ADPase): Degrades ADP, a potent platelet activator
    • Inhibition of Coagulation:
      • Thrombomodulin: Binds to thrombin, converting it from a procoagulant to an anticoagulant enzyme that activates Protein C. Protein C then inhibits Factors Va and VIIIa
      • Heparan Sulfate: Binds to antithrombin, enhancing its ability to inhibit thrombin and other coagulation factors (IXa, Xa, XIa, XIIa)
      • Tissue Factor Pathway Inhibitor (TFPI): Inhibits the Tissue Factor-VIIa complex, preventing the initiation of the extrinsic pathway of coagulation
    • Promotion of Fibrinolysis:
      • Tissue Plasminogen Activator (tPA): Released by endothelial cells to activate plasminogen and promote fibrinolysis

  • Injured Endothelium (Procoagulant Properties):

    • Exposure of Subendothelial Matrix:
      • Damage to the endothelium exposes the underlying subendothelial matrix, which contains collagen and von Willebrand factor (vWF)
      • Collagen: Activates platelets and initiates the intrinsic pathway of coagulation
      • vWF: Binds to platelet GPIb/IX/V, mediating platelet adhesion to the damaged vessel wall
    • Tissue Factor (TF) Expression:
      • Endothelial cells express tissue factor (TF) on their surface upon activation by inflammatory cytokines or other stimuli
      • TF initiates the extrinsic pathway of coagulation
    • Inhibition of Natural Anticoagulants:
      • Damaged endothelial cells reduce their production of thrombomodulin, heparan sulfate, and TFPI, diminishing their anticoagulant properties
    • Release of Platelet Activating Factors:
      • von Willebrand Factor (vWF): vWF is released from Weibel-Palade bodies in endothelial cells
      • Platelet Activating Factor (PAF): Some endothelial cells can synthesize and release PAF

The Subendothelial Matrix: A Scaffold for Hemostasis

The subendothelial matrix is a complex layer located beneath the endothelial cells that contains various proteins and substances that play a crucial role in hemostasis

  • Collagen:

    • Provides a surface for platelet adhesion and activation
    • Binds to platelet glycoprotein VI (GPVI), initiating intracellular signaling pathways that lead to platelet activation and aggregation
    • Also activates the intrinsic pathway of coagulation by activating Factor XII

  • von Willebrand Factor (vWF):

    • Binds to platelet GPIb/IX/V, mediating platelet adhesion to the damaged vessel wall
    • Especially important under high shear stress conditions, such as in small arteries and arterioles
    • Also binds to Factor VIII, protecting it from degradation

  • Other Components:

    • Fibronectin, laminin, and other adhesive proteins that contribute to platelet adhesion and cell migration

Regulation of Blood Flow: Vasoconstriction and Vasodilation

The vascular system regulates blood flow to the site of injury through vasoconstriction and vasodilation:

  • Vasoconstriction:

    • Immediate response to vascular injury
    • Reduces blood flow to the injured area, limiting blood loss and promoting platelet adhesion
    • Mediated by:
      • Endothelin-1: A potent vasoconstrictor released by endothelial cells
      • Thromboxane A2 (TxA2): Released by activated platelets
      • Nervous system reflexes

  • Vasodilation:

    • Occurs later in the hemostatic process to promote tissue repair and angiogenesis (formation of new blood vessels)
    • Mediated by:
      • Nitric Oxide (NO): Released by endothelial cells
      • Prostacyclin (PGI2): Released by endothelial cells
      • Vascular endothelial growth factor (VEGF): Promotes angiogenesis

Angiogenesis

  • Definition: The formation of new blood vessels from pre-existing vessels
  • Role in Hemostasis and Wound Healing:
    • Provides nutrients and oxygen to the healing tissue
    • Removes waste products
  • Regulation:
    • Vascular Endothelial Growth Factor (VEGF): The primary driver of angiogenesis
    • Other growth factors and cytokines: Also involved in regulating angiogenesis

Key Terms

  • Endothelial Cells: Cells that line the inner surface of blood vessels
  • Subendothelial Matrix: The layer beneath the endothelial cells, containing collagen and vWF
  • Tissue Factor (TF): A protein that initiates the extrinsic pathway of coagulation
  • Von Willebrand Factor (vWF): A protein that mediates platelet adhesion and carries factor VIII
  • Prostacyclin (PGI2): A vasodilator and inhibitor of platelet activation
  • Nitric Oxide (NO): A vasodilator and inhibitor of platelet adhesion
  • Thrombomodulin: An endothelial cell receptor that binds to thrombin and activates protein C
  • Tissue Factor Pathway Inhibitor (TFPI): An inhibitor of the TF-VIIa complex
  • Vasoconstriction: Narrowing of blood vessels
  • Vasodilation: Widening of blood vessels
  • Selectins: Adhesion molecules on endothelial cells that promote leukocyte rolling
  • Integrins: Adhesion molecules on leukocytes that mediate firm adhesion
  • Extravasation: The process by which leukocytes migrate from the bloodstream into tissues
  • Angiogenesis: The formation of new blood vessels