PRIMARY

• Concept of Normal Coagulation

  • In the absence of an injury, regulatory proteins or inhibitors prevent the formation of clots
  • Normal hemostasis is a balance between clot formation and clot dissolution
  • Imbalances lead to bleeding or thrombosis
  • Deficiencies in clotting factors lead to bleeding
  • Deficiencies in certain inhibitors lead to thrombosis
• Overview of Hemostasis


  • Simultaneous and complex process of making sure that our blood stays on its liquid state
  • Normal hemostatic mechanism involves activating necessary components like platelets and clotting factors to form a clot and stop bleeding
  • Clot should be removed once the injury is repaired to prevent blockage of blood flow
• Primary Hemostasis


  Series of complex processes by which the body spontaneously stops bleeding and maintains blood on its fluid state within the blood vessel compartment
• Elements of Hemostasis


  1. Extravascular Tissue Factor/TF: Contains thromboplastin or tissue factor which activates clotting factors to form thrombin

  2. Vascular Intima: Contains endothelial cells critical to hemostasis, helps in clot formation, clot dissolution, and prevention of clot formation
• Excessive collagen could result in keloid formation
• To synthesize collagen, an important source is Vitamin C which can be better absorbed from fruits and vegetables
• Primary Hemostasis

  • Rapid, short-lived response
  • Involves vascular intima and platelets
• Secondary Hemostasis


  • Delayed, long-term response
  • The activator, tissue factor, is exposed on cell membranes
• Primary Hemostasis

  1. Refers to the role of blood vessels and platelets in response to a vascular injury

  2. Main activities include vessel constriction and platelet activation
• Primary Hemostasis

  • Activated by desquamation and small injuries to blood vessels
  • Involves vascular intima and platelets
• Cellular elements of hemostasis (intravascular)

  Referring to platelets and other components circulating in the plasma critical in hemostasis like clotting factors and inhibitors
• Secondary Hemostasis

  • Activated by large injuries to blood vessels and surrounding tissues
  • Involves platelets and coagulation system
• Intravascular Component

  • Platelets
  • Plasma proteins (inhibitors)
• Tunica Intima


  • Innermost layer where endothelial cells are located
  • Provides a barrier for platelets against internal components, especially collagen
• Blood vessels

  • Contain three different layers: Tunica Intima, Tunica Media, Tunica Adventitia
• Tunica Media


  • Thickest coat where collagen is found
• Tunica Adventitia


  • Outer layer where collagen is found
  • Helps supply nutrients to the tissues in blood vessel wall
• Vascular Intima


  • Provides the interface between circulating blood and body tissues
  • Endothelial cells play a role in immune response, vascular permeability, proliferation, and hemostasis
• Diapedesis allows white cells to leave blood vessels without causing damage in case of injury, infection, or inflammation
• End point of vascular injury

  Platelets aggregate with one another to form a clot
• Clotting factor


  Highlighted for the action or activity of platelets
• Endothelial cells


  Promote adhesion of WBCs to eliminate particular microorganisms
• Everything needed in hemostasis

  • Platelets
  • Inhibitory cell
  • Activation of platelets
  • Blood vessel
  • Collagen
  • EC
  • Anticoagulant properties
  • Procoagulant properties
• Fibroblasts


  Help initiate the formation of new vessels (angiogenesis) to facilitate repair and healing of damaged sites
• Components of blood vessels

  • Fibroblasts
  • Smooth muscle cells
• Microorganisms can cause injury to the vessels
• Action or activity of platelets

  Repairing to blood
• Procoagulant properties of damaged vascular intima

  • VWF essential for platelet attachment
  • P-selectin facilitates platelet adhesion
  • ADAMTS-13 ensures platelets and VWF interaction remain localized
  • Collagen exposed activates platelets and CF
  • PAI-1 inhibits fibrinolysis
  • TAFI inhibits fibrinolysis
• Smooth muscle cells in arteries


  Contract vessels during primary hemostasis if there is an injury
• Anticoagulant properties of intact vascular intima

  • Phospholipid broken down to form arachidonic acid
  • Arachidonic acid undergoes cyclooxygenase pathway to form prostacyclin
  • Prostacyclin can dilate vessels and inhibit platelet activation
  • Nitrous oxide relaxes smooth muscles and promotes angiogenesis
  • Heparan sulfate inhibits thrombin
  • Thrombomodulin inhibits thrombin
  • EPCR inhibits thrombin
  • TFPI inhibits activation of CF
  • TPA converts plasminogen to plasmin for clot destruction
• Procoagulant Properties of the Damaged Vascular Intima

  • Smooth muscle cells in arterioles and arteries induce vasoconstriction
  • Exposed subendothelial collagen binds VWF and platelets
  • Damaged or activated ECs secrete VWF, secrete adhesion molecules: P-selectin, ICAMs, PECAMs
  • Exposed smooth muscles and fibroblasts have tissue factor exposed on cell membranes
  • ECs in inflammation have tissue factor induced by inflammation
• Thrombin-activatable fibrinolytic inhibitor (TAFI)


  Inhibits fibrinolysis, ensures clot formation, secreted by endothelial cells when activated by thrombin, cleaves large VWF multimers
• Platelet Response

  Formation of a Platelet Plug, Adhesion, Shape change, Aggregation, Release reaction and Stabilization
• Platelets bind on damaged vessel walls
• Fibrinolytic Properties of Vascular Intima

  Endothelial cells secrete TPA (Tissue Plasminogen Activators), provide inhibitors to prevent excessive plasmin generation: PAI-1 (Plasminogen Activator Inhibitor), TAFI (Thrombin-activatable fibrinolytic inhibitor)
• ICAMs stand for intercellular adhesion molecules
• PECAMs stand for platelet endothelial cell adhesion molecules
• Platelet Adhesion


  The property by which platelets bind non-platelet surfaces, VWF links platelets to collagen
• Platelets should contain specialized proteins like glycoprotein Ib, glycoprotein IX, or glycoprotein V to attach on VWF
• Deficiency in glycoprotein Ib, glycoprotein IX, or glycoprotein V leads to Bernard Soulier syndrome