Blood Platelets and Haemostasis

Blood Platelets (Thrombocytes)

• Small, round or oval discs formed in the bone marrow
• Formed from megakaryocytes, large cells that fragment into platelets
• Lack nuclei and cannot reproduce
• Life span: 8 days in the blood
• Count: 250,000 to 500,000 cells per cubic millimeter (cmm)
• Removed from circulation by tissue macrophages

Functions of Platelets

• Contractile proteins (actin and myosin): Cause platelets to contract for clot retraction
• Granules: Secreted upon activation, including serotonin and ADP
• Clotting factors and Platelet-derived Growth Factor (PDGF): Vital for wound healing
• Mitochondria and enzymes: Synthesize ADP and ATP

Haemostasis

• Prevents blood loss, or stops bleeding
• Process that occurs to stop bleeding from wounds

Stages of Haemostasis

• Local Vascular Spasm:

  • Immediate contraction of blood vessel wall in response to injury
  • Triggered by:
    • Nervous reflexes from pain
    • Local myogenic contraction of vessel
    • Factors released from damaged tissue and platelets
  • Platelets contribute by releasing thromboxane A and serotonin - vasoconstrictors
  • Can last minutes to hours, allowing time for platelet plugging and blood coagulation

• Platelet Plug Formation:

  • Adherence:

    • Platelets come into contact with exposed collagen fibers (underneath the endothelium)
    • Platelets change shape and become sticky

  • Activation:

    • Platelets release ADP, thromboxane A, serotonin, lysosomal enzymes, and platelet factors
    • These substances activate nearby platelets

  • Aggregation:

    • Activated platelets stick to collagen fibers and to each other, forming a platelet plug
    • Can stop bleeding if the vessel opening is small

• Blood Clot Formation:

  • Prothrombin Activator:
    • Formed in response to injury
    • Initiates the coagulation cascade (series of steps leading to clot formation)
  • Extrinsic Pathway:
    • Starts with trauma to the vascular wall and surrounding tissues
  • Intrinsic Pathway:
    • Starts within the blood itself
  • Thrombin:
    • Prothrombin activator converts prothrombin to thrombin
  • Fibrin:
    • Thrombin acts as an enzyme to convert fibrinogen into fibrin threads
    • Fibrin threads create a network that traps blood cells (forming the clot)

Role of Vitamin K in Blood Clotting

• Required for the liver to synthesize four crucial clotting factors: Factor II (prothrombin), VII, IX, and X
• Deficiency of Vitamin K leads to:
  • Deficiency of the clotting factors
  • Increased risk of bleeding

Platelets' Role in Clot Retraction

• Platelets bind to fibrin threads, linking them together
• Secrete fibrin stabilizing factor (factor XIII) for further cross-linking
• Contain contractile proteins that are activated by thrombin and calcium ions
• This causes the clot to contract, pulling the edges of the broken vessel closer

Course of the Clot

• Possible Outcomes:
  • Invasion by fibroblasts that form connective tissue (scarring)
  • Dissolution (lysis)

Lysis of Blood Clot

• Plasminogen (profibrinolysin):
  • A plasma protein that is converted to plasmin (fibrinolysin)
  • Plasmin degrades fibrin and other clot components
• Plasminogen Activators:
  • Factors released from injured vascular endothelium and damaged tissue
  • Activate plasminogen

Fibrin Degradation Products

• Fragments of fibrin produced by plasmin
• Help regulate further clot formation

Factors Preventing Normal Coagulation

• Rapid blood flow: Prevents platelets from sticking and breaking down
• Healthy vascular endothelium: Smooth surface prevents contact with clotting factors
• Inactive clotting factors: Clotting factors circulate in inactive forms
• Liver removal of activated factors: Liver removes activated coagulation factors from circulation
• Anti-thrombin III:
  • A plasma protein that inactivates thrombin
• Heparin:
  • A natural anticoagulant found in small amounts

Factors Promoting Intravascular Thrombosis

• Endothelial damage: e.g., atherosclerosis or trauma
• Slow blood flow: e.g., prolonged bed rest
• Increased blood viscosity or platelet count: e.g., after surgery
• Smooth endothelium: One of the most important factors in preventing clotting
• Roughed endothelium: Initiates clotting reactions

Anticoagulants

• Substances that inhibit or prevent blood clotting

Types of Anticoagulants

• In Vitro Anticoagulants (Outside the body):

  • Oxalate compounds:
    • Precipitate calcium oxalate (Ca++), reducing calcium levels to inhibit clotting.
    • Toxic, not used for blood transfusions
  • Citrate compounds:
    • Combine with Ca++ to form calcium citrate.
    • Not toxic, used for blood transfusions (blood banks)
  • Siliconized containers:
    • Prevent blood from sticking to surfaces
  • Heparin:
    • Prevents clotting both inside and outside the body

• In Vivo Anticoagulants (Inside the body):

  • Heparin:

    • A natural anticoagulant produced by mast cells
    • Used in medical practice
    • Administered intravenously or subcutaneously
    • Mechanism of Action:
      • Increases the activity of anti-thrombin III, which inactivates thrombin
      • Forms a complex with anti-thrombin III (anti-thrombin-heparin co-factor) to:
        • Remove thrombus
        • Remove other activated clotting factors
      • Stimulates fibrinolysis (breakdown of clots)
    • Immediate effect when given intravenously

  • Coumarin Compounds (Oral anticoagulants):

    • Dicumarol and warfarin
    • Mechanism of Action:
      • Inhibit vitamin K, preventing the liver from synthesizing clotting factors II, VII, IX, and X
    • Oral administration
    • Effect takes 2 days to appear (due to existing clotting factors in the plasma)

Hemorrhagic Disorders

• Excessive bleeding due to deficiencies in clotting factors or platelets

Vitamin K Deficiency

• Contributes to hemorrhagic disorder
• Causes insufficiency of clotting factors II, VII, IX, and X
• Resulting from:
  • Poor fat absorption from the gastrointestinal tract
  • Liver failure to secrete bile (obstructive jaundice, hepatitis C or B), which prevents fat digestion and vitamin K absorption