Blood Platelets and Haemostasis

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

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)

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

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

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

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

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

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)

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