Platelet function and morphology

Definition: Platelets (thrombocytes) are small, anucleated blood cells involved in clotting.
Size: Approximately 3 μm in diameter, 1 μm in thickness.
Life Span: They have a life span of 7-10 days.
Shape: Inactive platelets resemble "plates".

Normal Range: Platelet count (PLT) suggests blood’s ability to clot:
- Males and females: 150-450 x 10^3 /μL.
Components: Distinction between plasma and serum is important in diagnostics.

Origin: Platelets are derived from megakaryocytes (MKs), which are formed in the bone marrow from pluripotent hematopoietic stem cells.
Process:
- MKs fragment in the bone marrow to release small platelet fragments into circulation.
- MK undergoes several DNA replications without division.
- Size comparison: MKs are 30-50 μm, while platelets are 2-4 μm.
- One MK releases approximately 3,000 platelets.
Regulation: Thrombopoietin (TPO) regulates MK growth and maturation. It is primarily produced in the liver.

Structure:
- No nucleus and consist of a plasma membrane.
- Membrane changes during activation influenced by phosphatidylserine (PS).
Receptors:
- Glycoproteins (GP):
  - GP Ia/IIa and VI: bind collagen for adhesion.
  - GP Ib: binds von Willebrand factor for adhesion.
  - GP IIb/IIIa: binds fibrinogen for aggregation.
- Protease activated receptor-1 (PAR1): binds thrombin for activation.
- TXA2 receptor (TP): binds thromboxane A2 for activation.
- P2Y12 receptor: binds ADP for activation.

Dense Tubular System (DTS): Closed channel for calcium storage.
Surface-Connected Canalicular System (SCCS): Open system that allows for increased surface area during activation and discharge of granules.

Components: Includes actin, myosin, and thrombosthenin.
Functions:
- Supports plasma membrane and maintains disc shape of inactive platelets.
- Mediates rapid shape change during activation.

Types:
- Dense Granules: 2-10 per platelet, containing ADP/ATP, calcium, serotonin.
- Alpha-Granules: 20-200 per platelet, containing growth factors (PDGF), chemokines (PF4), adhesive proteins, coagulation factors, and anti-lytic factors (PAI1).

Gray Platelet Syndrome (GPS):
- Characterized by large platelets and gray appearance under microscopy.
- Results in thrombocytopenia and mild/moderate bleeding tendency; autosomal recessive disorder.
Von Willebrand Factor (vWF):
- Synthesized in endothelial cells and megakaryocytes; stored in Weibel-Palade bodies and alpha-granules.
- Functions in binding collagen and mediating platelet aggregation.
Von Willebrand Disease:
- Bleeding disorder due to deficiency of vWF.
- Symptoms include excessive bruising and prolonged bleeding.
Thrombotic Thrombocytopenic Purpura (TTP):
- Due to absence of ADAMTS13; results in large vWF multimers leading to thrombosis and platelet consumption.

Heamostasis and Thrombosis: Main role is the formation of the platelet plug through:
- Steps: Adhesion > Activation > Secretion > Aggregation.
- Secretion: Releases procoagulant factors, vasoconstrictors, TXA2 for wound healing.
- Monitoring: Platelets monitor vessel integrity by maintaining proximity to the vessel wall.

Triggered by injury to the vascular wall exposing subendothelial collagen.
Von Willebrand Factor (vWF) adheres to collagen and binds GP Ib to recruit platelets.

Inactive vs. Activated State:
- Inactive: Disk-shaped.
- Activated: Spherical with spiky projections (pseudopods).
Mechanism:
- Increases intracellular Ca2+, leading to scramblase activation that translocates PS to the outer membrane for procoagulant activity.

Secretion Mechanism: Granules discharge contents (e.g., ADP, TXA2) during shape change to promote secondary hemostasis.
Aggregation: Interaction between activated platelets requiring Ca++ and ATP via GP IIb/IIIa, initiated by various agonists (collagen, thrombin, ADP).
Inhibition: Counteracted by prostacyclin and nitric oxide.