Pathology
Thrombosis / Atherosclerosis
Platelets
- 4 layered
- Peripheral zone:
- Rich in glycoproteins and platelet factor 3 for adhesion and aggregation
- Sol-gel zone
- Microtubules and microfilaments to maintain discoid shape
- Organelle zone
Alpha granules and others containing mediators of clotting (factor VIII related antigen, factor V, fibrinogen, fibronectin, platelet-derived growth factor, chemotactics)
- Inner membrane zone
- Dense tubular system for contractility and prostaglandin synthesis
Thrombosis
Endothelial collagen and fibrin exposure leads to platelet adhesion to endothelium via glycocalyx signalling
Calcium is released from platelets dense tubular system leading to their degranulation (releasing factor V and fibrinogen which form thrombin via the coagulation cascade)
- Aggregation is stimulated by ADP and thrombin: platelets form a clump
- Note: aggregation is stimulated by thromboxane A2 and inhibited by prostaglandin I2.
- Inhibition of thrombosis:
- Protein C: vitamin-K dependent inhibitor of factors Va and VIIIa.
Clinical Correlate
Diseases of protein C function
- Protein C deficiency is autosomal dominant trait
Factor V Leiden leads to resistance of factor V to activated protein C (may contribute to 12% of patients with CRVO)
- Protein S and phospholipid are cofactors in factor Va and VIIIa deactivation.
- Protein S deficiency is autosomal dominant
- Antithrombin III inhibits numerous activated coagulation factors
- Thrombi may:
- Break and form emboli
- Be lysed by plasmin
Persist and organise (flow may be re-established by collateralisation/recanalisation)
Retinal emboli
- Most commonly originate from an atheromatous plaque at the carotid bifurcation
- Cholesterol (Hollenhorst plaque)
- Calcium: tend to cause more extensive pathology: BRAO, CRAOs
- Platelets: fibrin-platelet emboli cause TIAs
- Bacteria/vegetations: infective endocarditis
Atherosclerosis
- Endothelial damage
- Platelet adherence to injured endothelium
- Intimal smooth muscle proliferation in response to platelet-derived growth factor
Lipid accumulation intra- (macrophages become foam cells) and extracellularly (lipid within the arterial wall)