10. Coagulation and Haemostasis Flashcards
Ultrastructure of Platelets
α granule
electron-dense granules
microfilaments
Open canalicular system
Dense tubular system
mitochondrion
Plasma membrane
GP Ia/IIa
binds to collagen
stops platelet migration along endothelial cells
GP IIb/IIIa
binds vWF and fibrinogen
Links endothelium and other platelets
Defective in Glanzmann’s Thrombasthenia
Platelet release reaction
Collagen exposure
discharge of platelet granules and electron-dense granules
Lasts several minutes
Release of substances involved in coagulation+ vasoconstriction
Contents of α granules
PDGF
thromboglobulin
Fibrinogen
Clotting factors
vWF
Contents of electron-dense granules
ADP, ATP
Serotonin, Calcium
Platelet aggregation
Occurs at vascular injury site
promoted by ADP and thromboxane A2
Platelets swell and aggregate
more granule release reaction
positive feedback process.
Tissue factor
Integral membrane protein
Forms high affinity complex with VIIa
generates explosive thrombin generation
Thrombin Generation
Xa activates V
formation of prothrombinase complex
Small amounts thrombin generated
Inhibitors of coagulation
1) Local inhibition
2) Naturally occuring anticoagulants
3) Fibrinolytic system
Local Inhibition
TFPI inhibits VIIa, Xa, tissue factor
Antithrombin Limits thrombin at site of injury
Enhanced by heparin
Naturally occuring anticoagulants
Fibrinolytic system
endothelium: Pro-haemostasis
Secrete tissue factor → initiates coagulation
Secrete vWF → carries FVIII, collagen-platelet binding
endothelium: Anti-haemostasis
Secrete prostacyclin and nitric oxide → ↓platelet aggregation, promote vasodilatation
Secretes antithrombin, proteins C&S, TFPI → anticoagulation
Provides thrombomodulin
Secrete tPA → fibrinolysis
Coagulation Cascade
