Coagulation Flashcards
How do endothelial cells keep blood kept liquid in a healthy person?
1) Secrete antiplatelet-aggregation factors NO, prostacyclin and ADP dephosphatase + acting as barrier to ECM
2) Express heparin sulfate which activates antithrombin III to cut thrombin, Xa and IXa
3) Express thrombomodulin which makes thrombin activate protein C which digests Va and VIIIa
4) Produce tPA which activates plasminogen -> plasmin, fibrin cutter
What is the definition of coagulation?
Coagulation is a property of plasma whereby a cascade results in conversion of soluble fibrinogen protein to insoluble fibrin strands
Some facts about platelet size and lifespan?
Platelets are tiny cells with no nuclei - 2-3 microns in diameter (1/3 that of RBC
Platelets lifespan in 8-10 days
What are the three steps in preventing bleeding?
1) Vasocontriction
2)
3)
How is vasoconstriction mediated after vessel injury?
Neurogenic reflex
Myogenic reflex
Endothelin released by injured endothelial cells
How does platelet adhesion occur?
Injured endothelial cells produce vW factor, which acts as glue between exposed collagen of ECM and the GP1b receptors on platelets
What happens when vW factor binds to GP1b on platelets?
Platelets are activated -
PL - Arachidonic acid -> thromboxane A2
What is thromboxane A2?
Vasoconstrictor and platelet aggregator
I.e. Opposite of PGI2 (prostacyclin) produced by healthy endothelial cells - concept that they are kept in balance
How does aspirin work to thin the blood?
Aspirin inhibits COX to prevent AA -> TxA2!
So platelets lose ability to aggregate
What about the release rxn?
Once activated by vWF (in addition to TxA2 production), platelets release granules
Delta sac - serotonin vasoconstrictor, ADP platelet activator, and Ca2+ catalyst for coag factor rxns!
Alpha granules - coag factors V, VIII, fibrinogen and PDGF stimulator of smooth muscle mitosis and fibroblasts
Tell me more about the role of Ca2+ released from platelets
Coag factor rxns occur on surface of platelets, facilitated by binding with Ca2+ - they are negatively charged due to gamma carboxylation of glutamic acid residues, which is dependent on Vit K!
So vitamin K antagonists -
Prevent gamma carboxylation of glutamic acid on coag factors, preventing their approximation and reaction due to calcium binding
How does clopidogrel work?
It blocks platelet ADP-receptors, preventing activation and aggregation
How is the primary haemostatic plug formed?
Platelet activation and aggregation due to release rxn results in formation of the primary plug
What is the difference between the intrinsic and extrinsic pathways?
Intrinsic is from factor XII - within the blood
Extrinsic is from TF released by injured endothelial cells
Both pathways result in production of thrombin –> conversion of fibrinogen to fibrin monomers, and their cross linking by TSF to produce the secondary haemostatic plug
