Haemostasis Flashcards
What are the 3 stages of the cell-based theory of coagulation?
- Initiation
- Amplification
- Propagation
Summarise the events of the initiation stage of coagulation
Small-scale production of thrombin on TF-bearing cells
Describe the mechanism by which TF triggers thrombin production
TF-bearing cells activate Factors X and V
FX and FV trigger formation of the prothrombinase complex
Prothrombinase complex activates factor II –> IIa (prothrombin –> thrombin)
What is the mechanism of action of antithrombin?
Inactivates thrombin (FIIa) and Factir Xa
What class of drugs targets the initiation phase of coagulation?
Anti-coagulants
Recall an example of a factor IIa inhibitor
Dabigatran
Recall an example of a factor Xa inhibitor
Rivaroxaban
Recall the mechanism of action of heparin
Activates antithrombin
Recall an example of a low-molecular weight heparin
Dalteparin
What is the mechanism of action of warfarin
Inhibits Vit K which is essential for generation of factors II, VII, IX and X
What is the main indication for anti-coagulant use?
VENOUS thrombi
Recall 3 examples of when anti-coagulant therapy may be used
DVT
Thrombosis during surgery
Stroke prevention in AF patients
Summarise the events of the amplification stage of coagulation
Large-scale production of thrombin on platelets, overwhelming anti-thrombin to lead to platelet activation
Recall the 2 ways in which PAR activation brings about platelet aggregation
- PAR activation –> rise in IC CA++. Ca++ –> ADP exocytosis from dense granules. ADP auto-activates platelets via ADP receptor called P2Y12 –> platelet aggregation
- PAR activation –> arachdionic acid production –> TXA2 generation –> GPIIb and GPIIIa expression –> platelet aggregation
Describe the biochemical mechanism by which thrombin triggers platelet-aggregation pathways
Binds to Protease-Activated-Receptor (PAR) on platelets
Give 3 examples of anti-platelet drugs
- Clopidogrel
- Aspirin
- Abciximab
Recall the mechanism of action of clopidogrel
ADP-receptor antagonist - prevents platelet activation + aggregation
Recall the mechanism of action of aspirin
Irreversible COX1 inhibitor - inhibits TXA1 production
Recall the mechanism of action of abciximab
Inhibits GPIIb/IIIa receptor –> inhibition of platelet aggregation
What is the main indication for anti-platelet drugs?
ARTERIAL thromboses
Differentiate the treatment strategies for NSTEMIs and STEMIs
NSTEMI: anti-platelet to reduce lipid accumulation + platelet aggregation
STEMI: need anti-platelet to reduce lipids and platelet aggregation as well as a thrombolytic to dissolve thrombus as it is bigger
Summarise the events of the propagation phase of coagulation
Thrombin-mediated generation of fibrin strands from circulatory fibrinogen
What is the normal physiological function of fibrin
Fibrin strands come together to form a net that holds clot together
What sort of drugs are used to target the propagation phase of coagulation
Thrombolytics - these can reduce a pre-formed clot
Within what time-frame are thrombolytics effective?
30 mins
Recall the general mechanism of action of thrombolytics
Activate plasmin from plasminogen, plasmin-protease degraded fibrin
Recall an example of a thrombolytuc drug
Alteplase = recombinant plasminogen activator
Recall 2 possible occasions when thrombolytics might be used
First-line treatment for stroke
ST-elevated MI (STEMI)
Recall 4 examples of pro-coagulant clotting factors in plasma
Prothrombin
Factor V
Factor VII
Fibrinogen
Recall 4 examples of anti-coagulant clotting factors in plasma
Plasminogen
TFPI
Proteins C and S
Antithrombin
Differentiate the composition and site of red and white thrombi
Red = high fibrin component, forms within veins White = high platelet component, forms within atherosclerotic plaque
What is the main risk associated with red thrombi?
Life-threatening emboli
What is the main risk associated with white thrombi?
Plaque rupture to release thrombus into arterial lumen and cause ischaemia
Recall the triad of factors that lead to thrombus production
- Low rate of blood flow
- Consistency of blood
- Vessel wall integrity
How does blood flow rate affect risk of thrombus production?
Anticoagulant factors are not replenished due to stagnant flow
What does the term “consistency” refer to in the blood?
Balance of pro- and anti-coagulant factors (NOT viscosity)
Give an example of a disorder that result in high consistency of blood
Factor V Leiden - it cannot be inactivated by the normal factor V-deactivating processes
What drugs are used to combat thrombus production?
Anti-coagulants
What are the 2 main CVD disease states associated with venous pathology?
DVT
PE
What are the 2 main CVD disease states associated with arterial pathology?
Stroke
Acute coronary syndrome
Aortic aneurysm
AF
