Haem: Coagulation Flashcards
List some pro-coagulant factors in the body.
- Platelets
- Endothelium
- vWF
- Coagulation cascade
List some anti-coagulant factors in the body.
- Fibrinolysis
- Anti-thrombins
- Protein C/S
- Tissue factor pathway inhibitor
Which three responses are stimulated by vessel injury?
- Vasoconstriction
- Platelet activation (forms primary haemostatic plug)
- Activation of the coagulation cascade
What are the components of blood clot formation?
- Vascular endothelium
- Platelets
- Coagulation factors
- White blood cells
What are the two main functions of the endothelium?
- Synthesis of prostcyclin, vWF, plasminogen activators and thrombomodulin
- Maintain barrier between blood and pro-coagulant subendothelial structures
How many platelets are produced by each megakaryocyte?
4000
What is the life span of platelets?
10 days
NOTE: this is important because it means that the effect of antiplatelet drugs lasts for 10 days after stopping the drug
What are glycoproteins?
Cell surface proteins through which platelets can interact with the endothelium, vWF and other platelets
What do dense granules contain?
Energy stores (ATP and ADP)
Which features of platelets enable them to massively expan their surface area?
Open cannalicular system and microtubules and actomyosin
What are the two ways in which platelets can adhere to sub-endothelial structures?
DIRECTLY - via GlpIa
INDIRECTLY - via binding of GlpIb to vWF (this is MORE IMPORTANT)
which factors, released by platelets after adhesion, promote platelet aggregation?
ADP
Thromboxane A2
How do platelets bind to each other?
GlpIIb/IIIa
It also binds to fibrinogen via this receptor
Describe the effects of aspirin and other NSAIDs on the arachidonic acid pathway.
Aspirin is an irreversible COX inhibitor
Other NSAIDs reversibly inhibit COX
What is the rate-limiting step for fibrin formation?
Factor 10a
What are the effects of thrombin formation?
- Activates fibrinogen
- Activates platelets
- Activates profactors (factor 5 and 8)
- Activates zymogens (factor 7, 11 and 13)
Name the complex that is responsible for activating prothrombin to thrombin.
Prothrombinase complex
Outline the initiation phase of the clotting cascade.
- Damage to the endothelium results in exposure of tissue factor which binds to factor 7 and activates it to factor 7a
- The tissue factor-factor 7a complex then activates factors 9 and 10
- Factor 10a binds to factor 5a resulting in the first step of the coagulation cascade
Outline the amplification phase of the clotting cascade.
- Activated factors 5 and 10 will result in the production of a small amount of thrombin
- This thrombin will activate platelets
- Thrombin will also activate factor 11 which activates factor 9
- Thrombin also activates factor 8 and recruits more factor 5a
- Factors 5a, 8a and 9a will bind to the activated platelet
Outline the propagation phase of the clotting cascade.
- Activated factors 5, 8 and 9 will recruit factor 10a
- This results in the generation of a large amount of thrombin (thrombin burst)
- This enables the formation of a stable fibrin clot
Why is the prothrombinase complex important?
It allows activation of prothombin at a much faster rate
What is required for adequate production/absorption of vitamin K?
- Bacteria in the gut produce Vitamin K
- It is fat-soluble so bile is needed for viatmin K to be absorbed
What is the most common cause of vitamin K deficiency?
Warfarin
Name two factors that convert plasminogen to plasmin.
- Tissue plasminogen activator
- Urokinase
Name a factor that inhibits the tissue plasminogen activator and urokinase.
Plasmingoen activtor inhibitor 1 and 2
Name two factors that directly inhibit plasmin.
- Alpha-2 antiplasmin
- Alpha-2 macroglobulin
What is the role of thrombin-activatable fibrinolysis inhibitor (TAFI)?
Inhibitor of fibrin breakdown