Haemostasis Flashcards
What does the balance of haemostasis depend on?
The balance between coagulation factors which cause a clot and fibrinolytic factors which break the clot down
What are the three stages of haemostasis?
Vasoconstriction
Formation of an unstable platelet plug
Formation of a stable fibrin clot
Then fibrinolysis - the breakdown of the cloth
Describe the vasoconstriction stage of haemostasis?
-Endothilins released from endothelial lining of blood vessels
-bind to specific receptors on smooth muscle of vessel
-cause it to contract
- vasoconstriction
-reduced release of nitric oxide and prostaglandins
What two chemicals normally found in the blood are involved in ensuring the blood remains thin under normal conditions?
Nitric oxide and prostacyclin
Describe how a unstable platelet plug forms?
Platelets bind directly to exposed collagen
VwF is released - this binds to platelets using the GP1b receptor, causing the platelets to become activated and release alpha and beta granules after changing shape from disc to rounded with spicules to encourage aggregation. These granules contain ADP, Thromboxane A2 and Serotonin amongst other chemicals, which results in the platelets aggregating at the site of injury - positive feedback response.
What does ADP and Thromboxane A2 lead to?
They bind to P2Y12 receptors and Thromboxane A2 receptors and cause further platelet aggregation, activation and adhesion
What does an exposed GP GP IIb/IIIa receptor lead to?
Allows the platelets to bind to fibrinogen, linking the platelets together to form a platelet plug
What is prostacyclin?
A vasodilator which circulates in the blood to ensure that inappropriate platelet aggregation does not occur
How does aspirin work?
Binds to COX enzyme which inhibits Thromboxane A2 production therefore less platelet aggregation
What type of drug is clopidogrel and how does it work?
Antiplatelet drug - works by binding to and therefore blocking ADP’s P2Y12 receptor
How long do the effects of clopidogrel last for?
7 days
Describe the intrinsic coagulation cascade
12 to 12a 11 to 11a 9 to 9a 8 to 8a 10 to 10a 10 reacts with 5 and 4 (calcium ions) to form 2 2 to 2a (prothrombin to thrombin) 1 to 1a (fibrinogen to fibrin)
Which clotting factors are affected by vitamin K?
2, 7, 9 and 10
Describe the extrinsic coagulation cascade?
Tissue factor exposed by endothelial cells activated factor 7 to make factor 10, and also increase production of factor 9
What happens in the initiation stages?
The production of a small amount of thrombin via the extrinsic pathway allows the coagulation factors 5 and 8 of the intrinsic pathway to be activated
Describe how protein C and protein S affect coagulation
Thrombin binds to thrombomodulin on the surface of the endothelial cells, which causes Protein C to become activated = APC
APC causes the inactivation of factors 8a and 5a
What does antithronbin inactivate?
Factor 10a and thrombin
What protein is needed for protein C to become activated?
Protein S
What does factor 13 do in the coagulation cascade?
Cross links fibrin molecules so that the fibrin clot can become more stable
How does Heparin work?
Heparin works indirectly by potentiating the action of antithrombin leading to the inactivation of factors Xa and IIa (thrombin).
How is heparin administered?
By IV or subcutaneously
What are DOACs and how do they work?
Direct Oral Anti Coagulants - work by blocking factor 10a and 2a without involving antithrombin
How does Warfarin work?
It is a vitamin K antagonist, meaning it decreases the production of vitamin K dependent factors in the liver, so 2, 7, 9 and 10
What process does Vitamin K antagonists interfere with?
Gamma carboxylation - needed for the production of factors 2, 7, 9 and 10
What is the difference in the time taken for effect to come about between heparin and warfarin?
Heparin effect is immediate, warfarin we wait, effect takes some time
How does the plasminogen / plasmin system work?
Plasminogen and t-Pa binds to lysine residue on fibrin, which activates it to form plasmin. Plasmin breaks down fibrin into fibrin-degradation products