Flashcards in Basic Haemostasis Deck (23)
What are the two main mechanisms involved in haemostasis?
Platelets and Clotting Cascade
What happens in primary and secondary haemostasis?
Primary - platelet activation and aggregation - formation of an unstable platelet plug
Secondary - stabilisation of the plug with fibrin
The process by which blood is converted from a liquid to a solid.
What cells secrete Von Willebrand Factor?
Endothelial cells and platelets
What is exposed when the endothelial layer is damaged?
Subendothelial layer - collagen
How can the subendothelial layer be recognised?
The Von Willebrand factors bind to the collagen and the GlpIb receptors on the VWF bind to platelets
GlpIa receptors on the platelets can bind directly to the collagen
When the platelets are activated what do they release?
ADP and prostaglandins
What receptors become available on the platelets to allow fibrinogen to bind?
GlpIIa and GlpIIIb
Describe the effect of thrombin on the formation of the primary platelet plug.
Thrombin stimulates the activation of platelets so that they aggregate.
Describe the changes in the morphology of the platelets that take place when they are activated.
The platelets become more spiculated and their membrane changes composition. Phospholipids that were on the inside of the membrane move to the outside, which is important because they bind to coagulation factors. The platelets express GlpIIa and GlpIIIb receptors that can bind to fibrinogen.
Where are clotting factors, fibrinolytic factors and inhibitors synthesised?
Mainly in the LIVER
Von Willebrand Factor is produced in high concentration by the endothelial cells
Factor V is produced by megakaryocytes
Which factors are cofactors?
Factor 8 and Factor 5
Describe the extrinsic pathway.
The extrinsic pathway is activation of factor 10 to 10a by Tissue factor bound to Factor 7 and calcium. This is the normal physiological activation of the clotting cascade.
What are factor 1 and factor 2 more commonly called?
Factor 1 = Fibrinogen ---> Fibrin
Factor 2 = Prothrombin ---> Thrombin
What protein breaks down fibrin clots and what is its precursor? How is it activated?
Plasmin - the precursor is plasminogen
Plasminogen is converted to plasmin by the action of Tissue Plasminogen Activator (tPA)
tPA doesn't usually come into contact with plasminogen but when a fibrin clot forms, it assembles tPA and plasminogen on its surface so they come into contact and plasminogen is converted to plasmin.
What products can be given in therapeutic thrombolysis of myocardial infarction?
tPA (tissue plasminogen activator) and bacterial activator streptokinase
What are the two main coagulation inhibitory mechanisms?
DIRECT inhibition - antithrombin
INDIRECT inhibition - Protein C inhibition pathway
What factors are inhibited by antithrombin?
Factor 2a, 9a, 10a and 11a
It is a broad scale clotting factor inhibitor
Describe the effect of heparin.
Heparin accelerates the action of antithrombin
What are factor 8 and factor 5 activated by?
Trace amounts of thrombin
Describe the protein C inhibitory pathway.
Thrombin, once produced is usually involved in clot formation, activating platelets and activating factor 8 and factor 5.
Thrombin can binds to thrombomodulin (a protein on the surface of the endothelium) which changes its specification.
It then activates Protein C and Protein S, which then inactivate Factor 8 and Factor 5. This is the second anticoagulant mechanism.
What are the consequences of Factor V Leiden?
Factor V Leiden is a common polymorphism in the population. Factor V Leiden can't be inactivated as well as wild type Factor V. If protein C can't inactivate the factor V leiden as well, there is increased risk of thrombosis.