Haemostasis Flashcards
What is Haemostasis?
The process in which blood coagulation is initiated and terminated in a tightly regulated fashion together with the removal of the clot
What is the first step of haemostasis?
Vasoconstriction restricts blood flow to the vessel
What is primary haemostasis?
The second stage, platelet aggregation that forms a plug
What is secondary haemostasis?
Generation of the enzyme thrombin that converts soluble fibrinogen to insoluble fibrin
What is Fibrinolysis?
Removal of the clot
What is the haemostatic system?
a mosaic of activating or inhibitory pathways
What are the five major components of the haemostatic system?
Blood vessels
– Platelets
– Coagulation factors
– Coagulation inhibitors
– Fibrinolytic factors (clot dissolving components)
Why must haemostasis be regulated?
to prevent inappropriate clot formation
What can happen when blood vessels are blocked?
Restricting blood flow
Starving tissues of oxygen
Leading to cell death
Where are platelets produced?
In the bone marrow
Where are coagulation proteins produced?
Primarily made in the liver
Why is haemostasis so rapid?
all the components are pre-synthesised and circulating in the blood
How do activated platelets generate thrombin?
they expose a surface that promotes the assembly of complexes leading to local generation of thrombin
What does the undisturbed endothelium present?
An anticoagulant response that dampens the activation of coagulation
What does the anticoagulant response do?
limits spread of the response beyond the injury
Where are platelets produced?
Bone marrow
What is Thrombopoietin?
Glycoprotein that regulates the production of platelets
What is thrombocytopenia?
Deficiency in circulating platelets due to decreased platelet formation
What are megakaryocytes?
hematopoietic cells that are responsible for the production of platelets
What is the purpose of the adhesion molecules found on the surface
To recognise components in the matrix e.g collagen and VWF
What occurs when platelets bind to ligands? (such as collagen)
release of granules containing ADP and thromboxane that activates the platelet
What does the exposure of phosphotidylserine (PS) on the platelet surface lead to?
The negatively charged surface promotes thrombin generation and fibrin deposition
What occurs to VWF under sheer stress?
It unfolds, exposing platelet binding sites. These can then bind to platelets as they go past
What does localised thrombin generation lead to?
further platelet activation and formation of a polymerised fibrin mesh
What are zymogens?
serine proteases that travel in the blood and require cofactors to work effectively, they help assemble blood clots
What is a tissue factor?
the trigger for blood coagulation, it’s a cell surface protein expressed on cells not in contact with the blood
What is the initiation stage of the pro-coagulant response?
Vascular damage means that blood is then exposed to cells that express tissue factors, this then amplifies the volume of thrombin produced which can convert fibrinogen to fibrin
What are some ways we can control the activation mechanism?
1) Shutting down the initiation complex after it has been activated
2) Reducing cofactors and activated proteases which reduces the generation of fibrin clots
What is TFP1?
a protein that inactivates the initiation complex
How can you do a lab assessment of clotting?
Centrifuge to prepare the plasma, then add Calcium to initiate clotting
What is thrombosis?
The formation of an intravascular clot
What does sweet clover poison do?
It is a competitive inhibitor of vitamin K, so prevents blood from clotting after an injury
What are some treatments for blood loss?
Salt solution can expand the blood volume, or replace platelets/ cofactors/ coagulation factors
What does Virchows triad explain?
explains pathophysiologic mechanisms leading to thrombosis
How would liver disease have an effect on platelet production?
Platelet formation is regulated by the
hormone thrombopoietin produced by the
liver and kidney
How does the autocrine effect of platelet activation work?
The platelet contains adhesion molecules that bind to VWF in the blood
the binding causes the release of ADP and thromboxane into the blood causing the platelet to become activated in an autocrine fashion
Where is VWF found?
it is found in the broken endothelium (collagen of the skin)
What does the exposure of the negatively charged surface on the platelet promote?
it promotes thrombin generation and fibrin deposition
What kind of disease is VWF disease?
autosomal recessive
How would you distinguish an activated factor?
has a small an next to its roman numerals
Is the extrinsic or intrinsic coagulation pathway activated by tissue factor?
extrinsic
How does the anticoagulant response work?
in terms of thrombin
Thrombin binds to thrombomodulin which activates the anticoagulant pathway
This then activates protein C which in turn with protein S rapidly inactivates both factor 8 and factor 5
