Haemostasis Flashcards
(40 cards)
What is haemostasis?
Cessation of bleeding after injury to minimise blood loss
What is the sequence of events involved in haemostasis?
Vascular Injury Vasoconstriction Platelet plug formation Coagulation (blood clotting) Stabilisation of the clot Fibrinolysis (removal of clots)
Why does haemostasis need to be carefully regulated?
Inability to clot can result in extreme hemorrhage.
Propensity to clot can result in thrombosis, which can mobilise (embolism).
What are platelets derived from?
Fragments of megakaryocytes. (large bone marrow cell)
How many platelets are in the blood, and what is their lifespan?
4x10^8, 8-10 days
What do platelets consist of?
No nuclei, most normal organelles
How to platelets adhere to the endothelium?
Bind to vWF (von willebrand factor) present on the basement membrane.
How do platelets aggregate to eachother?
Fibrinogen bridges, binding to GPIIb and GPIIa integrin receptors.
What causes vessel smooth muscle to contract (vascular spasm)?
Initially, local sympathetic pain receptor reflex.
Endothelium derived factors and platelet released factors (thromboxane A2, serotonina and ADP)
What is a platelet plug?
Platelets adhere to damaged endothelium to form a platelet plug.
How does a platelet plug form?
Von Willebrand factor (vWF), secreted which causes platelet adherence to endothelium.
Express glycoprotein receptors (GPII) that interact with other platelets, via fibrinogen bridges that stabilise platelet aggregates.
How do platelets promote further clotting after initial plug?
Platelets release cytoplasmic granules such as adenosine diphosphate (ADP), serotonin and thromboxane. Attracts more platelets to the affected area, vasoconstrict and assist in platelet aggregation.
Continuing the process in a positive feedback loop.
What is the coagulation cascade and what is its final reaction?
Clotting factors (inactive plasma serine proteases) are activated in a sequence of events known as ‘coagulation cascade’ which leads to the formation of Fibrin from inactive fibrinogen plasma protein (zymogen).
How does fibrin produce a clot?
Fibrin mesh produced that traps blood cells and causes hardening of primary plug.
What are the two pathways of of haemostasis and what stimulates each?
Intrinsic - activation of factor XII by certain negatively charged surfaces, such as collagen.
Extrinsic - trauma leading to release of tissue factor activating VII to VIIa
Why is the intrinsic pathway a problem clinically?
Can lead to coagulation following heart valve replacement
What is the common clotting cascade (shared by both pathways)?
Conversion of factor X to active Xa which catalyses the conversion of inactive prothrombin (factor II) to active thrombin (factor IIa) which polymerises soluble fibrinogen (factor I) into insoluble fibrin (factor I a) strands.
Fibrin strands form mesh around platlet plug to trap other blood cells
Fibrin cross linked - stabilised by factor XIIIa (fibrin stabilising factor)
How does soluble fibrinogen get converted into insoluble fibrin?
Removal of negatively charged fibrinopeptides
What is the independent extrinsic cascade?
Trauma converts VII to VIIa which along with TF catalyses the formation of Xa from X
What is the independent intrinsic cascade?
Surface leads to conversion of XII to XIIa, which converts XI to XIa which converts IX to IXa. Along with VIIIa, IXa converts X to Xa.
What does factor XIII do?
Factor XIII, which forms covalent bonds that stabilise and crosslink the fibrin polymers.
Where does the cascade occur?
On the platelet surface
Which factors are localised to the platelet surface?
Va and Xa
How is there a feed-forward loop in haemostasis?
Thrombin converts factor X to Xa, this along with factor V can convert prothrombin to thrombin
