Haemostasis Flashcards
What 2 problems can abnormal haemostats cause
- Bleeding disorders
2. Thrombosis
4 steps in the response to injury of endothelial lining
Vessel constriction
Formation of an unstable platelet plug
Stabilisation of the plug with fibrin
Vessel repair and dissolution of clot
where are procoagulants found in a vessel wall
Below the initial single cell endothelial layer
What is the primary initiator of the coagulation cascade
Tissue factor
Where is tissue factor found
On some of the vascular smooth muscle cells below the endothelial layer of a vessel wall
Vessel constriction is more important in X blood vessels
small
Platelets are derived from X which are the largest cells in the bone marrow.
megakaryocytes
megakaryocytes are X hence the large nucleus.
polyploidy
There is a small source of megakaryocytes from the X.
lungs
How do megakaryocytic physically become platelets
Platelets bleb off the megakaryocyte off finger-like structures.
What granules are within platelets and what do they contain (2, 4 and 2)
α-granule (GF’s, fibrinogen, FV and VWF), dense granules (ADP and ATP help augment functions of surrounding platelets when secreted)
what helps the platelet adopt its shape when active.
The actomyosin and microtubules
4 roles of platelets?
Haemostasis and thrombosis, cancer
atherosclerosis
infection
inflammation
How does VWF help with platelet activation
VWF circulates
Vascular injury exposes subendothelial matrix containing collagen, which binds VWF via its exposed collagen binding sites.
This causes VWF to transition from folded globular form to extended linear polypeptide form by the shear forces of blood
This reveals platelet binding sites
The platelets are recruited and bind to VWF through Gp1b.
What activates VWF
Collegen exposure
When and where and through what receptors do platelets bind to collagen
using Gp6 and α2β2 but this can only happen in low shear conditions (in veins)
What 3 things can activate a platelet
Collagen
VWF
Thrombin
What happens when a platelet is activated
When activated the platelet releases its granules, changes their shape and change the composition of their phospholipid surface.
In the granules are ADP and thromboxane that are released in a cloud and prime more platelets that travel near that cloud causing them to aggregate.
How do platelets aggregate (receptor and molecule)
Intergrin α2bβ3 binds fibrinogen and cross links platelets together and causes them to aggregate
Platelet count normal is between XXXXX x10^9/litre.
150-400
What platelet count leads to spontaneous bleeding
less than 40
What platelet count can lead to purpura
below 10
what is the key role of thrombin
to cleave fibrinogen to leave sticky fibrin
where are the majority of clotting factors produced
Liver
